US 201400.52264A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0052264 A1 Hufen et al. (43) Pub. Date: Feb. 20, 2014

(54) POROUS, STABILIZED Publication Classification CRANOMAXILLOFACIAL MPLANTS AND METHODS AND KITS RELATING THERETO (51) Int. Cl. A6IF 2/28 (2006.01) (71) Applicant: Ticona LLC, Florence, KY (US) (52) U.S. Cl. CPC ...... A61F 2/2803 (2013.01) (72) Inventors: Julia Hufen, Rheinberg (DE); Anthony USPC ...... 623/17.17; 264/118 Verrocchi, Covington, KY (US); Rainer Walkenhorst, Melle (DE) (57) ABSTRACT Porous craniomaxillofacial implants may include a plurality of polymeric particles sintered together at a plurality of con (73) Assignee: Ticona LLC, Florence, KY (US) tact points to form a porous network having pores; and an antioxidant disposed on a surface of at least some of the (21) Appl. No.: 13/964,756 polymeric particles and/or in the pore of the porous network, So as to stabilize the implants from at least some oxidative (22) Filed: Aug. 12, 2013 damage during storage, transportation, and/or implementa tion (in vivo and/or ex vivo). Preferably, the polymeric par ticles include at least one of polyethylene, a polyethylene Related U.S. Application Data polypropylene copolymer, a polyethylene-polybutylene (60) Provisional application No. 61/684.937, filed on Aug. copolymer, polytetrafluoroethylene, and expanded polytet 20, 2012. rafluoroethylene.

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POROUS, STABILIZED comprising heating a plurality of polymeric particles in a CRANOMAXILLOFACIAL MPLANTS AND mold so as to sinter together the polymeric particles at a METHODS AND KITS RELATING THERETO plurality of contact points thereby forming a porous network, the plurality of polymeric particles comprising polyethylene; BACKGROUND and contacting the polymeric particles with an antioxidant. 0009. Yet another embodiment of the present invention 0001. The present invention relates to porous craniomax may provide for a method of forming a porous implant, the illofacial implants stabilized with antioxidants, and methods method comprising heating a plurality of polymeric particles and kits relating thereto. in a mold so as to sinter together the polymeric particles at a 0002 Surgeons often repair or augment bone structures in plurality of contact points thereby forming a porous network, reconstructive Surgeries that may be necessitated by injury or the plurality of polymeric particles comprising at least one birth defects. While natural bone from the patient is a pre polymer selected from the group consisting of a polyethyl ferred material for repairing bone structure, in craniomaxil ene-polypropylene copolymer, a polyethylene-polybutylene lofacial repair and augmentation, natural bone may not be copolymer, polytetrafluoroethylene, and expanded polytet practical. As it is not easy to reshape bone, the bone graft is rafluoroethylene; and contacting the polymeric particles with often matched in size and shape to the area that needs to be an antioxidant. repaired. Finding Such a match is often difficult, and some 0010. Another embodiment of the present invention may times impossible, given the contours of the various areas of provide for a method for structurally modifying a portion of a the craniomaxillofacial area. Accordingly, a craniomaxillo cranium, the method comprising implantingaporous Surgical facial bone graft can leave deformed features that could implant into a cranium, the porous Surgical implant compris require further Surgery to repair. ing: a porous structure formed from a plurality of polymeric 0003) Synthetic materials have been used as an alternative particles sintered at a plurality of contact points, the plurality to bone grafts. One of the more common synthetic materials of polymeric particles comprising polyethylene, and an anti in craniomaxillofacial repair and augmentation is high-den oxidant. sity polyethylene, and is often utilized as a porous structure 0011. Another embodiment of the present invention may having high surface area to allow for fibroblast intergrowth. provide for a method for structurally modifying a portion of a 0004. The advantages often touted in regards to the use of cranium, the method comprising implantingaporous Surgical ultrahigh molecular weight polyethylene include the chemi implant into a cranium, the porous Surgical implant compris cal stability, no donor site morbidity, and availability. How ing: a porous structure formed from a plurality of polymeric ever, recent studies have shown that after implantation poly particles sintered at a plurality of contact points, the plurality ethylene slowly undergoes oxidation at the Surface, which of polymeric particles comprising at least one polymer causes the polyethylene to become brittle, which can lead to selected from the group consisting of a polyethylene wear of the implants, and abrasion of Surrounding tissue polypropylene copolymer, a polyethylene-polybutylene and/or bone. Consequently, in Some instances, the implant copolymer, polytetrafluoroethylene, and expanded polytet may need to be replaced, which can involve additional Sur rafluoroethylene, and an antioxidant. geries with potential complications. The consequences of 0012. The features and advantages of the present invention polyethylene oxidation may be magnified in craniomaxillo will be readily apparent to those skilled in the art upon a facial implants as the high Surface area of the porous structure reading of the description of the preferred embodiments that provides for a greater percentage of the implant to become follows. brittle. BRIEF DESCRIPTION OF THE DRAWINGS SUMMARY OF THE INVENTION 0013 The following figures are included to illustrate cer 0005. The present invention relates to porous craniomax tain aspects of the present invention, and should not be viewed illofacial implants stabilized with antioxidants, and methods as exclusive embodiments. The subject matter disclosed is and kits relating thereto. capable of considerable modifications, alterations, combina 0006. One embodiment of the present invention may pro tions, and equivalents in form and function, as will occur to vide for a porous implant that comprises a plurality of poly those skilled in the art and having the benefit of this disclo meric particles sintered together at a plurality of contact SUC. points to form a porous network having pores, the plurality of 0014 FIGS. 1A-B provide illustrative scanning electron polymeric particles comprising polyethylene; and an antioxi micrographs of polyethylene particles described herein hav dant disposed on a surface of at least Some of the polymeric ing popcorn shapes and potato shapes, respectively. particles and/or in the pore of the porous network. 0015 FIG. 2 provides an illustrative scanning electron 0007 Another embodiment of the present invention may micrograph of polyethylene particles bound together where provide for a porous implant that comprises a plurality of the polyethylene particles have a Surface roughness that is polymeric particles sintered together at a plurality of contact about nano-rough to about micro-rough. points to form a porous network having pores, the plurality of 0016 FIG. 3A illustrates an example of a porous implant polymeric particles comprising at least one polymer selected of the present invention being placed in a cranium as a cranial from the group consisting of a polyethylene-polypropylene implant. copolymer, a polyethylene-polybutylene copolymer, polytet 0017 FIG. 3B illustrates a more detailed view of a cranial rafluoroethylene, and expanded polytetrafluoroethylene; and implant of 3A including an adhesive. an antioxidant disposed on a Surface of at least Some of the 0018 FIG. 4A illustrates an example of a porous implant polymeric particles and/or in the pore of the porous network. of the present invention as an orbital reconstruction implant. 0008 Another embodiment of the present invention may 0019 FIG. 4B illustrates a cross-section of a orbital recon provide for a method of formingaporous implant, the method struction implant FIG. 4B. US 2014/0052264 A1 Feb. 20, 2014

0020 FIG.4C illustrates an example of a reinforcing mesh the shape of crystals), and any hybrid thereof, and the like that includes securing components. with rounded corners and/or edges. Illustrative examples of 0021 FIG. 5 illustrates an example of a porous implant of popcorn shapes and potato shapes are provided in FIGS. the present invention being placed as a mandible implant. 1A-B, respectively. 0029. In preferable embodiments, a polymeric particulate DETAILED DESCRIPTION may comprise at least one polymer selected from the group of 0022. The present invention relates to porous craniomax polyethylene, polyethylene-polypropylene copolymers, illofacial implants stabilized with antioxidants, and methods polyethylene-polybutylene copolymers, polytetrafluoroeth and kits relating thereto. ylene, or expanded polytetrafluoroethylene. 0023 The present invention provides for, in some embodi 0030 Polymeric particles suitable for use in conjunction ments, porous implants that comprise a plurality of polymeric with porous implants of the present invention may comprise particles sintered together at a plurality of contact points so as high to ultrahigh molecular weight polymers of the compo to form a porous network and an antioxidant adsorbed to the sitions described herein. As used herein, the use of “high to Surface of at least a portion of the polymeric particles. As used ultrahigh molecular weight polymer should be taken to herein, the term “sintered, and the like, refers to a physical encompass high molecular weight polymer, very-high connection that bonds two particles together. The bonds molecular weight polymer, ultrahigh molecular weight poly between two sintered particles may be rigid or flexible mer, and any blend thereof. As used herein, the term “high depending on at least the composition of the polymeric par molecular weight polymer refers to a polymer composition ticles. The bonding may or may not also involve chemical having an average molecular weight of about 300,000 g/mol bonding. In preferable embodiments, a polymeric particulate to about 1,000,000 g/mol. As used herein, the term “very-high may comprise at least one polymer selected from the group of molecular weight polymer refers to a polymer composition polyethylene, polyethylene-polypropylene copolymers, having an average molecular weight of about 1,000,000 polyethylene-polybutylene copolymers, polytetrafluoroeth g/mol to about 3,000,000 g/mol. As used herein, the term ylene, or expanded polytetrafluoroethylene. “ultrahigh molecular weight polymer refers to a polymer 0024. Without being limited by theory, it is believed that composition having an average molecular weight of about the antioxidant may mitigate and/or slow the oxidation of the 3,000,000 g/mol to about 20,000,000 g/mol. polymeric particles of the implant, thereby extending the 0031. In some embodiments, polymeric particles suitable lifetime of the implant. for use in conjunction with porous implants of the present 0025. Further, the porous network of the porous implant invention may comprise high to ultrahigh molecular weight may enable infiltration of a patient’s cells into the porous polymer having an average molecular weight ranging from a implant, which may lead to vascularization and tissue growth lower limit of about 300,000 g/mol, 500,000 g/mol, 1,000, in and around the porous implant, and consequently mitigate 000 g/mol, 2,000,000 g/mol, 3,000,000 g/mol, or 5,000,000 implant rejection by the patient. g/mol to an upper limit of about 20,000,000 g/mol, 15,000, 0026. It should be noted that when “about” is provided 000 g/mol, 12,000,000 g/mol, 10,000,000 g/mol, 9,000,000 herein at the beginning of a numerical list, “about modifies g/mol, 5,000,000 g/mol, 3,000,000 g/mol, or 1,000,000 each number of the numerical list. It should be noted that in g/mol, and wherein the average molecular weight may range Some numerical listings of ranges, some lower limits listed from any lower limit to any upper limit and encompass any may be greater than Some upper limits listed. One skilled in range therebetween. Methods suitable for measuring the the art will recognize that the selected subset will require the molecular weight of polymers described herein include selection of an upper limit in excess of the selected lower ASTM D4O2O. limit. 0032 Polyethylene particles suitable for use in conjunc 0027 Porous implants of the present invention may, in tion with porous implants of the present invention may, in Some embodiments, comprise a plurality of polymeric par Some embodiments, include, but are not limited to, commer ticles sintered together at a plurality of contact points so as to cially available GURR) (ultrahigh molecular weight polyeth form a porous network, and an antioxidant adsorbed to a ylene, available from Ticona Polymers LLC). Specifically, Surface of at least a portion of the polymeric particles. It GURR) polymers may include: GUR(R) 1020, GUR(R) 1050, should be noted that if the antioxidant is relatively solid, it GURR) 2000 series (2105,2122, 2122-5, 2126), GURR4000 will most likely be present on the surface of at least a portion series (4113, 4120, 4130, 4150, 4152 4170, 4012, 4122-5, of the polymeric particles. On the other hand, if the antioxi 4022-6, 4050-3/4150-3), GUR 8000R series (8110, 8020), dant is a liquid, it also is on the Surface of at least a portion of GURR X series (X143, X184, X168, X172, X192, X198), the polymeric particles, but can diffuse over time through the and the like, any derivative thereof, and any combination pores of the porous network. Thus, in some embodiments, thereof. These are all available from Ticona Polymers LLC. porous implants of the present invention may comprise anti 0033 Polytetrafluoroethylene particles suitable for use in oxidants adsorbed to the surface of at least some of the poly conjunction with porous implants of the present invention meric particles and also antioxidants disposed in the pores of may, in some embodiments, include, but are not limited to, the porous network. commercially available POLYFLONTM and POLYFLONTM 0028. It should be understood that as used herein, the M-Series (available from Daikin), TEFLONR) (available terms “particle' and “particulate' may be used interchange from DuPont), DYNEONTM PTFE (available from 3M), ably and include all known shapes of materials, including ALGOFLONR) (available from Solvay), and the like, any spherical, ovular, Substantially spherical, Substantially ovu derivative thereof, and any combination thereof. lar, prolate spheroidal, popcorn, Substantially popcorn, 0034 Polypropylene particles suitable for use in conjunc potato, Substantially potato, discus, platelet, flake, ligamen tion with porous implants of the present invention may, in tal, acicular, fibrous, polygonal (such as cubic), randomly Some embodiments, include, but are not limited to, commer shaped (such as the shape of crushed rocks), faceted (such as cially available ExxonMobiltM polypropylene resin (avail US 2014/0052264 A1 Feb. 20, 2014

able from ExxonMobil), PURELLTM (available from Lyon thereof. By way of nonlimiting example, a porous implant of dellBasell), MOPLENR) (available from LyondellBasell), the present invention may comprise a plurality of polymeric SABIC(R) PP (available from Saudi Basic Industries Corpo particles having a multimodal diameter distribution. For ration), and the like, any derivative thereof, and any combi example, a bimodal diameter distribution derived from a mix nation thereof. ture of a first plurality of polymeric particles having an aver 0035. In some embodiments, the polymeric particles suit age diameter of about 50 microns and a second plurality of able for use in conjunction with porous implants of the polymeric particles having an average diameter of 500 present invention may have a diameter in at least one dimen microns. sion ranging from a lower limit of about 10 microns, 50 0041. By way of another nonlimiting example, a porous microns, 100 microns, 150 microns, 200 microns, and 250 implant of the present invention may comprise a first plurality microns to an upper limit of about 5000 microns, 2000 of polymeric particles comprising high molecular weight microns, 1000 microns, 750 microns, 500 microns, 400 polymer and a second plurality of polymeric particles com microns, 300 microns, 250 microns, 200 microns, 150 prising ultrahigh molecular weight polymer. By way of yet microns, or 100 microns, and wherein the diameter in at least another nonlimiting example, a porous implant of the present one dimension may range from any lower limit to any upper invention may comprise a first plurality of polymeric particles limit and encompass any range therebetween. comprising high molecular weight polymer having a substan 0036. In some embodiments, the polymeric particles suit tially potato shape and a second plurality of polymeric par able for use in conjunction with porous implants of the ticles comprising ultrahigh molecular weight polymer having present invention may have a bulk density ranging from a a Substantially popcorn shape. lower limit of about 0.10 g/cm, 0.25 g/cm, or 0.5 g/cm to an 0042. By way of another nonlimiting example, a porous upper limit of about 0.9 g/cm, 0.75 g/cm, or 0.5 g/cm, and implant of the present invention may comprise a first plurality wherein the bulk density may range from any lower limit to of polytetrafluoroethylene particles and a second plurality of any upper limit and encompass any range therebetween. polyethylene particles. By way of yet another nonlimiting 0037. In some embodiments, the polymeric particles suit example, a porous implant of the present invention may com able for use in conjunction with porous implants of the prise a first plurality of polytetrafluoroethylene particles and present invention may have a Surface roughness that is about a second plurality of expanded polytetrafluoroethylene par nano-rough to about micro-rough. As used herein the term ticles. By way of another nonlimiting example, a porous “micro-rough' refers to a surface having features that extend implant of the present invention may comprise a first plurality about 0.5 microns to about 20 microns from the Surface. As of polyethylene particles and a second plurality of expanded used herein, the term “nano-rough refers to the surface hav polytetrafluoroethylene particles. By way of another nonlim ing features that extend about 1 nm to about 500 nm from the iting example, a porous implant of the present invention may surface. FIG. 2 provides a nonlimiting illustration of polyeth comprise a first plurality of polyethylene particles, a second ylene particles bound together where the polyethylene par plurality of polytetrafluoroethylene particles, and a third plu ticles have a surface roughness that is about nano-rough to rality of expanded polytetrafluoroethylene particles. It should about micro-rough. be noted that each plurality of particle may, in some embodi 0038. Without being limited by theory, it is believed that ments, differ from each other in more than their composition, Surface roughness may influence the ability for cells to grow e.g., particle size, roughness, and the like described herein. on the Surface of the polymeric particles, and consequently 0043. In some embodiments, the porous network of a infiltrate the porous network of a porous implant to improve porous implant of the present invention may comprise a plu implantation Success. Further, it is believed that nano-rough rality of pores. The dimensions of such pores may depend on, to micro-rough Surfaces may enhance cell growth on poly inter alia, the size of the polymeric particles, the size of the meric particles, thereby enhancing the biocompatibility and fusions between particles, the interstitial spaces between par mitigate patient rejection of the porous implants of the ticles, and any additives included in the porous implant. In present invention. It should be noted that Surface roughness is Some embodiments, pores of a porous network described preferably determined after formation of the porous implant herein may have an average diameter ranging from a lower as some embodiments of forming porous implants, as limit of about 15 microns, 25 microns, 50 microns, 100 described herein, include temperature and pressure changes microns, 150 microns, 200 microns, or 300 microns to an that may alter the Surface roughness of the polymeric par upper limit of about 500 microns, 400 microns, 300 microns, ticles. 250 microns, or 100 microns, and wherein the average diam 0039. In some embodiments, the polymeric particles suit eter may range from any lower limit to any upper limit and able for use in conjunction with porous implants of the encompass any range therebetween. present invention may have a Surface roughness with features 0044. In some embodiments, the porous network of a extending from the Surface in an amount ranging from a lower porous implant of the present invention may have a porosity limit of about 1 nm, 10 nm, 100 nm, 250 nm, 500 nm, 1 of about 40% to about 90%. The dimensions of such pores micron, or 2 microns to an upper limit of about 20 microns, 15 may depend on, interalia, the size of the polymeric particles, microns, 10 microns, 5 microns, 2 microns, 1 micron, 500 nm, the size of the fusions, and any additives included in the or 250 nm, and wherein the surface features may extend in an porous implant. amount range from any lower limit to any upper limit and 0045. In some embodiments, the porosity of the porous encompass any range therebetween. network may range from a lower limit of about 1%. 5%, 10%, 0040. In some embodiments, a porous implant of the 20%, 30%, 40%, 50%, or 60% to an upper limit of about 99%, present invention may comprise a mixture of two or more 90%. 80%, 70%, or 60%, and wherein the porosity may range polymeric particles distinguished by at least one of compo from any lower limit to any upper limit and encompass any sition, particle size, shape, morphology, additivation, aspect range therebetween. A lower porosity may exist if the porous ratio, bulk density, Surface roughness, and any combination implant has been compacted. US 2014/0052264 A1 Feb. 20, 2014

004.6 Antioxidants may, in Some embodiments, mitigate hydrochloride, adecypenol, adecypenol, adefovir, adelm oxidation and/or chemical degradation of the polymeric par idrol, ademetionine, adenosine, adinazolam, adipheinine ticles described herein during storage, transportation, and/or hydrochloride, adiposin, adoZelesin, adrafinil, adrenalone, implementation (in vivo and/or ex vivo). Examples of anti airbutamine, alacepril, alamecin, alanine, alaproclate, alap oxidants Suitable for use in conjunction with the porous tide, albendazole, albolabrin, albuterol (commercially avail implants of the present invention may, in Some embodiments, able as VENTOLINGR) from include, but are not limited to, anthocyanin, ascorbic acid, glutathione, lipoic acid, uric acid, resveratrol, flavonoids, car 0051 GlaxoSmithKline), albutoin, alclofenae, alclometa otenes (e.g., beta-carotene), carotenoids, tocopherols (e.g., Sone dipropionate, aluminum chlorhydroxyallantoinate alpha-tocopherol, beta-tocopherol, gamma-tocopherol, and (commercially available as ALCOLOXAR) from TRI-K delta-tocopherol), tocotrienols, ubiquinol, melatonin, sec Industries, Inc.), aldecalmycin, aldesleukin, aldioxa, alendr ondary aromatic amines, benzofuranones, hindered phenols, onate sodium (commercially available as FOSAMAX(R) from polyphenols, hindered amines, organophosphorus com Merck), alendronic acid, alentemol, alentemol hydrobro mide, aletamine hydrochloride, aleuronium chloride, alexi pounds, thioesters, benzoates, lactones, hydroxylamines, and dine, alfacalcidol, alfentanil hydrochloride, alfuzosin, alge the like, and any combination thereof. stone acetonide, alglucerase, alliflurane, alinastine, alipamide, 0047. In some embodiments, antioxidants may be allantoin, allobarbital, allopurinol, a tachy-kinins (TK) included in the porous implants of the present invention in an antagonist, alonimid, alosetron, alosetron hydrochloride, alo amount ranging from a lower limit of about 0.001%, 0.01%. Vudine, alpertine, alpha amylase, alpha idosone, alpidem, 0.05%, 0.1%, 0.5%, or 1% an upper limit of about 10%, 5%, alprazolam (commercially available as XANAX(R) from 3%, 2%, or 1% by weight of the polymer, wherein the amount Pfizer, Inc.), alprenolol hydrochloride, alprenoxime hydro may range from any lower limit to any upper limit and encom chloride, alprostadil, alrestatin Sodium, altanserin tartrate, pass any Subset therebetween. The amount of the antioxidants alteplase, althiazide, altretamine, altromycin B. alverinc cit may depend on a number of factors that include, interalia, the rate, alvircept Sudotox, amadinone acetate, amantadine application of the porous implant, the composition of the hydrochloride, ambamustine, ambomycin, ambruticin, antioxidant, the composition of the polymeric particles, and ambuphylline, ambuside, amcinafal, amcinonide, amdinocil any additional ingredients utilized in conjunction with the lin, amdinocillin pivoxil, amedalin hydrochloride, amelom porous implant (described further herein). etaSone, ameltolide, ameSergide, ametantrone acetate, ameZ 0048. In some embodiments, porous implants of the inium metilsulfate, amfebutamone, amfenac sodium, present invention may further comprises additives like active amflutizole, amicycline, amidephrine mesylate, amidox, pharmaceutical ingredients (APIs), growth factors, cells or amifloxacin, amifostine, amikacin, amiloride hydrochloride, cell-like structures, imaging agents, pigments and/or dyes, aminacrine hydrochloride, aminobenzoate potassium, ami and the like, and any combination thereof. It should be noted nobenzoate Sodium, aminocaproic acid, aminoglutethimide, that the term API encompasses prodrugs. aminohippurate Sodium, aminolevulinic acid, aminophylline, 0049 Porous implants of the present invention may, in aminorex, aminosalicylate Sodium, aminosalicylic acid, Some embodiments, comprise a plurality of polymeric par amiodarone, amiprilose hydrochloride, amiquinsin hydro ticles sintered together at a plurality of contact points so as to chloride, amisulpride, amitraz, amitriptyline hydrochloride, form a porous network, at least one antioxidant, and option amlexanoX, amlodipine, amobarbital sodium, amodiaquine, ally further comprise at least one API, wherein the antioxidant amodiaquine hydrochloride, amorolfine, amoxapine, amox and the API are independently adsorbed to a surface of at least icillin, amphecloral, amphetamine Sulfate, amphomycin, a portion of the polymeric particles and/or disposed in a pore amphotericin B, amplicillin, ampiroxicam, ampyZine Sulfate, of the porous network. amduinate, amrinone, aminone, amrubicin, amsacrine, 0050. Nonlimiting examples of APIs suitable for use in amythiamicin, anagestone acetate, anagrelide, anakinra. conjunction with the porous implants of the present invention ananain, anaritide, anaritide acetate, anastroZole (commer include, but are not limited to, 16-alpha fluoroestradiol, 16-al cially available as ARIMIDEXR from AstraZeneca), ana pha-gitoxin, 16-epiestriol, 17-alpha dihydroequilenin, 17-al Zolene Sodium, ancrod, andrographolide, androstenedione, pha estradiol, 17-beta estradiol, 17-hydroxy progesterone, angiogenesis inhibitors, angiotensin amide, anidoxime, 1-alpha-hydroxyvitamin D2, 1-dodecpyrrolidinone, 20-epi anileridine, anilopam hydrochloride, aniracetam, anirolac, 1.25 dihydroxyvitamin D3, 22-oxacalcitriol. 2CW. 2'-nor anisotropine methylbromide, anistreplase, anitraZafen, anor cGMP 3-isobutyl GABA, 5-ethynyluracil, 6-FUDCA, drin, antagonist D, antagonist G, antarelix, antazoline phos 7-methoxytacrine, abamectin, abanoquil, abcizimab (com phate, anthelmycin, anthralin, anthramycin, antiandrogen, mercially available as REOPROR) from Eli Lilly and Com antihemophilic factor (commercially available as XYN pany), abecarnil, abiraterone, ablukast, ablukast Sodium, THAR) from Pfizer, Inc.), acedapsone, felbamate, antiestro acadesine, acamprosate, acarbose, acebutolol, acecainide gen, antineoplaston, antipyrine, antisense oligonucleotides, hydrochloride, aceclidine, aceclofenae, acedapsone, ace apadoline, apafant, apalcillin Sodium, apaxifylline, apaZone, glutamide aluminum, acemannan, acetaminophen, aceta aphidicolin glycinate, apixifylline, apomorphine hydrochlo Zolamide, acetohexamide, acetohydroxamic acid, acetome ride, apraclonidine, apraclonidine hydrochloride, apramycin, pregenol, acetophenazine maleate, acetosulfone sodium, aprindine, aprindine hydrochloride, aprosulate Sodium, apro acetylcholine chloride, acetylcysteine, acetyl-L-carnitine, tinin, aptazapine maleate, aptiganel, apurinic acid, apurinic acetylmethadol, acifran, acipimoX, acitemate, acitretin, acivi acid, aranidipine, aranotin, arbaprostil, arbekicin, 1-methyl cin, aclarubicin, aclatonium, acodazole hydrochloride, aco 2-((phenylthio) methyl)-3-carbethoxy-4-(dimethylamino) niazide, acrisorcin, acrivastine, acronine, actisomide, actodi methyl)-5-hydroxy-6-bromindole (commercially available gin, acyclovir, acylfulvene, adafenoxate, adalimumab as ARBIDOL(R) from Masterlek), arbutamine hydrochloride, (commercially available as HUMIRAR) from Abbott Labora arclofenin, ardeparin sodium, (2R,4R)-1-(2S)-5-(diami tories), adapalene, adapalene, adatanserin, adatanserin nomethylideneamino) -2-((3R)-3-methyl-1,2,3,4-tetrahyd US 2014/0052264 A1 Feb. 20, 2014

roquinolin-8-yl Sulfonylamino pentanoyl-4-methyl-pip monidine, brinolase, brocresine, brocrinat, brofoxine, broma eridine-2-carboxylic acid (commercially available as doline maleate, bromazepam, bromchlorenone, bromelains, ARGATROBANR) from GlaxoSmithKline), arginine, bromfenac, brominidione, bromocriptine, bromodiphenhy argipressin tannate, arildone, aripiprazol, arotinolol, arpi dramine hydrochloride, bromoxamide, bromperidol, bromp nocid, arteflene, artilide fumarate, asimadoline, aspalatone, eridol decanoate, brompheniramine baleate, broperamole, asparaginase, aspartic acid, aspartocin, asperfuran, aspirin, bropirimine, brotizolam, bucamide maleate, bucindolol. aspoxicillin, asprelin, astemizole, astromicin Sulfate, asula buclizine hydrochloride, bucromarone, budesonide (com crine, atameStane, atenolol, atevirdine, atipamezole, atiprosin mercially available as RHINOCORTR and ENTOCORTR maleate, atolide, atorvastatin (commercially available as from AstraZeneca), budipine, budotitane, buformin, bumet LIPITOR(R) from Pfizer, Inc.), atosiban, atovaquone, atpenin anide, bunaprolast, bunaZosin, bunolol hydrochloride, bupi B. atracurium besylate, atrimustine, atrinositol, atropine, comide, bupivacaine hydrochloride, buprenorphine hydro auranofin, aureobasidin A, aurothioglucose, avilamycin, chloride, bupropion hydrochloride, buramate, buserelin avoparcin, avridine, nizatidine (commercially available as acetate, buspirone hydrochloride, busulfan, butabarbital, AXID(R) from GlaxoSmithKline), axinastatin 1, axinastatin2, butacetin, butaclamol hydrochloride, butalbital, butamben, axinastatin 3, azabon, azacitidinie, azaclorzine hydrochlo butamirate citrate, butaperazine, butaprost, butedronate tetra ride, azaconazole, azadirachtine, azalanstat dihydrochloride, Sodium, butenafine, buterizine, buthionine Sulfoximine, azaloxan fumarate, azanator maleate, azanidazole, azaper butikacin, butilfenin, butirosin sulfate, butixirate, butixocort one, azaribine, azaserine, aZasetron, azatadine maleate, aza propionate, butoconazole nitrate, butonate, butopamine, thioprine, azathioprine sodium, azatoxin, azatyrosine, azelaic butoprozine hydrochloride, butorphanol, butoxamine hydro acid, azelastine, azelnidipine, azepindole, azetepa, azimilide, chloride, butriptyline hydrochloride, cactinomycin, cadex azithromycin, azlocillin, azolimine, aZosemide, azotomycin, omer iodine, caffeine, calanolide A, calcifediol, calcipot aztreonam, aZumolene Sodium, bacampicillin hydrochloride, riene, calcipotriol, calcitonin, calcitriol, calcium baccatin III, bacitracin, baclofen, bacoside A, bacoside B, undecylenate, callphostin C, calusterone, cambendazole, bactobolamine, balanol, balaZipone, balhimycin, balofloxa camonagrel, camptothecin derivatives, canarypox IL-2, can cin, balsalazide, bambermycins, bambuterol, bamethan Sul desartan, candicidin, candoXatril, candoxatrilat, caniglibose, fate, bamifylline hydrochloride, bamidazole, baohuoside 1, canrenoate potassium, canrenone, capecitabine, capobenate barmastine, barnidipine, basifungin, batanopride hydrochlo Sodium, capobenic acid, capreomycin Sulfate, capromab, ride, batebulast, batelapine maleate, batimastat, beauvericin, capsaicin, captopril, capuride, caracemide, carbachol, carba becanthone hydrochloride, becaplermin, becliconazole, dox, carbamazepine, carbamide peroxide, carbantel lauryl beclomethasone dipropionate, befloxatone, beinserazide, Sulfate, carbaspirin calcium, carbazeran, carbazomycin C, belfosdil, belladonna, beloxamide, bemesetron, bemitradine, carbenicillin potassium, carbenoXolone sodium, carbetimer, bemoradan, benapryzine hydrochloride, benazepril hydro carbetocin, carbidopa, carbidopa-levodopa, carbinoxamine chloride, benazeprilat, bendacalol mesylate, bendazac, ben maleate, carbiphene hydrochloride, carbocloral, carbocys droflumethiazide, benflumetol, benidipine, benorterone, teine, carbol-fuchsin, carboplatin, carboprost, carbovir, car benoxaprofen, benoxaprofen, benoximate hydrochloride, boxamide-amino-triazole, carboxyamidotriazole, carboxym benperidol, bentazepam, bentiromide, benurestat, benzbro ethylated beta-1,3-glucan, carbuterol hydrochloride, CaRest marone, benzethonium chloride, benzetimide hydrochloride, M3, carfentanil citrate, carisoprodol, carmantadine, carmus benzilonium bromide, benzindopyrine hydrochloride, ben tine, CARN 700, camidazole, caroxazone, carperitide, car Zisoxazole, benzocaine, benzochlorins, benzoctamine hydro phenazine maleate, carprofen, carsatirin Succinate, carta chloride, benzodepa, benzoidaZOXan, benzonatate, benzoyl Zolate, carteolol, carteolol hydrochloride, cartilage derived peroxide, benzoylpas calcium, benzoylstaurosporine, ben inhibitor, carubicin hydrochloride, carumonam Sodium, Zquinamide, benzthiazide, benztropine, benztropine mesy carvedilol, carvotroline, carvotroline hydrochloride, carze late, benzydamine hydrochloride, benzylpenicilloyl polyl lesin, casein kinase inhibitors (ICOS), castanospermine, cau ysine, bepridil, bepridil hydrochloride, beractant, beraprost, rumonam, cebaracetam, cecropin B, cedefingol, cefaclor, berefrine, berlafenone, bertosamil, berythromycin, besipird cefadroxil, cefamandole, cefaparole, cefatrizine, cefazaflur ine, beta-alethine, betaclamycin B, betamethasone, betami Sodium, cefazolin, cefbuperaZone, cefcapene pivoxil, cefdal pron, betaxolol, betaxolol hydrochloride, bethanechol chlo oxime pentexil tosilate, cefdinir, cefditoren pivoxil, ride, bethanidine sulfate, betulinic acid, bevacizumab cefepime, cefetamet, cefetecol, cefixime, cefluprenam, (commercially available as AVASTINR) available from cefinenoXime hydrochloride, cefinetazole, cefiminlox, cefo Genenetech), bevantolol, bevantolol hydrochloride, bezafi dizime, cefonicid sodium, cefoperaZone sodium, ceforanide, brate, bFGF inhibitor, bialamicol hydrochloride, biapenem, cefoselis, cefotaxime Sodium, cefotetan, cefotiam, cefoxitin, bicalutamide, bicifadine hydrochloride, biclodil hydrochlo cefoZopran, cefpimizole, cefpiramide, cefpirome, cefpo ride, bidisomide, bifemelane, bifonazole, bimakalim, doXime proxetil, cefprozil, cefroxadine, cefsulodin, ceftazi bimithil, bindarit, biniramycin, binospirone, bioxalomycin dime, cefteram, ceftibuten, ceftizoxime Sodium, ceftriaxone, alpha2, bipenamol hydrochloride, biperiden, biphenamine cefuroxime, celastrol, celikalim, celiprolol, cepacidine A, hydrochloride, biriperone, bisantrene, bisaramil, bisaziridi cephacetrile Sodium, cephalexin, cephaloglycin, cephalori nylspermine, bis-benzimidazole A, bis-benzimidazole B. dine, cephalothin Sodium, cephapirin Sodium, cephradine, bisnafide, bisobrin lactate, bisoprolol, bispyrithione mag cericlamine, cerivastatin, ceronapril, certoparin Sodium, sulfex, bistramide D, bistramide K, bistratene A, bithionolate ceruletide, cetaben Sodium, cetalkonium chloride, cetamolol sodium, bitolterol besylate, bivalirudin, bizelesin, bleomycin hydrochloride, cetiedil, cetirizine, cetophenicol, cetraxate sulfate, bolandiol dipropionate, bolasterone, boldenone hydrochloride, cetrorelix, cetuximab (commercially avail undecylenate, boldine, bolenol, bolmantalate, bopindolol. able as ERBITUXOR) from Eli Lilly and Company), cetylpy bosentan, boxidine, brefeldin, breflate, brequinar sodium, ridinium chloride, chenodiol, chlophedianol hydrochloride, bretazenil, bretylium bosylate, brifentanil hydrochloride, bri chloral betaine, chlorambucil, chloramphenicol, chlordan US 2014/0052264 A1 Feb. 20, 2014 toin, chlordiazepoxide, chlorhexidine gluconate, chlorins, cyclosporine, cyclothialidine, cyclothiazide, cyclothiazomy chlormadinone acetate, chloroorienticin A, chloroprocaine cin, cyheptamide, cypemycin, cypenamine hydrochloride, hydrochloride, chloropropamide, chloroquine, chloroqui cyprazepam, cyproheptadine hydrochloride, cyprolidol noxaline Sulfonamide, chlorothiazide, chlorotrianisene, hydrochloride, cyproterone, cyproximide, cysteamine, cys chloroxine, chloroxylenol, chlorphenesin carbamate, chlor teine hydrochloride, cystine, cytarabine, cytarabine hydro pheniramine maleate, chlorpromazine, chlorpropamide, chloride, cytarabine ocfosfate, cytochalasin B, cytolytic fac chlorprothixene, chlortetracycline bisulfate, chlorthalidone, tor, cytostatin, dacarbazine, dacliximab, dactimicin, chlorZoxazone, cholestyramine resin, chromonar hydrochlo dactinomycin, daidzein, daledalin tosylate, dalfopristin, ride, cibenzoline, cicaprost, ciclafrine hydrochloride, dalteparin Sodium, daltroban, dalvastatin, danaparoid, dana ciclazindol, ciclesonide, cicletanine, ciclopiroX, cicloprofen, Zol, dantrolene, daphlnodorin A, dapiprazole, dapitant, cicloprolol, cidofovir, cidoxepin hydrochloride, cifenline, dapoxetine hydrochloride, dapsone, daptomycin, dargilita ciglitaZone, ciladopa hydrochloride, cilansetron, cilastatin Zone sodium, darifenacin, darlucin A, darodipine, darsidom Sodium, cilaZapril, cilnidipine, cilobamine mesylate, cilobra ine, darusentan, daunorubicin hydrochloride, daZadrol male dine, cillofungin, cilostazol, cimaterol, cimetidine, ate, dazepinil hydrochloride, daZmegrel, dazopride fumarate, cimetropium bromide, cinalukast, cinanserin hydrochloride, dazoxiben hydrochloride, debrisoquin sulfate, decitabine, cinepazet maleate, cinflumide, cingestol, cinitapride, cin deferiprone, deflazacort, dehydrocholic acid, dehydrodidem namedrine, cinnarizine, cinolazepam, cinoxacin, cinperene, nin B, dehydroepiandrosterone, delapril, delapril hydrochlo cinromide, cintaZone, cintriamide, cioteronel, cipamfylline, ride, delavirdine mesylate, deleguamine, delfaprazine, del ciprefadol Succinate, ciprocinonide, ciprofibrate, ciprofloxa madinone acetate, delmopinol, delphinidin, demecarium cin, ciprostene, ciramadol, cirolemycin, cisapride, cisatracu bromide, demeclocycline, demecycline, demoxepam, deno rium besilate, cisconazole, cisplatin, cis-porphyrin, cistineX fungin, deoxypyridinoline, 2-propylpentanoic acid (commer ine, citalopram, citenamide, citicoline, citreamicin alpha, cially available as DEPAKOTE(R) from Abbott), deprodone, cladribine, clamoxyquin hydrochloride, clarithromycin, deprostil, depsidomycin, deramciclane, dermatan Sulfate, clausenamide, clavulanate potassium, claZolam, claZolimine, desciclovir, descinolone acetonide, desflurane, desipramine clebopride, clemastine, Clentiazem maleate, clidinium bro hydrochloride, desirudin, deslanoside, deslorelin, desmo mide, clinafloxacin, clindamycin, clioquinol, clioxamide, pressin, desogestrel, desonide, desoximetasone, desoxoami cliprofen, clobazam, clobetasol propionate, clobetaSone odarone, desoxycorticosterone acetate, detajmium bitartrate, butyrate, clocortolone acetate, clodanolene, clodazon hydro deterenol hydrochloride, detirelix acetate, devazepide, dex chloride, clodronic acid, clof azimine, clofibrate, clofilium amethasone, dexamisole, dexbrompheniramine maleate, phosphate, clogestone acetate, clomacran phosphate, clom dexchlorpheniramine maleate, dexclamol hydrochloride, egestone acetate, clometherone, clomethiazole, clomifene dexetimide, dexfenfluramine hydrochloride, dexifosfamide, analogues, clominorex, clomiphene, clomipramine hydro deximafen, dexivacaine, dexketoprofen, dexloxiglumide, chloride, clonazepam, clonidine, clonitrate, clonixeril, dexmedetomidine, dexormaplatin, dexoxadrol hydrochlo clonixin, clopamide, clopenthixol, cloperidone hydrochlo ride, dexpanthenol, dexpemedolac, dexpropranolol hydro ride, clopidogrel (commercially available as PLAVIX(R) from chloride, dexraZoxane, dexSotalol, dextrin 2-sulphate, dex Bristol-Myers Squibb and Sanofi Pharmaceuticals), clopi troamphetamine, dextromethorphan, dextrorphan mozide, clopipazan mesylate, clopirac, cloprednol, clopros hydrochloride, dextrothyroxine Sodium, dexVerapamil, deza tenol sodium, cloraZepate dipotassium, clorethate, clorex guanine, dezinamide, dezocine, diacetolol hydrochloride, olone, cloroperone hydrochloride, clorprenaline diamocaine cyclamate, diapamide, diatrizoate meglumine, hydrochloride, clorsulon, clortermine hydrochloride, closan diatrizoic acid, diaveridine, diazepam, diaziquone, diaZOX tel, closiramine aceturate, clothiapine, clothixamide maleate ide, dibenzepin hydrochloride, dibenzothiophene, dibucaine, cloticaSone propionate, clotrimazole, cloxacillin benzathine, dichliorvos, dichloralphenaZone, dichlorphenamide, dicir cloxyquin, clozapine, cocaine, coccidioidin, codeine, enone, diclofenac sodium, dicloxacillin, dicranin, dicumarol, codoxime, colchicine, colestimide, colestipol hydrochloride, dicyclomine hydrochloride, didanosine, didemnin B, didox, colestolone, colforsin, colfosceril palmitate, colistimethate dienestrol, dienogest, diethylcarbamazine citrate, diethylho Sodium, colistin Sulfate, collismycin A, collismycin B, col mospermine, diethylnorspermine, diethylpropion hydrochlo terol mesylate, combretastatin A4, combretastatin analogue, complestatin, conagenin, conorphone hydrochloride, conti ride, diethylstilbestrol, difenoximide hydrochloride, difenoxin, diflorasone diacetate, difloxacin hydrochloride, gnasterol, contortrostatin, cormethasone acetate, corticorelin difluanine hydrochloride, diflucortolone, diflumidone ovine triflutate, corticotropin, cortisone acetate, cortivaZol. Sodium, diflunisal, difluprednate, diftalone, digitalis, digi cortodoxone, cosalane, costatolide, cosyntropin, cotinine, toxin, digoxin, dihexyverine hydrochloride, dihydrexidine, warfarin (commercially available as COUMADINR) from dihydro-5-azacytidine, dihydrocodeine bitartrate, dihydroer Bristol-Myers Squibb), coumermycin, crambescidin 816, gotamine mesylate, hihydroestosterone, dihydrostreptomy crilvastatin, crisinatol, cromitrile Sodium, cromolyn Sodium, cin Sulfate, dihydrotachysterol, dihydrotaxol, phenytoin crotamiton, cryptophycin 8, cucumariosid, cuprimyxin, cura (commercially available as DILANTINR) from Parke, Davis cin A, curdlan Sulfate, Zinc hyaluran (commercially available & Company), dilevalol hydrochloride, diltiazem hydrochlo as CURIOSINR) from Gedeon ride, dimefadane, dimefline hydrochloride, dimenhydrinate, 0052 Richter), cyclacillin, cyclazocine, cyclazosin, cyclic dimercaprol, dimethadione, dimethindene maleate, dimethis HPMPC, cyclindole, cycliramine maleate, cyclizine, terone, dimethyl prostaglandin A1, dimethyl Sulfoxide, dim cyclobendazole, cyclobenzaprine, cyclobut A, cyclobut G, ethylhomospermine, dimiracetam, dimoxamine hydrochlo cyclocapron, cycloguanil pamoate, cycloheximide, cyclo ride, dinoprost, dinoprostone, dioxadrol hydrochloride, pentanthraquinones, cyclopenthiazide, cyclopentolate dioxamycin, diphenhydramine citrate, diphenidol, diphe hydrochloride, cyclophenazine hydrochloride, cyclophos noxylate hydrochloride, diphenyl spiromustine, diplivefin phamide, cycloplatam, cyclopropane, cycloserine, cyclosin, hydrochloride, diplivefrin, dipliencyprone, diprafenone, US 2014/0052264 A1 Feb. 20, 2014

dipropylnorspermine, dipyridamole, dipyrithione, dipyrone, fenobam, fenoctimine sulfate, fenofibrate, fenoldopam, feno dirithromycin, discodermolide, disobutamide, disofenin, dis profen, fenoterol, fenpipalone, fenprinast hydrochloride, fen opyramide, disoxaril, disulfuram, ditekiren, divalproex prostalene, fenguizone, fenretinide, fenspiride, fentanyl cit Sodium, dizocilpine maleate, dobutamine, docarpamine, rate, fentiazac, fenticlor, fenticonazole, fenyripol docebenone, docetaxel, doconazole, docosanol, dolfetilide, hydrochloride, fepradinol, ferpifosate sodium, ferristene, fer dolasetron, drotrecogin alfa (commercially available as rixan, ferrous Sulfate, ferumoxides, ferumoxsil, fetoxylate XIGRIS(R) from Eli Lilly and Company), dulloxetine hydro hydrochloride, fexofenadine, fezolamine fumarate, fiacitab chloride (commercially available as CYMBALTAR) from Eli ine, fialuridine, fibrinogen I 125, filgrastim, filipin, finasteride Lilly and Company), ebastine, ebiratide, ebrotidine, ebselen, (commercially available as PROPECIAR) from Merck), fla ecabapide, ecabet, ecadotril, ecdlisteron, echicetin, echistatin, vodilol maleate, flavopiridol, flavoxate hydrochloride, flaza echothiophate iodide, eclanamine maleate, eclaZolast, eco lone, flecainide, flerobuterol, fleroxacin, flesinoxan, flestolol mustine, econazole, ecteinascidin 722, edaravone, edatrex sulfate, fletazepam, flezelastine, flobufen, floctafenine, flo ate, edelfosine, edifolone acetate, edobacomab, edoxudine, moxef, flordipine, florfenicol, florifenine, flosatidil, flose edrecolomab, edrophonium chloride, edroxyprogesteone quinan, floxacillin, floXuridine, fluasterone, fluazacort, fluba acetate, efegatran, eflornithine, efonidipine, egualcen, elant nilate hydrochloride, flubendazole, flucindole, flucloronide, rine, eleatonin, elemene, eletriptan, elgodipine, eliprodil, fluconazole, flucytosine, fludalanine, fludarabine phosphate, elsamitrucin, eltenae, elucaine, emalkalim, emedastine, fludazonium chloride, fludeoxyglucose F 18, fludorex, emetine hydrochloride, emiglitate, emilium tosylate, emite fludrocortisone acetate, flufenamic acid, flufenisal, flumaze fur, emoctakin, enadoline hydrochloride, enalapril, enalapri nil, flumecinol, flumequine, flumeridone, flumethasone, flu lat, enalkiren, enaZadrem, encyprate, endralazine mesylate, metramide, flumeZapine, fluminorex, flumizole, flumox endrysone, enflurane, englitaZone, enilconazole, enisoprost, onide, flunarizine, flunidazole, flunisolide, flunitrazepam, enlimomab, enloplatin, enofelast, enolicam sodium, enoxa flunixin, fluocalcitriol, fluocinolone acetonide, fluocinonide, cin, enoxacin, enoxaparin Sodium, enoxaparin Sodium, fluocortin butyl, fluocortolone, fluorescein, fluorodaunoruni enoXimone, enpiroline phosphate, enprofylline, empromate, cin hydrochloride, fluorodopa F 18, fluoroformylone, fluoro entacapone, enterostatin, enviradene, enviroXime, ephedrine, quinolones, fluorometholone, fluorouracil, fluotracen hydro epicillin, epimestrol, epinephrine, epinephrylborate, epipro chloride, fluoxetine, fluoxymesterone, fluparoxan, pidine, epirizole, epirubicin, epitetracycline hydrochloride, fluperamide, fluperolone acetate, fluphenazine decanoate, epithiazide, epoetinalfa, epoetin beta, epoprostenol, epopros flupirtine, fluprednisolone, fluproduaZone, fluprostenol tenol sodium, epoxymexrenone, epristeride, eprosartan, sodium, flucuaZone, fluradoline hydrochloride, flurandreno eptastigmine, equilenin, equilin, erbuloZole, erdosteine, lide, flurazepam hydrochloride, flurbiprofen, fluretofen, flu ergoloid mesylates, ergonovine maleate, ergotamine tartrate, rithromycin, fluorocitabine, fluorof amide, fluorogestone ersentilide, ersofermin, erythritol, erythrity1 tetranitrate, acetate, flurothyl, fluoroxene, fluspiperone, fluspirilene, flu erythromycin, esmolol hydrochloride, esomeprazole (com ticasone propionate (commercially available as ADVAIRR mercially available as NEXIUM(R) from AstraZeneca), eso from GlaxoSmithKline), fluticasone furoate, flutrimazole, rubicin hydrochloride, esproquin hydrochloride, estazolam, flutroline, fluvastatin, fluvastatin sodium, fluvoxamine, fluzi estradiol, estramustine, estramustine analogue, estraZinol namide, folic acid, follicle regulatory protein, folliculostatin, hydrobromide, estriol, estrofurate, estrogen agonists, estro fomepizole, fonazine mesylate, forasartan, forfenimex, for gen antagonists, estrogens, conjugated estrogens, esterified, fenirmex, formestane, formocortal, formoterol, fosarilate, estrone, estropipate, esuprone, etafedrine hydrochloride, fosazepam, foscarnet Sodium, fosfomycin, foSfonet Sodium, etanidazole, etanterol, etarotene, etazolate hydrochloride, fosinopril, fosinoprilat, fosphenyloin, fosquidone, fostedil, eterobarb, ethacizin, ethacrynate Sodium, ethacrynic acid, fostriecin, fotemustine, fuchsin, basic, fumoxicillin, fungi ethambutol hydrochloride, ethamivan, ethanolamine oleate, mycin, furaprofen, furazolidone, furazolium chloride, fure ethehlorvynol, ether, ethinyl estradiol, ethiodized oil, grelate Sodium, furobufen, furodazole, furosemide, fusidate ethionamide, ethonam nitrate, ethopropazine hydrochloride, Sodium, fusidic acid, gabapentin, gadobenate dimeglumine, ethosuximide, ethotoin, ethoxazene hydrochloride, ethyben gadobenic acid, gadobutrol, gadodiamide, gadolinium texa Ztropine, ethyl chloride, ethyl dibunate, ethylestrenol, ethyn phyrin, gadopentetate dimeglumine, gadoteric acid, gadoteri diol, ethynerone, ethynodiol diacetate, etibendazole, eti dol, gadoversetamide, galantamine, galdansetron, docaine, etidronate disodium, etidronic acid, etifenin, galdansetron hydrochloride, gallamine triethiodide, gallium etintidine hydrochloride, etizolam, etodolac, etofenamate, nitrate, gallopamil, galocitabine, gamfexine, gamolenic acid, etoformin hydrochloride, etomidate, etonogestrel, etoperi ganciclovir, ganirelix, ganirelix acetate, gelatinase inhibitors, done hydrochloride, etoposide, etoprine, etoxadrol hydro gemcadiol, gemcitabine (commercially available as chloride, etoZolin, etrabamine, etretinate, etryptamine GEMZARR) from Eli Lilly and Company), gemeprost, gem acetate, eucatropine hydrochloride, eugenol, euprocin hydro fibrozil, gentamicin Sulfate, gentian violet, gepirone, gesta chloride, eveminomicin, exametazine, examorelin, exaprolol clone, gestodene, gestonorone caproate, gestrinone, geVotro hydrochloride, exemestane, exetimibe (commercially avail line hydrochloride, girisopam, glaspimod, glaucocalyxin A, able as ZETIAR) from Merck), fadrozole, faerieflungin, fam glemanserin, gliamilide, glibornuride, glicetanile Sodium, ciclovir, famotidine (commercially available as PEPCIDR) gliflumide, glimepiride, glipizide, gloximonam, glucagon, from Merck), fampiridine, fantofarone, fantridone hydrochlo glutapyrone, glutathione inhibitors, glutethimide, glyburide, ride, faropenem, fasidotril, fasudil, faZarabine, fedotozine, glycopine, glycopril, glycopyrrolate, glyhexamide, glymi felbamate, felbinac, felodipine, fely pressin, femalamide, fen dine sodium, glyoctamide, glyparamide, colloidal gold Au amole, fenbendazole, fenbufen, fencibutirol, fenclofenac, 198, gonadoctrinins, gonadorelin, gonadotropins, goserelin, fenclonine, fenclorac, fendosal, fenestrel, fenethylline hydro gramicidin, granisetron, grepafloxacin, griseofulvin, guaiap chloride, fenfluramine hydrochloride, fengabine, fenimide, ate, guaithylline, guanabenZ, guanabenz acetate, guanadrel fenisorex, fenmetozole hydrochloride, fenmetramide, Sulfate, guancydine, guanethidine monosulfate, guanfacine US 2014/0052264 A1 Feb. 20, 2014 hydrochloride, guanisoquin Sulfate, guanoclor Sulfate, gua isepamicin, isobengaZole, isobutamben, isocarboxazid, iso noctine hydrochloride, guanoxabenZ, guanoxan Sulfate, gua conazole, isoetharine, isofloxythepin, isoflupredone acetate, noxyfen Sulfate, gusperimus trihydrochloride, halazepam, isoflurane, isofluorophate, isohomohalicondrin B, isoleucine, halcinonide, halichondrin B, halobetasol propionate, halof isomazole hydrochloride, isomylamine hydrochloride, iso antrine, halofantrine hydrochloride, halofenate, halofugi niazid, isopropamide iodide, isopropyl alcohol, isopropyl none hydrobromide, halomon, galopemide, galoperidol. unoprostone, isoproterenolhydrochloride, isosorbide, isosor halopredone, haloprogesterone, haloprogin, halothane, bide mononitrate, isotiquimide, isotretinoin, isoxepac, isoxi halquinols, hamycin, han menopausal gonadotropins, cam, isoxSuprine hydrochloride, isradipine, itameline, hatomamicin, hatomarubigin A, hatomarubigin B, hatomaru itasetron, itaZigrel, itopride, itraconazole, ivermectin, jas bigin C, hatomarubigin D, heparin Sodium, hepsulfam, plakinolide, josamycin, kahalalide F. kalafungin, kanamycin heregulin, hetacillin, heteronium bromide, hexachlorophene: Sulfate, ketamine hydrochloride, ketanserin, ketazocine, hydrogen peroxide, hexafluorenium bromide, hexamethylene ketazolam, kethoxal, ketipramine fumarate, ketoconazole, bisacetamide, hexedine, hexobendine, hexoprenaline Sulfate, ketoprofen, ketorfanol, ketorolac, ketotifen fumarate, kitasa hexylresorcinol, histamine phosphate, histidine, histoplas mycin, labetalol hydrochloride, lacidipine, lacidipine, lacti min, histrelin, homatropine hydrobromide, hoquizil hydro tol, lactivicin, laennec, lafutidine, lamellarin-n triacetate, chloride, human chorionic gonadotropin, hycanthone, lamifiban, lamivudine, lamotrigine, lanoconazole, LAN hydralazine hydrochloride, hydralazine polistirex, hydro OXINR) (digoxin, available from GlaxoSmithKline), lan chlorothiazide, hydrocodone bitartrate, hydrocortisone, perisone, lanreotide, lanSoprazole (commercially available as hydroflumethiazide, hydromorphone hydrochloride, PREVAID(R) from Takeda Pharmaceuticals, Inc.), latano hydroxyamphetamine hydrobromide, hydroxychloroquine prost, lateritin, laurocapram, lauryl isoquinolinium bromide, Sulfate, hydroxyphenamate, hydroxyprogesterone caproate, lavoltidine Succinate, lazabemide, lecimibide, leinamycin, hydroxyurca, hydroxy Zine hydrochloride, hymecromone, lemildipine, leminoprazole, lenercept, leniquinsin, hyoscyamine, hypericin, ibafloxacin, ibandronic acid, lenograstim, lenperone, lentinan Sulfate, leptin, leptolstatin, ibogaine, ibopamine, ibudilast, ibufenac, ibuprofen, ibutilide lercanidipine, lergotrile, lerisetron, letimide hydrochloride, fumarate, icatibant acetate, ichthammol, icotidine, idarubi letraZuril, letrozole, leucine, leucomyzin, leuprolide acetate, cin, idoxifene, idoxuridine, idramantone, iemefloxacin, ieso leuprolide, leuprorelin, levamfetamine Succinate, levamisole, pitron, ifetroban, ifosfamide, ilepeimide, illimaquinone, levdobutamine lactobionate, levcromakalim, levetiracetam, ilmofosine, illomastat, illonidap, illoperidone, iloprost, imafen levobetaxolol, levobunolol, levobupivacaine, levocabastine, hydrochloride, imazodan hydrochloride, imidapril, imidaze levocarnitine, levodopa, levodropropizine, levofloxacin nil, imidazoacridones, imidecyl iodine, imidocarb hydro (commercially available as LEVAQUINR) from Jessen Phar chloride, imidoline hydrochloride, imidurea, imiloxanhydro maceuticals, Inc.), levofuraltadone, levoleucovorin calcium, chloride, imipenem, imipramine hydrochloride, imiquimod, levomethadyl acetate, levomethadyl acetate hydrochloride, immunostimulant peptides, impromidine hydrochloride, levomoprolol, levonantradol hydrochloride, levonordefrin, indacrinone, indapamide, indecainide hydrochloride, indel levonorgestrel, levopropoxyphene napsylate, levopropylcil oxazine hydrochloride, indigotindisulfonate sodium, indi lin potassium, levormeloxifene, levorphanol tartrate, levosi navir, indocyanine green, indolapril hydrochloride, indol mendan, levoSulpiride, levothyroxine sodium, levoxadrol idan, indometacin, indomethacin Sodium, indoprofen, hydrochloride, lexipa?ant, lexithromycin, liarozole, libenza indoramin, indorenate hydrochloride, indoxole, indriline pril, lidamidine hydrochloride, lidocaine, lidofenin, lidofla hydrochloride, infliximab (commercially available as REMI zine, lifarizine, lifibrate, lifibrol, linarotene, lincomycin, lin CADE(R) from Janssen Biotech, Inc.), inocoterone, inogatran, ear polyamine analogue, linogliride, linopirdine, linotroban, inolimomab, inositol niacinate, insulin, insulin glargine linsidomine, lintitript, lintopride, liothyronine I 125, liothy (commercially available as LANTUS(R) from Sanofi-Aven ronine Sodium, liotrix, lirexapride, lisinopril, lissoclinamide tis), interferons, interferon beta-1a (commercially available 7, lixazinone sulfate, lobaplatin, lobenzarit sodium, lobu as AVONEX(R) from BIOGEN), interleukins, intrazole, cavir, lodelaben, lodoxamide, lofemizole hydrochloride, intriptyline hydrochloride, iobenguane, iobenzamic acid, lofentanil oxalate, lofepramine hydrochloride, lofexidine iobitridol, iocarmate meglumine, iocarmic acid, iocetamic hydrochloride, lombricine, lomefloxacin, lomerizine, lom acid, iodamide, iodine, iodipamide meglumine, iodixanol, etraline hydrochloride, lometrexol, lomitapide, lomofungin, iodoamiloride, iodoantipyrine I 131, iodocholesterol I 131, lornoxicam, lomustine, lonapalene, lonazolac, lonidamine, iododoxorubicin, iodohippurate sodium I 131, iodopyracet I loperamide hydrochloride, loracarbef, lorajmine hydrochlo 125, iodoquinol, iodoxamate meglumine, iodoxamie acid, ride, loratadine, lorazepam, lorbamate, lorcainide hydrochlo ioglicic acid, iofetamine hydrochloride I 123, iofratol, ioglu ride, lorecleZole, lorglumide, lormetazepam, lornoxicam, lor col, ioglucomide, ioglycamic acid, iogulamide, iohexyl, noxicam, lortalamine, lorZafone, losartan (commercially iomeprol, iomethin I 125, iopamidol, iopanoic acid, iopentol, available as COZAAR(R) from Merck), losigamone, losox iophendylate, ioprocemic acid, iopromide, iopronic acid, antrone, losulazine hydrochloride, loteprednol, lovastatin, iopydol, iopydone, iopyrol, iosefamic acid, ioseric acid, ioSu loviride, loxapine, loxoribine, lubeluzole, lucanthone hydro lamide meglumine, ioSumetic acid, iotasul, iotetric acid, chloride, lufironil, lurosetron mesylate, lurtotecan, luteiniz iothalamate sodium, iothalamic acid, iotriside, iotrolan, ing hormone, lutetium, lutrelin acetate, luzindole, lyapolate iotroXic acid, iotyrosine I 131, ioversol, ioxagiate Sodium, Sodium, lycetamine, lydicamycin, lydimycin, lynestrenol, ioxaglate meglumine, ioxaglic acid, iOXilan, ioxotrizoic acid, lypressin, lysine, lysofylline, lysostaphin, lytic peptides, ipazilide, ipenoxazone, ipidacrine, ipodate calcium, maduramicin, mafenide, magainin 2 amide, magnesium sali ipomeanol, 4-, ipratropium bromide, ipriflavone, iprindole, cylate, magnesium sulfate, magnolol, maitansine, male iprofenin, ipronidazole, iproplatin, iproxamine hydrochlo thamer, mallotochromene, mallotojaponin, malotilate, man ride, ipsapirone, irbesartan, irinotecan, irloxacin, iroplact, gafodipir, manidipine, maniwamycin A, mannitol, irsogladine, irtemazole, isalsteine, isamoXole, isbogrel, mannostatin A, manumycin E, manumycin F, MAPK/ERK US 2014/0052264 A1 Feb. 20, 2014

kinase (MEK) inhibitors, mapinastine, maprotiline, marim ate, monensin, monoctanoin, montelukast sodium (commer astat, masoprocol, maspin, massetolide, matrilysin inhibitors, cially available as SINGULAIRR) available from Merck), maytansine, mazapertine Succiniate, mazindol, mebenda montirelin, mopidamol, moracizine, morantel tartrate, mori Zole, mebeverine hydrochloride, mebrofenin, mebutamate, cizine, morniflumate, morphine, morphine Sulfate, morrhuate mecamylamine hydrochloride, mechlorethamine hydrochlo Sodium, mosapramine, mosapride, motilide, motretinide, ride, meclocycline, meclofenamate Sodium, mecloqualone, moxalactam disodium, moxazocine, moxiraprine, moxnida meclorisone dibutyrate, medazepam hydrochloride, Zole, moXonidine, mumps skin testantigen, mustard antican medorinone, medrogestone, medroxalol, medroxyprogester cer agent, muZolimine, mycaperoxide B, mycophenolic acid, one (commercially available as DEPO-PROVERAR) from myriaporone, nabazenil, nabilone, nabitan hydrochloride, Pfizer, Inc.), medrysone, meelizine hydrochloride, mefe naboctate hydrochloride, nabumetone, n-acetyldinaline, namic acid, mefenidil, mefenorex hydrochloride, mefexam nadide, nadifloxacin, nadolol, nadroparin calcium, nafadot ide, mefloquine hydrochloride, mefruside, megalomicin ride, nafamo.stat, nafarelin, nafcillin sodium, nafenopin, potassium phosphate, megestrol acetate, meglumine, meglu nafimidone hydrochloride, naflocort, nafomine malate, tol, melengestrol acetate, melitracen hydrochloride, mel nafoxidine hydrochloride, nafronyl oxalate, naftifine hydro phalan, memotine hydrochloride, menabitan hydrochloride, chloride, naftopidil, naglivan, nagreStip, nalbuphine hydro menoctone, menogaril, menotropins, meobentine Sulfate, chloride, nalidixate Sodium, nalidixic acid, nalmefene, mepartricin, mepenZolate bromide, meperidine hydrochlo nalmexone hydrochloride, naloxone/pentazocine, naltrex ride, mephentermine Sulfate, mephenyloin, mephobarbital, one, namoxyrate, nandrolone phenpropionate, nantradol mepivacaine hydrochloride, meprobamate, meptazinol hydrochloride, napactadine hydrochloride, napadisilate, hydrochloride, medulidox, meralein sodium, merbarone, mer napamezole hydrochloride, napavin, naphazoline hydro captopurine, mercufenol chloride, mercury, meropenem, chloride, naphterpin, naproxen, naproXol, napsagatran, nara mesalamine, meseclaZone, mesoridazine, mesterolone, nol hydrochloride, narasin, naratriptan, nartograstim, nasaru mestranol, meSuprine hydrochloride, metalol hydrochloride, plase, natamycin, nateplase, naxagolide hydrochloride, metaproterenol polistirex, metaraminol bitartrate, metaxa nebivolol, nebramycin, medaplatin, nedocromil, nefazodone lone, meteneprost, meterelin, metformin, methacholine chlo hydrochloride, neflumozide hydrochloride, nefopam hydro ride, methacycline, methadone hydrochloride, methadyl chloride, neleZaprine maleate, nemazoline hydrochloride, acetate, methalthiazide, methamphetamine hydrochloride, nemorubicin, neomycin palmitate, neostigmine bromide, methaqualone, methazolamide, methdilazine, methenamine, neridronic acid, netilmicin Sulfate, neutral endopeptidase, methenolone acetate, methetoin, methicillin sodium, methi neutramycin, nevirapine, nexeridine hydrochloride, niacin, mazole, methioninase, methionine, methisaZone, methixene nibroxane, nicardipine hydrochloride, nicergoline, niclosa hydrochloride, methocarbamol, methohexital sodium, mide, nicorandil, nicotinyl alcohol, nicotine (commercially methopholine, methotrexate, methotrimeprazine, meth available as NICOTROL(R) NS from Pfizer, Inc.), nifedipine, Oxatone, methoxyflurane, methSuximide, methyclothiazide, nifirmerone, nifluridide, nifuradene, nifuraldezone, nifuratel, methyl 10 palmoxirate, methylatropine nitrate, methylbenze nifuratrone, nifurdazil, nifurimide, nifurpirinol, thonium chloride, methyldopa, methyldopate hydrochloride, nifurquinazol, nifurthiazole, nilutamide, nilvadipine, nima methylene blue, methylergonovine maleate, methylhista Zone, nimodipine, niperotidine, niravoline, niridazole, nisa mine, R-alpha, methylinosine monophosphate, methylpheni mycin, nisbuterol mesylate, nisin, nisobamate, nisoldipine, date hydrochloride, methylprednisolone, methyltestosterone, nisoxetine, nisterime acetate, nitarSone, nitaZoxamide, nite methynodiol diacelate, methysergide, methysergide maleate, capone, nitrafudam hydrochloride, nitralamine hydrochlo metiamide, metiapine, metioprim, metipamide, metipra ride, nitramisole hydrochloride, nitrazepam, nitrendipine, nolol, metizoline hydrochloride, metkephamid acetate, meto nitrocycline, nitrodan, nitrofurantoin, nitrofuraZone, nitro clopramide, metocurine iodide, metogest, metolaZone, glycerin, nitromersol, nitromide, nitromifene citrate, nitrous metopimazine, metoprine, metoprolol, metoquizine, metri oxide, nitroxide antioxidant, nitrullyn, nivaZol. nivimedone fonate, metrizamide, metrizoate Sodium, metronidazole, Sodium, nizatidine, noberastine, nocodazole, nogalamycin, meturedepa, metyrapone, metyrosine, mexiletine hydrochlo nolinium bromide, nomifensine maleate, noracymethadol ride, mexrenoate potassium, meZlocillin, mfonelic acid, hydrochloride, norbolethone, norepinephrinebitartrate, nore mianserin hydrochloride, mibefradil, mibefradil dihydro thindrone, norethynodrel, norfloxacin, norflurane, norgesti chloride, mibolerone, michellamine B, miconazole, micro mate, norgestomet, norgestrel, nortriptyline hydrochloride, colin A, midaflur, midazolam hydrochloride, midodrine, noscapine, novobiocin Sodium, N-Substituted benzaimides, mifepristone, mifobate, miglitol, millacemide, milameline, nufenoXole, nylestriol, nystatin, O6-benzylguanine, obi mildronate, milemperone, millipertine, milnacipran, mil doXime chloride, ocaperidone, ocfentanil hydrochloride, oci rinone, miltefosine, mimbane hydrochloride, minaprine, naplon, octanoic acid, octaZamide, octenidine hydrochloride, minaxolone, minocromil, minocycline, minoxidil, miofla octodrine, octreotide, octriptyline phosphate, ofloxacin, Zine hydrochloride, miokamycin, mipragoside, mirfentanil, oformine, okicenone, olanzapine (commercially available as mirimoStim, mirincamycin hydrochloride, mirisetron male ZYPREXAR) from Eli Lilly and Company), oligonucle ate, mirtazapine, mismatched double stranded RNA, mis otides, olopatadine, olprinone, olsalazine, olsalazine Sodium, onidazole, misoprostol, mitindomide, mitocarcin, mitocro olvanil, omeprazole, onapristone, ondansetron, ontazolast, min, mitogillin, mitoguaZone, mitolactol, mitomalcin, oocyte maturation inhibitor, opipramol hydrochloride, ora mitomycin, mitonafide, mitosper, mitotane, mitoxantrone, cin, orconazole nitrate, orgotein, orlislat, ormaplatin, orme mivacurium chloride, mivaZerol, mixanpril, mixidine, mizo toprim, ornidazole, orpanoxin, orphenadrine citrate, osater lastine, mizoribine, moclobemide, modafinil, modaline Sul one, otenZepad, oxacillin Sodium, oxagrelate, Oxaliplatin, fate, modecamide, moexipril, mofarotene, mofegiline hydro oXamarin hydrochloride, oxamisole, oxamniquine, oxan chloride, mofeZolac, molgramoStim, molinaZone, molindone drolone, Oxantel pamoate, oxaprotiline hydrochloride, hydrochloride, molsidomine, mometasone, monatepil male oxaprozin, oxarbazole, Oxatomide, oxaunomycin, oxazepam, US 2014/0052264 A1 Feb. 20, 2014

oXcarbazepine, Oxendolone, oxethazaine, oxetorone fuma palmitate, pipoxolan hydrochloride, piprozolin, piquindone rate, Oxfendazole, Oxfenicine, Oxibendazole, oxiconazole, hydrochloride, piquizil hydrochloride, piracetam, piran oxidopamine, oxidronic acid, oxifungin hydrochloride, damine hydrochloride, pirarubicin, piraZmonam Sodium, oXilorphan, oximonam, oximonam sodium, OXiperomide, piraZolac, pirbenicillin Sodium, pirbuterol acetate, piremper oxiracetam, oxiramide, Oxisuran, oxmetidine hydrochloride, one, pirenzepine hydrochloride, piretanide, pirfenidone, piri oXodipine, oxogestone phenpropionate, oxolinic acid, Oxpre dicillin Sodium, piridironate sodium, piriprost, piritrexim, nolol hydrochloride, oxtriphylline, oxybutynin chloride, oxy pirlimycin hydrochloride, pirlindole, pirmagrel, pirmenol chlorosene, oxycodone, oxymetazoline hydrochloride, hydrochloride, pirnabine, piroctone, pirodavir, pirodomast, oxymetholone, oxymorphone hydrochloride, oxypertine, pirogliride tartrate, pirolate, pirolaZamide, piroxantrone oxyphenbutaZone, oxypurinol, oxytetracycline, oxytocin, hydrochloride, piroxicam, piroXimone, pirprofen, pirquino oZagrel, oZolinone, paclitaxel, palauamine, paldimycin, pali Zol, pirsidomine, prenylamine, pitavastatin (commercially navir, paliperidone (commercially available as INVEGAR) available as LIVALOAR) from from Janssen Pharmaceuticals, Inc.), paliperidone palmitate 0053 Eli Lilly and Company), pituitary, posterior, piv (commercially available as INVEGAR SUSTENNAR) from ampicillin hydrochloride, pivopril, pizotyline, placetin A, Janssen Pharmaceuticals, Inc.), palmitoylrhizoxin, palmox platinum compounds, platinum-triamine complex, plicamy irate Sodium, pamaqueside, pamatolol Sulfate, pamicogrel, cin, plomestane, pobilukast edamine, podofilox, poisonoak pamidronate disodium, pamidronic acid, panadiplon, pan extract, poldine methylsulfate, poliglusam, polignate Sodium, amesine, panaxytriol, pancopride, pancuronium bromide, polymyxin B sulfate, polythiazide, ponalrestat, porfimer panipenem, pannorin, panomifene, pantethine, pantoprazole, Sodium, porfiromycin, potassium chloride, potassium iodide, papaverine hydrochloride, parabactin, parachlorophenol, potassium permanganate, povidone-iodine, practolol, prali paraldehyde, paramethasone acetate, paranyline hydrochlo doXime chloride, pramiracetam hydrochloride, pramoxine ride, parapenzolate bromide, pararosaniline pamoate, par hydrochloride, pranolium chloride, prasugrel (commercially bendazole, parconazole hydrochloride, paregoric, pareptide available as EFFIENTR) from Eli Lilly and Company), pra Sulfate, pargyline hydrochloride, parnaparin Sodium, paro Vadoline maleate, pravastatin, prazepam, praZosin, praZosin momycin Sulfate, paroxetine (commercially available as hydrochloride, prednazate, prednicarbate, prednimustine, PAXILR) from GlaxoSmithKlein), parthenolide, partricin, prednisolone, prednisone, prednival, pregabalin (commer paulomycin, paZelliptine, paZinaclone, paZoxide, paZufloxa cially available as LYRICAR) from Pfizer, Inc.), preg cin, pefloxacin, pegaspargase, pegorgotein, pelanserin hydro nenolone Succiniate, prenalterol hydrochloride, pridefine chloride, peldesine, peliomycin, pelretin, pelrinone hydro hydrochloride, prifelone, prilocalne hydrochloride, prilosec, chloride, pemedolac, pemerid nitrate, pemetrexed, primaquine phosphate, primidolol, primidone, prinivil, pri pemirolast, pemoline, penamecillin, penbutolol sulfate, pen nomide tromethamine, prinoXodan, prizidilol hydrochloride, ciclovir, penfluridol, penicillin G benzathine, penicillin G proadifen hydrochloride, probenecid, probicromil calcium, potassium, penicillin G procaine, penicillin G Sodium, peni probucol, procainamide hydrochloride, procaine hydrochlo cillin V, penicillin V benzathine, penicillin V hydrabamine, ride, procarbazine hydrochloride, procaterol hydrochloride, penicillin V potassium, pentabamate, pentaerythritol tetrani prochlorperazine, procinonide, proclonol, procyclidine trate, pentafuside, pentamidine, pentamorphone, bentamus hydrochloride, prodilidine hydrochloride, prodolic acid, prof tine, pentapiperium methylsulfate, pentazocine, pentetic adol hydrochloride, progabide, progesterone, proglumide, acid, pentiapine maleate, pentigetide, pentisomicin, pentizi proinsulin human, proline, prolintane hydrochloride, pro done sodium, pentobarbital, pentomone, pentopril, pentosan, mazine hydrochloride, promethazine hydrochloride, pro pentostatin, pentoxifylline, pentrinitrol, pentroZole, peplo pafenone hydrochloride, propagermanium, propanidid, pro mycin Sulfate, pepstatin, perflubron, perfof amide, perfosfa pantheline bromide, proparacaine hydrochloride, propatyl mide, pergolide, perhexyline maleate, perillyl alcohol, perin nitrate, propentofylline, propenZolate hydrochloride, dopril, perindoprilat, perlapine, permethrin, peroSpirone, propikacin, propiomazine, propionic acid, propionylcar perphenazine, phenacemide, phenaridine, phenazinomycin, nitine, propiram, propiram-paracetamol, propiverine, propo phenaZopyridine hydrochloride, phenbutaZone sodium glyc fol, propoxycaine hydrochloride, propoxyphene hydrochlo erate, phencarbamide, phencyclidine hydrochloride, phen ride, propranolol hydrochloride, propulsid, propyl bis dimetrazine tartrate, phenelZine Sulfate, phenmetrazine acridone, propylhexedrine, propyliodone, propylthiouracil, hydrochloride, phenobarbital, phenoxybenzamine hydro produaZone, prorenoate potassium, proroxan hydrochloride, chloride, phenprocoumon, phenserine, phensuccinal, phen proscillaridin, prostalene, prostratin, protamine Sulfate, pro Suximide, phentermine, phentermine hydrochloride, phento tegrin, protirelin, protoSufloxacin, protriptyline hydrochlo lamine mesilate, phentoxifylline, phenyl aminosalicylate, ride, proxazole, proxazole citrate, proxicromil, proXorphan phenylacetate, phenylalanine, phenylalanyl ketoconazole, tartrate, prulifloxacin, pseudoephedrine hydrochloride, phenylbutaZone, phenylephrine hydrochloride, phenylpro desloratadine/pseudoephedrine Sulfate (commercially avail panolamine hydrochloride, phenylpropanolamine polistirex, able as CLARINEX-DR) from Merck), puromycin, purpu phenyramidol hydrochloride, phenyloin, phosphatase inhibi rins, pyrabrom, pyrantel, pamoate, pyrazinamide, pyrazofu tors, physostigmine, picenadol, picibanil, picotrin diolamine, rin, pyrazoloacridine, pyridostigmine bromide, pyrilamine picroliv, picumeterol, pidotimod, pifamine, pilocarpine, pil maleate, pyrimethamine, pyrinoline, pyrithione sodium, Sicamide, pimagedine, pimetine hydrochloride, pimilprost, pyrithione Zinc, pyrovalerone hydrochloride, pyroxamine pimobendan, pimozide, pinacidil, pinadoline, pindolol, pin maleate, pyrrocaine, pyrroliphene hydrochloride, pyrrolini nenol, pinocebrin, pinoxepin hydrochloride, pioglitaZone trin, pyrvinium pamoate, quadazocine mesylate, quazepam, (commercially available as ACTOSR) from Takeda Pharma quaZinone, quaZodine, quaZolast, quetiapine (commercially ceuticals), pipamperone, pipazethate, pipecuronium bro available as SEROQUEL(R) available from AstraZenica), qui mide, piperacetazine, piperacillin Sodium, piperamide male flapon, quinagolide, quinaldine blue, quinapril, quinaprilat, ate, piperazine, pipobroman, piposulfan, pipotiazine quinaZosin hydrochloride, quinbolone, quinctolate, quinde US 2014/0052264 A1 Feb. 20, 2014 camine acetate, quindonium bromide, quinelorane hydro Sorivudine, Sotalol, Soterenol hydrochloride, sparfloxacin, chloride, quinestrol, quinfamide, quingestanol acetate, sparfosate sodium, Sparfosic acid, sparsomycin, Sparteine quingestrone, quinidine gluconate, quinielorane hydrochlo Sulfate, spectinomycin hydrochloride, spicamycin D, spiper ride, quinine Sulfate, quinpirole hydrochloride, quinterenol one, spiradoline mesylate, spiramycin, spirapril hydrochlo Sulfate, quinuclium bromide, quinupristin, quipazine male ride, spiraprilat, spirogermanium hydrochloride, Spiromus ate, rabeprazole Sodium, racephenicol, racepinephrine, raf tine, Spironolactone, Spiroplatin, spiroXasone, splenopentin, antagonists, rafoxanide, ralitoline, raloxifene, raltitrexed, spongistatin 1, Sprodiamide, squalamine, stallimycin hydro ramatroban, ramipril, ramoplanin, ramosetron, ranelic acid, chloride, Stannous pyrophosphate, Stannous Sulfur colloid, ranimycin, ranitidine, ranolazine, rauwolfia Serpentina, stanozolol, statolon, staurosporine, stavudine, Steffimycin, recainam, recainam hydrochloride, reclazepam, Stenbolone acetate, Stepronin, Stilbazium iodide, stilonium regavirumab, regramostim, relaxin, relomycin, remacemide iodide, stipiamide, Stiripentol, Stobadine, streptomycin Sul hydrochloride, remifentanil hydrochloride, remiprostol, fate, Streptonicozid, streptonigrin, Streptozocin, Stromelysin remoxipride, repirinast, repromicin, reproterol hydrochlo inhibitors, strontium chloride Sr 89, succibun, succimer, suc ride, reserpine, resinferatoxin, resorcinol, retelliptine dem cinylcholine chloride. Sucralfate. Sucrosof ate potassium, ethylated, reticulon, reviparin Sodium, revizinone, rhenium re Sudoxicam, Sufentanil, Sufotidine, Sulazepam, Sulbactam piv 186 etidronate, rhizoxin, ribaminol, ribavirin, riboprine, oxil, Sulconazole nitrate, Sulfabenz, Sulfabenzamide, Sulfac ribozymes, ricasetron, ridogrel, rifabutin, rifametane, etamide, Sulfacytine, Sulfadiazine, Sulfadoxine, Sulfalene, rifamexil, rifamide, rifampin, rifapentine, rifaximin, retina Sulfamerazine, Sulfameter, Sulfamethazine, Sulfamethizole, mide, rilopiroX, riluzole, rimantadine, rimcazole hydrochlo Sulfamethoxazole, Sulfamonomethoxine, Sulfamoxole, Sulfa ride, rimexolone, rimiterol hydrobromide, rimoprogin, rio nilate Zinc, Sulfanitran, Sulfasalazine, Sulfasomizole, Sul dipine, rioprostil, ripazepam, ripisartan, risedronate Sodium, fazamet, Sulfinalol hydrochloride, Sulfinosine, Sulfinpyra risedronic acid, risocaine, risotilide hydrochloride, rispen Zone, Sulfisoxazole, Sulfomyxin, Sulfonterol hydrochloride, Zepine, risperdal, risperidone, ritanserin, ritipenem, ritodrine, Sulfoxamine, Sulinldac, Sulmarin, Sulnidazole, Suloctidil, ritolukast, ritonavir, rizatriptan benzoate, rocastine hydro Sulofenur, Sulopenem, Suloxifen oxalate, Sulpiride, Sulpros chloride, rocuronium bromide, rodocaine, roflurane, tone, Sultamicillin, Sulthiame, Sultopride, Sulukast, Sumaro rogletimide, rohitukine, rokitamycin, roletamicide, rolgami tene, Sumatriptan, Suncillin Sodium, Suproclone, Suprofen, dine, rolicyprine, rolipram, rollitetracycline, rolodine, romaz Suradista, Suramin, Surfomer, Suricamide maleate, SuritoZole, arit, romurtide, ronidazole, ropinirole (commercially avail Suronacrine maleate, Suxemerid Sulfate, Swainsonine, able as REQUIPR) from GlaxoSmithKline), ropitoin symakalim, symclosene, symetine hydrochloride, synthetic hydrochloride, ropivacaine, ropizine, roquinimex, rosarami glycosaminoglycans, tadalafil (commercially available as cin, roSoxacin, rotoxamine, rosuvastatin (commercially CIALIS(R) and ACIRCAR) from from Eli Lilly and Company), available as CRESTORR) available from AstraZeneca), taciamine hydrochloride, tacrine hydrochloride, tacrolimus, roXaitidine, roXarsone, roXindole, roXithromycin, rubiginone talampicillin hydrochloride, taleranol, talisomycin, tallimus B1, ruboxyl, rufloxacin, rupatidine, rutamycin, ruzadolane, tine, talmetacin, talniflumate, talopram hydrochloride, talos sabeluzole, Safingol, Safironil, Saintopin, Salbutamol, sal alate, tametraline hydrochloride, tamoxifen (commercially colex, Salethamide maleate, salicyl alcohol, salicylamide, available as NOLVADEXOR) from AstraZeneca), tampramine salicylate meglumine, Salicylic acid, Salmeterol, Salnacedin, fumarate, tamsulosin hydrochloride, tandamine hydrochlo Salsalate, sameridine, Sampatrilat, Sancycline, Sanfetrinem, ride, tandospirone, tapgen, taprostene, tasosartan, tauromus sanguinarium chloride, Saperconazole, saprisartan, saprop tine, taxane, taxoid, tazadolene Succinate, taZanolast, tazaro terin, saquinavir, Sarafloxacin hydrochloride, Saralasin tene, tazifylline hydrochloride, taZobactam, tazofelone, acetate, SarCNU, sarcophytol A, SargramoStim, Sarmoxicil tazolol hydrochloride, tebufelone, tebuquine, technetium Tc lin, Sarpicillin, Sarpogrelate, Saruplase, Saterinone, satigrel, 99 m bicisate, teclozan, tecogalan Sodium, teecleukin, teflu Satumomab pendetide, Schick test control, scopafungin, Sco rane, tegafur, tegretol, teicoplanin, telenzepine, tellurapyry polamine hydrobromide, ScraZaipine hydrochloride, Sdi 1 lium, telmesteine, telmisartan, telomerase inhibitors, telox mimetics, secalciferol, secobarbital. Seelzone, seglitide antrone hydrochloride, teludipine hydrochloride, acetate, selegiline, selegiline hydrochloride, selenium Sul temafloxacin hydrochloride, tematropium methyl sulfate, fide, selenomethionine se 75, selfotel, sematilide, semdu temazepam, temelastine, temocapril, temocillin, temoporfin, ramicin, semotiadil, Semustine, sense oligonucleotides, sepa temozolomide, tenofovir, tenidap, teniposide, tenosal, Zonium chloride, Seperidol hydrochloride, Seprilose, tenoxicam, tepirindole, tepoxalin, teprotide, teraZosin, ter seproxetine hydrochloride, seractide acetate, Sergolexole binafine, terbutaline sulfate (commercially available as BRI maleate, serine, sermetacin, sermorelin acetate, Sertacona CANYL(R) from AstraZeneca), terconazole, terfenadine, ter Zole, sertindole, Sertraline, Setiptiline, Setoperone, Sevirumab, flavoxate, terguride, teriparatide acetate, terlakiren, sevoflurane, Sezolamide, Sibopirdine, sibutramine hydrochlo terlipressin, terodiline, teroxalene hydrochloride, teroxirone, ride, signal transduction inhibitors, silandrone, Sildenafil tertatolol, tesicam, tesimide, testolactone, testosterone, tetra (commercially available as VIAGRAR) from Pfizer Inc.), sil caine, tetrachlorodecaoxide, tetracycline, tetrahydrozoline ipide, silteplase, silver nitrate, Simendan, SimtraZene, simv hydrochloride, tetramisole hydrochloride, tetrazolast meglu astatin (commercially available as ZOCORR) from Merck), mine, tetraZomine, tetrofosmin, tetroquinone, tetroXoprim, sincalide, sineflungin, sinitrodil, sinnabidol, sipatrigine, tetrydamine, thaliblastine, thalidomide, theofibrate, theo Sirolimus, Sisomicin, Sitogluside, sizofuran, Sobuzoxane, phylline, thiabendazole, thiamiprine, thiamphenicol, thiamy Sodium amylosulfate, Sodium iodide I 123, Sodium nitroprus lal, thiaZesim hydrochloride, thiazinamium chloride, thiazo side, Sodium oxybate, sodium phenylacetate, Sodium salicy lidinedione, thiethylperazine, thimerfonate Sodium, late, Solverol, Solypertine tartrate, Somalapor, Somantadine thimerosal, thiocoraline, thiofedrine, thioguanine, thiomar hydrochloride, Somatomedin B, Somatomedin C, somatrem, inol, thiopental Sodium, thioperamide, thioridazine, thiotepa, Somatropin, Somenopor, somidobove, Sonermin, Sorbinil, thiothixene, thiphenamil hydrochloride, thiphencillin potas US 2014/0052264 A1 Feb. 20, 2014

sium, thiram, thozalinone, threonine, thrombin, thrombopoi able as LEVITRAR) from GlaxoSmithKline), variolin B, etin, thrombopoietin mimetic, thymalfasin, thymopoietin vasopressin, Vecuronium bromide, Velaresol, Velnacrine receptor agonist, thymotrinan, thyromedan hydrochloride, maleate, Venlafaxine, Veradoline hydrochloride, Veramine, thyroxine 1 125, thyroxine 1131, tiacrilast, tiacrilast sodium, Verapamil hydrochloride, verdins, verilopam hydrochloride, tiagabine, tiamenidine, tianeptine, tiapafant, tiapamil hydro Verlukast, Verofylline, Veroxan, Verteporfin, Vesnarinone, chloride, tiaramide hydrochloride, tiazofurin, tibenelast vexibinol, Vidarabine, vigabatrin, viloxazine hydrochloride, Sodium, tibolone, tibric acid, ticabesone propionate, ticarbo vinblastine Sulfate, vinburnine citrate, Vincofos, Vinconate, dine, ticarcillin cresyl Sodium, ticlatone, ticlopidine, tic Vincristine Sulfate, vindesine, vindesine Sulfate, vinepidine Sulfate, Vinglycinate Sulfate, Vinleurosine Sulfate, vinorel rynafen, tienoxolol, tifurac sodium, tigemonam dicholine, bine, Vinpocetine, Vintoperol, Vinxaltine, Vinzolidine Sulfate, tigestol, tiletamine hydrochloride, tilidine hydrochloride, til Viprostol, Virginiamycin, viridofulvin, ViroXime, vitaxin, isolol, tilnoprofen arbamel, tillorone hydrochloride, tiludr Volazocine, Voriconazole, Vorozole, VOXergolide, warfarin onate disodium, tiludronic acid, timefurone, timobesone Sodium, Xamoterol, Xanomeline, XanoXate Sodium, Xanthinol acetate, timolol, tin ethyl etiopurpurin, tinabinol, tinidazole, niacinate, Xemilofiban, Xenalipin, Xenbucin, Xilobam, Ximo tinzaparin sodium, tioconazole, tiodaZosin, tiodonium chlo profen, Xipamide, Xorphanol mesylate, Xylamidine tosylate, ride, tioperidone hydrochloride, tiopinac, tioSpirone hydro xylazine hydrochloride, Xylometazoline hydrochloride, chloride, tiotidine, tiotropium bromide, tioxidazole, tipen Xylose, yangambin, Zabicipril, Zacopride, Zafirlukast, Zalcit tosin hydrochloride, tipredane, tiprenolol hydrochloride, abine, Zaleplon, Zalospirone, Zaltidine hydrochloride, Zalto tiprinast meglumine, tipropidil hydrochloride, tiqueside, profen, Zanamivir, Zankiren, Zanoterone, Zantac, Zarirlukast, tiquinamide hydrochloride, tirandalydigin, tirapazamine, tir Zatebradine, Zatosetron, Zatosetron maleate, Zenarestat, Zena ilazad, tirofiban, tiropramide, titanocene dichloride, tixanox, Zocine mesylate, Zeniplatin, Zeranol, Zidometacin, Zidovu tiXocortol pivalate, tizanidine hydrochloride, tobramycin, dine, Zifrosilone, Zilantel, Zilascorb, Zileuton, Zimeldine tocainide, tocamphyl, tofenacin hydrochloride, tolamolol. hydrochloride, Zinc undecylenate, Zindotrine, Zinoconazole tolazamide, tolazoline hydrochloride, tolbutamide, tolca hydrochloride, Zinostatin, Zinterol hydrochloride, Zin pone, tolciclate, tolfamide, tolgabide, lamotrigine, tolimi ViroXime, Ziprasidone, Zobolt, Zofenopril calcium, Zofenop done, tolindate, tolmetin, tolnaftate, tolpovidone 1 131, rilat, Zolamine hydrochloride, Zolazepam hydrochloride, tolpyrramide, tolrestat, tomelukast, tomoxetine hydrochlo Zoledronie acid, Zollertine hydrochloride, Zolmitriptan, Zolpi ride, tonazocine mesylate, topiramate, topotecan, topotecan dem, Zomepirac sodium, Zometapine, ZonicleZole hydrochlo hydrochloride, top sentin, topterone, toguizine, torasemide, ride, Zonisamide, Zopiclone, Zopolrestat, Zorbamycin, Zoru toremifene, torsemide, tosifen, tosufloxacin, totipotent stem bicin hydrochloride, Zotepine, Zucapsaicin, JTT-501 (PNU cell factor, tracazolate, trafermin, tralonide, tramadol hydro 182716) (reglitazar), AR-HO39122, MCC-555 chloride, tramazoline hydrochloride, trandolapril, tranex (netoglitazone), AR-HO49020 (tesaglitazar), CS-011 (CI amic acid, tranilast, transcamide, translation inhibitors, tras 1037), GW-409544x, KRP-297, RG-12525, BM-15.2054, tuzumab (commercially available as HERCEPTINR) from CLX-0940, CLX-0921, DRF-2189, GW-1929, GW-9820, Genentech), traXanox, traZodone hydrochloride, traZodone LR-90, LY-510929, NIP-221, NIP-223, JTP-20993, LY hcl, trebenzomine hydrochloride, trefentanil hydrochloride, 29311 Na, FK 614, BMS 298.585, R 483, TAK 559, DRF treloxinate, trepipam maleate, trestolone acetate, tretinoin, 2725 (ragaglitazar), L-686398, L-168049, L-805645, triacetin, triacetyluridine, triafungin, triamcinolone, triampy L-054852, demethyl asteriquinone B1 (L-783281), Zine Sulfate, triamterene, triazolam, tribenoside, tricaprilin, L-363586, KRP-297, P32/98, CRE-16336, EML-1625, phar tricetamide, trichlormethiazide, trichohyalin, triciribine, maceutically acceptable salts thereof (e.g., Zn, Fe,Mg, K, Na, tricitrates, triclofenol piperazine, triclofos sodium, triclonide, trientine, trifenagrel, triflavin, triflocin, triflubazam, triflumi F, CI, Br, I, acetate, diacetate, nitrate, nitrite, sulfate, sulfite, date, trifluoperazine hydrochloride, trifluperidol, triflupro phosphate, and phosphite salts), pharmaceutically acceptable mazine, triflupromazine hydrochloride, trifluridine, trihex forms thereof with acid associates (e.g. HCl), and any com yphenidyl hydrochloride, triloStane, trimaZosin bination thereof. hydrochloride, trimegestone, trimeprazine tartrate, tri 0054 Porous implants of the present invention may, in methadione, trimethaphan camsylate, trimethobenzamide Some embodiments, comprise a plurality of polymeric par hydrochloride, trimethoprim, trimetozine, trimetrexate, ticles sintered together at a plurality of contact points so as to trimipramine, trimoprostil, trimoxamine hydrochloride, tri form a porous network, at least one antioxidant, and option olein 1 125, triolein 1131, trioxifene mesylate, tripamide, ally further comprise at least one growth factor, wherein the tripelennamine hydrochloride, triprolidine hydrochloride, antioxidant and the growth factor are independently adsorbed triptorelin, trisulfapyrimidines, troclosene potassium, trogli to a Surface of at least a portion of the polymeric particles taZone, trolamine, troleandomycin, trombodipine, trometa and/or disposed in a pore of the porous network. mol, tropanserin hydrochloride, tropicamide, tropine ester, 0055 Growth factors may be useful in directing or tropisetron, trospectomycin, trovafloxacin, troVirdine, tryp enhancing cell growth on and/or through the porous implant. tophan, tuberculin, tubocurarine chloride, tubulozole hydro Examples of growth factors Suitable for use in conjunction chloride, tucarcsol, tulobuterol, turosteride, tybamate, tylo with the porous implants of the present invention may, in genin, tyropanoate Sodium, tyrosine, tyrothricin, tyrphostins, Some embodiments, include, but are not limited to, adrenom ubenimex, uldazepam, undecylenic acid, uracil mustard, ura edulin (AM), angiopoietin (Ang), bone morphogenetic pro pidil, urea, uredepa, uridine triphosphate, urofollitropin, teins (BMPs), epidermal growth factor (EGF), erythropoietin urokinase, ursodiol, Valaciclovir, Valine, Valnoctamide, Val (EPO), fibroblast growth factor (FGF), granulocyte colony proate Sodium, Valproic acid, Valsartan (commercially avail stimulating factor (G-CSF), granulocyte macrophage colony able as DIOVANR) from Novartis Pharmaceuticals), vamica stimulating factor (GM-CSF), hepatocyte growth factor mide, Vanadeine, Vancomycin, Vaminolol, Vapiprost (HGF), hepatoma-derived growth factor (HDGF), insulin hydrochloride, vapreotide, Vardenafil (commercially avail like growth factor (IGF), migration-stimulating factor, nerve US 2014/0052264 A1 Feb. 20, 2014 growth factor (NGF) and other neurotrophins, platelet-de ally further comprise at least one pigment and/or dye, wherein rived growth factor (PDGF), transforming growth factor the antioxidant and the pigment and/or dye are independently alpha (TGF-C.), transforming growth factor beta (TGF-B). adsorbed to a surface of at least a portion of the polymeric tumor necrosis factor-alpha (TNF-C), vascular endothelial particles and/or disposed in a pore of the porous network. growth factor (VEGF), interleukin-1 (IL-1), IL-2, IL-3, Examples of pigments and/or dyes Suitable for use in con IL-4, IL-5, IL-6, IL-7, and the like, any derivative thereof, and junction with the porous implants described herein may, in any combination thereof. Some embodiments, include, but are not limited to, inorganic 0056 Porous implants of the present invention may, in based colorants, organic-based colorants, and the like, and Some embodiments, comprise a plurality of polymeric par any combination thereof. ticles sintered together at a plurality of contact points so as to 0062. In some embodiments, any of the foregoing addi form a porous network, at least one antioxidant, and option tives (APIs, growth factors, cells and cell-like structures, ally further comprise at least one cell or cell-like structure, imaging agents, pigments and/or dyes, and the like) may be wherein the antioxidant and the cell or cell-like structure are independently included in the porous implants of the present independently adsorbed to a surface of at least a portion of the invention in an amount ranging from a lower limit of about polymeric particles and/or disposed in a pore of the porous 0.001%, 0.01%, 0.05%, 0.1%, 0.5%, or 1% to an upper limit network. of about 10%. 5%.3%.2%, or 1% by weight of the polymer, 0057 Cells or cell-like structures may be useful in miti and wherein the amount may range from any lower limit to gating rejection of the porous implant and hastening patient any upper limit and encompass any Subset therebetween. The recovery. Examples of cell or cell-like structure suitable for amount of each additive may depend on a number of factors use in conjunction with the porous implants of the present that include, interalia, the application of the porous implant, invention may, in some embodiments, include, but are not the composition of the antioxidant, the composition of the limited to, endothelial cells, hepatic cells, myocytes, Smooth additive, and the composition of the polymeric particles uti muscle cells, nerve cells, progenitor cells, stem cells, parthe lized in conjunction with the porous implant. nogenetic stem cell, activated version thereof (e.g., those 0063. In some embodiments, the porous implants of the overexpressing a marker), deactivated version thereof (e.g., present invention may comprise a porous network described those underexpressing a marker), Synthetic cells, and the like. herein, antioxidants, and optionally further comprise a rein In some embodiments, cells may be from the patient, animal forcing structure in contact with at least a portion of the (e.g., pig), or another Suitable donor. porous network. In some embodiments, the porous network 0058 Porous implants of the present invention may, in may be disposed on at least a portion of a surface of a rein Some embodiments, comprise a plurality of polymeric par forcing structure so as to leave a second portion of the rein ticles sintered together at a plurality of contact points so as to forcing structure exposed to the local environment. In some form a porous network, at least one antioxidant, and option embodiments, the porous network may be disposed about a ally further comprise at least one imaging agent, wherein the reinforcing structure. It should be noted that as used herein, antioxidant and the imaging agent are independently the term “exposed to the local environment” refers to being adsorbed to a surface of at least a portion of the polymeric immediately exposed to a local environment (e.g., being able particles and/or disposed in a pore of the porous network. As to be touched) as opposed to requiring the local environment used herein, the term "imaging agent” refers to a molecule, to penetrate the porous network to access the object of inter compound, or particle that interacts with electromagnetic est. Exposure to the local environment may beachieved by at radiation to enable one to ascertain an image. least one of protruding from the porous network, being dis 0059 Examples of imaging agents suitable for use in con posed on the Surface of the porous network, and any hybrid junction with the porous implants described herein may, in thereof. Some embodiments, include, but are not limited to, magnetic 0064 Reinforcing structures may, in some embodiments, resonance imaging agents (e.g., barium Sulfate, iron oxide inter alia, enhance the mechanical strength of the porous particles, gadolinium compounds, erbium compounds, gado implant of the present invention, enable post-production linium endofullerenes, and gadolinium endonanotubes), shaping of the porous implant of the present invention, enable X-ray imaging agents (e.g., barium sulfate, iodine com securing of the porous implant to another object (e.g., a bone). pounds, and iodine endonanotubes), ultrasound imaging In some embodiments, securing may be achieved, for agents (e.g., perfluorocarbons and air bubbles), near infrared example, with at least one of adhesives, Screws, bone anchors, imaging agents (e.g., carbon nanotubes, gold nanoparticles, tacks, wires, Sutures, Stitches, and the like, any hybrid thereof, silver nanoparticles, and gold nanoshells), bismuth com and any combination thereof. pounds, tungsten compounds, and the like, and any combina 0065 Reinforcing structures suitable for use in conjunc tion thereof. tion with porous implants of the present invention may, in 0060. In some embodiments, imaging agents may be use Some embodiments, comprise metals (e.g., titanium), metal ful in monitoring the condition of the porous implants of the alloys (e.g., cobalt chromium alloys and trabecular metal), present invention (or the polymeric particles thereof) over the ceramics, and the like, and any combination thereof. Rein long-term. By way of nonlimiting example, an imaging agent forcing structures Suitable for use in conjunction with the disposed on the Surface of the polymeric particles near the porous implants of the present invention may, in some Surface of the porous implant may be useful for noninvasively embodiments, be in the form of a rod, a tube, wire, mesh, a monitoring degradation (e.g., physical wear) of the porous sheet, and the like, and any hybrid thereof. implant. 0066. In some embodiments, the porous implants of the 0061 Porous implants of the present invention may, in present invention may comprise a porous network described Some embodiments, comprise a plurality of polymeric par herein, antioxidants, and optionally further comprise a skin ticles sintered together at a plurality of contact points so as to layer disposed on at least a portion of a Surface of the porous form a porous network, at least one antioxidant, and option network. Skin layers may be advantageous as a Smooth Sur US 2014/0052264 A1 Feb. 20, 2014 face of the porous implant so as to minimize wear of the and/or skin layers as described herein, may optionally be porous implant and/or abrasion of the adjacent tissue or bone. designed to be reshaped post-production, or any combination Skin layers suitable for use in conjunction with porous thereof. implants of the present invention may, in Some embodiments, 0071 Porous implants of the present invention may, in be in the form of a film, a mesh, a patch, a net, and the like. Some embodiments, be used as a craniomaxillofacial implant 0067. Skin layers suitable for use in conjunction with for implantation in the mouth, jaw, face, skull, nose, ear, chin, porous implants of the present invention may, in some cheek, neck, ocular Socket, cranium, larynx, lips, nasal, man embodiments, comprise other polyethylenes (e.g., linear low dible, orbital, or associated structures. density polyethylenes (LLDPE), low density polyethylenes 0072 By way of a nonlimiting example illustrated in (LDPE), and high density polyethylene (HDPE)), polypropy FIGS. 3A-B, a porous implant of the present invention may, in lenes, ethylene-propylene copolymers, graft-modified olefin some embodiments, be a cranial implant 300 that comprises polymers, chlorinated polyethylenes, thermoplastic Vulcani porous network 310 having skin layer 312 that is shaped to fit Zates polyisoprenes, polyesters, polyamides, ethylene vinyl into cranial deformation 322 of cranium302. As illustrated in acetate copolymers, ethylene vinyl-methacrylate copoly FIG. 3B cranial implant 300 is secured in cranial deformation mers, silicones, polyethylene glycols, poly lactic acid, poly 304 with an adhesive disposed therebetween. glycolic acid, polyethylene imine, polyurethanes, polyacry 0073. By way of another nonlimiting example illustrated lonitrile, styrene block copolymers, rubbers, ethylene-car in FIG. 4A, a porous implant of the present invention may, in boxylic acid copolymers, ethylene acrylate copolymers, some embodiments, bean orbital reconstruction implant 400. polybutylene, polybutadiene, nylons, polycarbonates, ethyl FIG. 4B illustrates an example cross-section of the orbital ene ethylacrylate polymers (EEA), ethylene styrene inter reconstruction implant 400 having a porous network 410 polymers (ESI), and the like, any derivative thereof, any disposed about a reinforcing mesh 414. FIG. 4C illustrates an copolymer thereof, and any combination thereof. example of a reinforcing mesh 414 that includes several optional Securing components 420, 422,424, 428 that may be 0068. In some embodiments, the porous implants of the part of reinforcing mesh 414 as illustrated in securing com present invention may have any desired shape. As should be ponent 420 or extend from and connect to reinforcing mesh recognized by one of ordinary skill in the art, the desired 414 as illustrated in securing components 422, 424, 428. shape may depend on, interalia, the application in which the 0074 By way of yet another nonlimiting example illus porous implants of the present invention are utilized. trated in FIG. 5, porous implant of the present invention may, 0069. In some embodiments, the porous implants of the in some embodiments, be a mandible implant 500. As illus present invention may be designed to be reshaped post-pro trated, mandible implant 500 comprises porous network 510 duction (e.g., before implantation). Reshaping may be with structural plate 514 at the interface of the mandible achieved by heating the porous implant and remodeling, gen implant 500 and the mandible 502. Further, mandible implant erally by hand. Reshaping may further be achieved by cutting 500 is secured to the mandible 502 with screw 520 that or the like. One skilled in the art with the benefit of this extends through the porous network 510 and the structural disclosure would understand that because the polymeric par plate 514. ticles are sintered together, the ability to reshape the porous 0075. As will be apparent to one of ordinary skill in the art, implant may be minimal, that is, allowing for minor adjust the above examples and corresponding figures are not limit ments in the shape So as to conform to the patient. ing of the present invention as to, interalia, the configurations 0070 Porous implants described herein may, in some of a porous implant and its potential implementation. embodiments, comprise at least one plurality of polymeric 0076. In some embodiments, forming porous implants of particles (each independently having a characteristic or com the present invention may involve heating a plurality of poly bination of characteristics described herein, e.g., polymer meric particles described herein in a mold so as to sinter composition, polymer average molecular weight, shape, together the polymeric particles at a plurality of contact diameter in at least one dimension, Surface roughness, bulk points thereby forming a porous network; and contacting the density, and any combination thereof) sintered together at a polymeric particles with an antioxidant. In some embodi plurality of contact points so as to form a porous network ments, contacting may occur before and/or after heating. (having a characteristic or combination of characteristics 0077. In some embodiments, forming porous implants of described herein, e.g., porosity, average diameter of pores, the present invention may involve heating while applying and any combination thereof) and at least one antioxidant pressure to a plurality of polymeric particles described herein described herein in an amount described herein, wherein the in a mold so as to sinter together the polymeric particles at a antioxidant is adsorbed to a Surface of at least a portion of the plurality of contact points thereby forming a porous network; polymeric particles and/or disposed in a pore of the porous and contacting the polymeric particles with an antioxidant. network. In some embodiments, a porous implant described 0078. One skilled in the art with the benefit of this disclo herein may optionally further comprise at least one of at least Sure should understand that the temperature and pressure one API described herein, at least one growth factor described used in conjunction with forming porous networks described herein, at least one cell or cell-like structure described herein, herein should be a combination to a temperature and a pres at least one imaging agent described herein, at least one Sure Suitable for fusing the polymeric particles at a plurality of pigment and/or dye described herein, each of which may contact points so as to form a porous network and not sinter independently be in an amount described herein, and wherein the polymeric particles to the extent that a nonporous, Solid the antioxidant is adsorbed to a surface of at least a portion of mass is formed. One skilled in the art with the benefit of this the polymeric particles and/or disposed inapore of the porous disclosure should also recognize that the temperature and network. Further, in some embodiments, porous implants pressure used in forming porous networks described herein described herein may have any desired shape, may optionally will be dependent on, interalia, the geometry of the mold, the further comprise reinforcing structures as described herein processing time, the composition of the polymeric particles, US 2014/0052264 A1 Feb. 20, 2014 the composition of an antioxidant included during the mold embodiments, more than one doping procedure may be per ing process, the desired porosity of the porous network pro formed. In some embodiments, doping may occur while the duced, and the like. porous network is in the mold. In some embodiments, doping 007.9 For example, temperatures suitable for use in con may occur after the porous network has been removed from junction with forming porous networks described herein may, the mold. in Some embodiments, be at the softening temperature of the I0086. It should be noted that doping includes, but is not polymer of the polymeric particles, as appropriate. As used limited to, applying, dipping, immersing. Submerging, Soak herein, the term “softening temperature” refers to the tem ing, rinsing, Washing, painting, coating, showering, drizzling, perature above which a material becomes pliable, which is spraying, placing, dusting, sprinkling, affixing, and any com typically below the melting point of the material. In some bination thereof. Further, it should be noted that applying embodiments, forming porous networks described herein includes, but is not limited to, Surface treatments, infusion may occurattemperatures ranging from a lower limit of about treatments where the antioxidants and/or additives described 90°C., 100° C., 110° C., 120° C., 130° C., 140°C., 150° C., hereinbecome disposed in at least a portion of the pores of the 160° C. 170° C., or 180°C. oran upper limit of about 300° C., porous network, or any combination thereof. 275° C., 250° C., 225°C., 200° C. 175° C., or 150° C., and wherein the temperature may range from any lower limit to I0087. In some embodiments, doping may occur over a any upper limit and encompass any Subset therebetween. It prolonged period of time. For example, doping a porous should be noted that forming methods that utilize increased network with cells may occur over several days. pressure may, in some embodiments, enable forming porous I0088. In some embodiments, a porous implant of the networks described herein at lower temperatures. present invention may be implanted in and/or used in con 0080. In some embodiments, the polymeric particles may junction with the treatment of a patient. As used herein, the be preheated before introduction into the mold. Preheating terms “subject' and “patient” are used interchangeably and may advantageously minimize the time to form the porous refer to both human and nonhuman animals and insects. The network. In some embodiments, the polymeric particles may term “nonhuman animals' as used herein includes all verte be preheated to a temperature below the Softening tempera brates, e.g., mammals and non-mammals, such as nonhuman ture of the polymer of the polymeric particles. In some primates, mice, rats, sheep, dogs, cats, horses, cows, chick embodiments, polymeric particles may be preheated to a tem ens, amphibians, fish, reptiles, and the like. The term perature about 10%, about 5%, or about 1% below the soft “insects' as used herein includes all arthropods, e.g., bees, ening temperature of the polymeric particles. In some flies, Drosophila flies, beetles, spiders, and the like. embodiments, the polymeric particles may be preheated to a I0089. In some embodiments, implantation into a patient temperature about 10°C. below, about 5°C. below, or about may involve securing the porous implant to a bone. 1° C. below the softening temperature of the polymeric par 0090. In some embodiments, porous implants of the ticles. present invention may be included in a kit that also includes a 0081. In some embodiments, a reinforcing structure and/ set of instructions. In some embodiments, a kit may comprise or a skin layer may be included in the mold when forming the a porous implant of the present invention and an article for porous network. In some embodiments, a reinforcing struc securing the implant within the patient. ture and/or a skin layer may be adhered to a porous network after having been formed. 0091 To facilitate a better understanding of the present 0082 In some embodiments, molds used in conjunction invention, the following examples of preferred or representa with forming porous networks described herein may be at tive embodiments are given. In no way should the following least partially lined release agents. Release agents may examples be read to limit, or to define, the scope of the advantageously ease removal of porous networks from the invention. mold. 0083 Release agents suitable for use in conjunction with EXAMPLES forming porous networks described herein may be chemical release agents or physical release agents. Nonlimiting Example 1 examples of chemical release agents may, in Some embodi ments, include, but are not limited to, oils, oil-based solutions 0092. Several porous samples were prepared by heating and/or Suspensions, Soapy solutions and/or Suspensions, coat various samples of UHMWPE particulates (as described in ings bonded to the mold Surface, and the like, and any com Table 1) while in a correspondingly sized mold. The physical bination thereof. Nonlimiting examples of physical release properties of the resultant samples were analyzed and are agents may, in some embodiments, include, but are not lim reported in Table 2. ited to, papers, plastics, and the like, and any combination thereof. TABLE 1 0084. In some embodiments, porous implants or a com Viscosity ponent thereof (e.g., the porous network or a reinforcing Number Melt Flow Index** Average Particle structure) may be cut and/or molded after production to yield (ml/g) (g 10 min) Size: * (microns) a desired shape. Cutting and/or molding may occur, in some UHMWPE-1 2250 --0 35 embodiments, at any Suitable time, for example, before pack UHMWPE-2 3800 --0 65 aging or before implantation. UHMWPE-3 2100 --0 120 UHMWPE-4 2250 --0 140 0085. In some embodiments, forming porous implants of UHMWPE-5 1OOO --0 150 the present invention may involve doping the porous network UHMWPE-6 2200 --0 175 after having been formed with antioxidants, additives UHMWPE-7 2OOO --0 28O described herein, and any combination thereof. In some US 2014/0052264 A1 Feb. 20, 2014

TABLE 1-continued patent or other documents that may be incorporated herein by reference, the definitions that are consistent with this speci Viscosity fication should be adopted. Number Melt Flow Index Average Particle The invention claimed is: (ml/g) (g 10 min) Size: * (microns) 1. A porous implant comprising: UHMWPE-8 550 1.8 120 a plurality of polymeric particles sintered together at a UHMWPE-9 470 1.1 118 plurality of contact points to form a porous network UHMWPE-10 360 3.5 220 having pores, the plurality of polymeric particles com *As measured by DIN EN ISO 1628. prising polyethylene; and **As measured by EN ISO 1133 at 190° C. 21.6 kg. an antioxidant disposed on a Surface of at least some of the *** As measured by laser diffraction. polymeric particles and/or in the pore of the porous network. 2. The porous implant of claim 1 further comprising a TABLE 2 second plurality of polymeric particles comprising a polymer Pressure Drop Avg. Pore Size * selected from the group consisting of a polyethylene (mbar) (microns) Strength ** (MPa) polypropylene copolymer, a polyethylene-polybutylene UHMWPE-1 30 2O 1.7 copolymer, polytetrafluoroethylene, and expanded polytet UHMWPE-2 75 15 2.5 rafluoroethylene. UHMWPE-3 40 25 2.5 3. The porous implant of claim 1, wherein at least a plural UHMWPE-4 10 52 <1 UHMWPE-5 2O 40 4.5 ity of the polymeric particles have a shape selected from the UHMWPE-6 2O 33 1.8 group consisting of spherical, ovular, Substantially spherical, UHMWPE-7 8 60 2.3 Substantially ovular, prolate spheroidal, popcorn, Substan UHMWPE-8 2O 40 >6 tially popcorn, potato, Substantially potato, discus, platelet, UHMWPE-9 2O 50 >8 flake, ligamental, acicular, fibrous, polygonal, randomly UHMWPE-10 15 130 >8 shaped, faceted, and any hybrid thereof, and the like with As measured using a sample of the porous article having a diameter of 140 mm, a width of 6.2-6.5 mm (depending on shrinkage), and an airflow rate of 7.5 mhour and measuring the rounded corners and/or edges. drop in pressure in mbar across the width of the sample, 4. The porous implant of claim 1, wherein the polyethylene **As measured by HgIntrusion DIN 133. comprises at least one selected from the group consisting of *** As measured by DIN EN ISO 178. high molecular weight polyethylene, very-high molecular weight polyethylene, ultrahigh molecular weight polyethyl 0093. Therefore, the present invention is well adapted to ene, and any combination thereof. attain the ends and advantages mentioned as well as those that 5. The porous implant of claim 1, wherein the polymeric are inherent therein. The particular embodiments disclosed particles have a bulk density of about 0.10 g/cm to about 0.98 above are illustrative only, as the present invention may be g/cm. modified and practiced in different but equivalent manners 6. The porous implant of claim 1, wherein the at least some apparent to those skilled in the art having the benefit of the of the polymeric particles have a diameter in at least one teachings herein. Furthermore, no limitations are intended to dimension ranging from about 10 microns to about 5000 the details of construction or design herein shown, other than microns. as described in the claims below. It is therefore evident that 7. The porous implant of claim 1, wherein the porous the particular illustrative embodiments disclosed above may network comprises pores having a diameter of about 15 be altered, combined, or modified and all such variations are microns to about 500 microns. considered within the scope and spirit of the present inven 8. The porous implant of claim 1, wherein the porous tion. The invention illustratively disclosed herein suitably network has a porosity of about 40% to about 90%. may be practiced in the absence of any element that is not 9. The porous implant of claim 1, wherein at least some of specifically disclosed herein and/or any optional element dis the polymeric particles have a Surface that is about nano closed herein. While compositions and methods are described rough to about micro-rough. in terms of "comprising.” “containing,” or “including vari 10. The porous implant of claim 1, wherein the antioxidant ous components or steps, the compositions and methods can comprises at least one selected from the group consisting of also “consist essentially of or “consist of the various com anthocyanin, ascorbic acid, glutathione, lipoic acid, uric acid, ponents and steps. All numbers and ranges disclosed above resveratrol, flavonoids, carotenes, carotenoids, tocopherols, may vary by Some amount. Whenever a numerical range with tocotrienols, ubiquinol, melatonin, secondary aromatic a lower limit and an upper limit is disclosed, any number and amines, benzofuranones, hindered phenols, polyphenols, and any included range falling within the range is specifically any combination thereof. disclosed. In particular, every range of values (of the form, 11. The porous implant of claim 1, wherein the antioxidant “from about a to about b,” or, equivalently, “from approxi is present in an amount ranging from about 0.01% to about mately a to b,” or, equivalently, “from approximately a-b) 10% by weight of the polyethylene. disclosed herein is to be understood to set forth every number 12. The porous implant of claim 1 further comprising: and range encompassed within the broader range of values. an additive disposed on a Surface of at least some of the Also, the terms in the claims have their plain, ordinary mean polymeric particles and/or disposed in a pore of the ing unless otherwise explicitly and clearly defined by the porous network, the additive being selected from the patentee. Moreover, the indefinite articles “a” or “an,” as used group consisting of active pharmaceutical ingredients, in the claims, are defined hereinto mean one or more than one growth factors, cells or cell-like structures, imaging of the element that it introduces. If there is any conflict in the agents, pigments, dyes, and the like, and any combina usages of a word or term in this specification and one or more tion thereof. US 2014/0052264 A1 Feb. 20, 2014 17

13. The porous implant of claim 1 further comprising: 29. The porous implant of claim 19 further comprising: a reinforcing structure in contact with at least a portion of a reinforcing structure in contact with at least a portion of the porous network. the porous network. 14. The porous implant of claim 1 further comprising: 30. The porous implant of claim 19 further comprising: a skin layer disposed on at least a portion of a Surface of the a skin layer disposed on at least a portion of a Surface of the porous network. porous network. 15. The porous implant of claim 1, wherein at least a 31. The porous implant of claim 19, wherein at least a portion of the Surgical implant is adapted to receive a Surgical portion of the Surgical implant is adapted to receive a Surgical screw or Surgical bone anchor. screw or Surgical bone anchor. 16. A kit comprising the porous implant of claim 1 and a set 32. A kit comprising the porous implant of claim 19 and a of instructions. set of instructions. 17. A kit comprising the porous implant of claim 1 and a 33. A kit comprising the porous implant of claim 19 and a component capable of securing the porous implant to a bone. component capable of securing the porous implant to a bone. 18. A method comprising implanting the porous implant of 34. A method comprising implanting the porous implant of claim 1 into a patient. claim 19 into a patient. 19. A porous implant comprising: 35. A method of forming a porous implant, the method a plurality of polymeric particles sintered together at a comprising: plurality of contact points to form a porous network heating a plurality of polymeric particles in a mold so as to having pores, the plurality of polymeric particles com sinter together the polymeric particles at a plurality of prising a polymer selected from the group consisting of contact points thereby forming a porous network, the a polyethylene-polypropylene copolymer, a polyethyl plurality of polymeric particles comprising polyethyl ene-polybutylene copolymer, polytetrafluoroethylene, ene; and and expanded polytetrafluoroethylene; and contacting the polymeric particles with an antioxidant. an antioxidant disposed on a Surface of at least some of the polymeric particles and/or in the pore of the porous 36. The method of claim 35, wherein contacting occurs network. before heating. 20. The porous implant of claim 19, wherein the at least one 37. The method of claim 35, wherein contacting occurs polymer comprises at least one selected from the group con after heating. sisting of a high molecular weight polymer, a very-high 38. The method of claim 35 further comprising: molecular weight polymer, an ultrahigh molecular weight placing a reinforcing structure in the mold such that poly polymer, and any combination thereof. meric particles are disposed about at least a portion of a 21. The porous implant of claim 19, wherein the polymeric Surface of the reinforcing structure. particles have a bulk density of about 0.10 g/cm to about 0.98 39. The method of claim 35 further comprising: g/cm. applying pressure during heating. 22. The porous implant of claim 19, wherein the at least 40. The method of claim 35, wherein heating is to a tem Some of the polymeric particles have a diameter in at least one perature between about 90° C. and about 300° C. dimension ranging from about 10 microns to about 5000 41. The method of claim 35 further comprising: microns. cutting the porous structure to a desired shape. 23. The porous implant of claim 19, wherein the porous 42. The method of claim 35 further comprising: network comprises pores having a diameter of about 15 applying additional heat to the porous structure and reshap microns to about 500 microns. ing the porous structure into a desired shape. 24. The porous implant of claim 19, wherein the porous 43. A method of forming a porous implant, the method network has a porosity of about 40% to about 90%. comprising: 25. The porous implant of claim 19, wherein at least some heating a plurality of polymeric particles in a mold so as to of the polymeric particles have a surface that is about nano sinter together the polymeric particles at a plurality of rough to about micro-rough. contact points thereby forming a porous network, the 26. The porous implant of claim 19, wherein the antioxi plurality of polymeric particles comprising a polymer dant comprises at least one selected from the group consisting Selected from the group consisting of a polyethylene of anthocyanin, ascorbic acid, glutathione, lipoic acid, uric polypropylene copolymer, a polyethylene-polybutylene acid, resveratrol, flavonoids, carotenes, carotenoids, toco copolymer, polytetrafluoroethylene, and expanded pherols, tocotrienols, ubiquinol, melatonin, secondary aro polytetrafluoroethylene; and matic amines, benzofuranones, hindered phenols, polyphe contacting the polymeric particles with an antioxidant. nols, and any combination thereof. 44. The method of claim 43, wherein contacting occurs 27. The porous implant of claim 19, wherein the antioxi before heating. dant is present in an amount ranging from about 0.01% to 45. The method of claim 43, wherein contacting occurs about 10% by weight of the at least one polymer. after heating. 28. The porous implant of claim 19 further comprising: 46. The method of claim 43 further comprising: an additive disposed on a Surface of at least Some of the placing a reinforcing structure in the mold Such that poly polyethylene particles and/or disposed in a pore of the meric particles are disposed about at least a portion of a porous network, the additive being selected from the Surface of the reinforcing structure. group consisting of active pharmaceutical ingredients, 47. The method of claim 43 further comprising: growth factors, cells or cell-like structures, imaging applying pressure during heating. agents, pigments and/or dyes, and the like, and any com 48. The method of claim 43, wherein heating is to a tem bination thereof. perature between about 90° C. and about 300° C. US 2014/0052264 A1 Feb. 20, 2014

49. The method of claim 43 further comprising: 54. A method for structurally modifying a portion of a cutting the porous structure to a desired shape. cranium, the method comprising: 50. The method of claim 43 further comprising: implanting a porous Surgical implant into a cranium, the applying additional heat to the porous structure and reshap porous Surgical implant comprising: ing the porous structure into a desired shape. a porous structure formed from a plurality of polymeric 51. A method for structurally modifying a portion of a particles sintered at a plurality of contact points, the cranium, the method comprising: plurality of polymeric particles comprising a polymer implanting a porous Surgical implant into a cranium, the selected from the group consisting of a polyethylene porous Surgical implant comprising: polypropylene copolymer, a polyethylene-polybuty a porous structure formed from a plurality of polymeric lene copolymer, polytetrafluoroethylene, and particles sintered at a plurality of contact points, the expanded polytetrafluoroethylene; and plurality of polymeric particles comprising polyeth an antioxidant. ylene, and an antioxidant. 55. The method of claim 54 wherein the porous surgical 52. The method of claim 51 wherein the porous surgical implant further comprises a reinforcing structure. implant further comprises a reinforcing structure. 56. The method of claim 54, where implanting involves 53. The method of claim 51, where implanting involves securing the porous Surgical implant to a bone. securing the porous Surgical implant to a bone. k k k k k