Ann. N.Y. Acad. Sci. ISSN 0077-8923

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: Pharmaceutical Science to Improve the Human Condition: Prix Galien 2014

 The development of SERI R Surgical Scaffold, an engineered biological scaffold

Mark Jewell,1 William Daunch,2 Bradley Bengtson,3 and Enrico Mortarino2 1Division of Plastic , Oregon Health & Science University, Portland, Oregon. 2Allergan, Inc., Medford, Massachusetts. 3Bengtson Center for Aesthetics and Plastic Surgery and Associate Professor, Michigan State University, Grand Rapids, Michigan

Address for correspondence: Mark Jewell, M.D., 10 Coburg Rd, Suite 300, Eugene, OR 97401. [email protected]

The primary goal of reconstructive and revision surgery is to restore, repair, rebuild, and support damaged, weakened, or absent tissue. There are numerous approaches for support and repair, including the use of autologous tissue, human- or animal-derived acellular dermal matrices, absorbable or permanent synthetic mesh, and, now, a new class of bioresorbable protein scaffold. Although many factors influence the choice of surgical approach and the specific product used for soft tissue support and repair, the goal is to improve long-term outcomes while minimizing complications and recurrences requiring further revisional surgery. In this review, the basic science,  clinical characteristics, and clinical applications of SERI R Surgical Scaffold, a novel, engineered, highly purified product for soft tissue support and repair will be presented.

Keywords: abdominal wall reconstruction; breast revision; highly purified silk; SERI R Surgical Scaffold; soft tissue support

Introduction inconsistent thickness of autologous tissue can cre- ate challenges, including delayed wound healing and Much of what is done within the scope of recon- ischemic complications.3 In reality, there are limited structive and revision surgery is designed to restore, supplies of “expendable” tissues, and soft tissue rein- repair, rebuild, and support damaged, weakened, forcement needs may exceed donor site dimensions. or absent tissue. A variety of options for soft tis- Autologous dermal collagen or fascia grafts remain sue reinforcement currently exist, and more sur- an option to reinforce small defects. geons are utilizing these products in order to Surgeons have five main categories of nonau- achieve the best long-term outcome. A starting tologous, off-the-shelf options for soft tissue sup- point for understanding how the various soft tissue– port and repair (Table 1, Fig. 1). The mostly widely support options fit into the surgical armamentar- used of these are acellular dermal matrices (ADMs), ium begins with the basic science of biomechanical which are uniquely processed tissues derived from performance at time zero (i.e., implantation). How- human or animal sources. ADMs have been used ever, additional considerations are needed, includ- in a variety of procedures (e.g., burn injury resur- ing how the native tissue may interact with the facing, support, abdominal hernia implanted material and the risk of adverse events repair) and show promise for other aesthetic and over both the short and long terms. reconstructive purposes.4 However, their utility may Although adjunctive soft tissue support in be limited by size, strength, cost, and concerns primary procedures may decrease the risk of inad- regarding adverse events.5 Additional options for equate repair and ensuing deformities, the abil- soft tissue reinforcement include absorbable or per- ity of the human body to serve as its own donor manent synthetic mesh. Overall, these products source is countered by the risk of deformity are commonly used to provide additional support and loss of functionality at the donor site.1,2 In during breast reconstruction6–8 and during addition, the increased metabolic demands and

doi: 10.1111/nyas.12886

44 Ann. N.Y. Acad. Sci. 1358 (2015) 44–55 C 2015 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non.]commercial and no modifications or adaptations are made. Jewell et al. The development of SERI R Surgical Scaffold

Table 1. Examples of available products for soft tissue support and repair

Source Resorbable

Biological Silk matrix SERI R Surgical Scaffold (Allergan, Inc., Medford, MA)25 Silk Yesa Acellular dermal matrix NA Human AlloDerm R (LifeCell Corp., Branchburg, NJ)43 Human dermis AlloMaxTM (Davol, Inc., Warwick, RI)44 Human dermis DermaMatrixTM (Synthes, West Chester, PA)45 Human dermis FlexHD R (Musculoskeletal Transplant Foundation, Edison, Human dermis NJ)46 Repriza R (Specialty Surgical Products, Inc., Victor, MT)47 Human dermis Porcine StratticeTM (LifeCell Corp.)48 Porcine dermis XCM (Kensey Nash Corp., Exton, PA)49 Porcine dermis Bovine SurgiMend R (TEI Biosciences Inc., Boston, MA)50 Bovine dermis Veritas R (Synovis, St Paul, MN)51 Bovine pericardium Synthetic Absorbable VicrylTM (Ethicon, Somerville, NJ)52 Polyglactin (copolymer of Yes; NA glycolide and lactide) PHASIXTM (Davol Inc.)53 Poly-4-hydroxybutyrate Yes; 12–18 months TIGR R Matrix (Novus Scientific, San Diego, CA)54 Fiber 1: copolymer of glycolide, Yes; 4 months (fiber lactide, and trimethylene 1); 3 years (fiber 2) carbonate Fiber2:copolymeroflactideand trimethylene carbonate Permanent, nonresorbable ProleneTM (Ethicon)55 No Composite Partially resorbable ProceedTM (Ethicon)56 Polypropylene + cellulose + Yes; 4 weeks polydioxanone (cellulose); 6months (polydioxanone) UltraproTM (Ethicon)57 Polypropylene + poliglecaprone Yes; 84 days 25 ParietexTM (Covidien, New Haven, CT)58 + collagen Yes; 14 days Permanent, nonresorbable DUALMESH R (W.L. Gore & Associates, Inc., Flagstaff, AZ)59 Expanded No polytetrafluoroethylene aIn an ovine model, significant absorption was noted over 24 months (Data on file, Allergan, Inc.). NA, not applicable. abdominoplasty or repair of abdominal hernias;9–13 silk product for soft tissue support and repair, will however, if synthetic mesh becomes infected or be presented. SERI Surgical Scaffold is U.S. Food extrudes, there may be significant morbidity. and Drug Administration (FDA) 510(k) cleared In this review, the basic science, clinical char- for soft tissue reinforcement where deficiencies acteristics, and clinical applications of SERI R Sur- exist. Although there are many options for soft tis- gical Scaffold, a novel, engineered, highly purified sue reinforcement, a strong, pliable, bioresorbable

Ann. N.Y. Acad. Sci. 1358 (2015) 44–55 C 2015 The Authors. Annals of the New York Academy of Sciences 45 published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences. The development of SERI R Surgical Scaffold Jewell et al.

Autologous Nonautologous

Native tissue Biological Synthetic • Harvested from donor site • Derived from natural sources/materials • Derived from man-made materials of patient

SERI® Acellular Absorbable Permanent Composite Surgical dermal • May be nonresorbable • Barrier- • May be matrix composed of coated Scaffold polyglactin or composed of synthetic • Derived from • Derived from polyglycolic polypropylene mesh ultra-purified human or or silk animal tissue polyester

Human Porcine Bovine Partially Permanent resorbable nonresorbable (cadaver) • Derived from • Derived from • May be • May be dermal tissue dermal tissue • Derived from composed of composed of or small or dermal tissue polypropylene ePTFE intestine pericardium + cellulose or submucosa polyester + collagen

Figure 1. Classes of soft tissue support and repair devices. ePTFE, expanded polytetrafluoroethylene. productsuchasSERISurgicalScaffoldoffersa commercial size of the lot, quality testing deter- combination of attributes that have not been for- mines properties such as appearance, linear mass, merly encountered in soft tissue support and repair evenness, cleanliness, neatness, breaking tenacity, devices. elongation at break, and cohesion. SERI Surgical Scaffold is produced from the highest grade (and Engineering of SERI Surgical Scaffold therefore most consistent) silk available, sourced from the domesticated Bombyx mori silkworm. Source and composition of silk Native (raw) silk can be described in terms of its two Differentiation of SERI Surgical Scaffold from component structures: fibroin and sericin. Fibroin is surgical suture a pure protein with a –Gly–Ala–Gly–Ala–Gly–Ser– Sericin removal achieves several purposes. Native repeat along its sequence.14 Fibroin proteins form (raw) silk lacks the sheen and drape associated with a high-volume fraction of ␤-sheet microcrystallites sericin-depleted silk. Removal of the sericin makes that provide the majority of strength and stiffness the silk “silky” and renders it more easily dyeable, to silk.15 In contrast, sericin is a mixture of proteins which is typically necessary not only for textiles, and contains a large number of amino acids with but also for colored silk sutures. Visual differences hydroxyl groups (Ser, Thr, and Tyr). Sericin forms between native (raw) and purified silk fibers are the rough outer coating of native (raw) silk that shown in Figure 2. In addition, as the silk aller- functions as an adhesive to maintain the structural gens are found in the sericin layer,17 sericin removal integrity of the moth cocoon.15 Two fibroin strands reduces or eliminates the immunogenicity of silk (brins), surrounded by a layer of sericin, compose threads,18,19 which improves its biocompatibility.20 the native (raw) silk filament.15 Although sericin is loosened during the reeling pro- After harvesting, cocoons are placed in hot water cess, it is not completely removed. Various textile to loosen the sericin, allowing the silk filaments to technology–based sericin-removal processes exist, be reeled.16 Because silk is a natural fiber, there is involving water, heat, and a variety of surfactants some variability in the properties of native (raw) and salts, which achieve different degrees of sericin silk. During reeling, the size of the yarn is calculated removal. SERI Surgical Scaffold undergoes a pro- through electronic or mechanical sensors to deter- prietary sericin-removal process and subsequent mine fiber consistency. After reeling, the silk yarn is silk fibroin purification processes that result in an graded for weight and quality according to interna- ultra-pure fibroin strand. These proprietary pro- tional standards. Although weight determines the cesses conform to medical industry guidance and

46 Ann. N.Y. Acad. Sci. 1358 (2015) 44–55 C 2015 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences. Jewell et al. The development of SERI R Surgical Scaffold

Figure 2. Representative images of (A) raw and (B) purified silk fibers. effectively remove the immunogenic sericin coating Surgical Scaffold manufacturing process results in from the native (raw) silk (data on file, Allergan, a product with a highly consistent structure as well Inc.). The highly purified silk fibroins that make as consistent physical and mechanical properties up SERI Surgical Scaffold are not dyed or coated (dataonfile,Allergan,Inc.;Table2).Assuch,SERI with wax. SERI Surgical Scaffold is manufactured Surgical Scaffold has predictable elongation and in compliance with ISO 13485 quality standard and dimensional stability characteristics under clinically FDA quality system regulations 21CFR820 to ensure relevant biomechanical loading. In its hydrated its reproducibility. state, SERI Surgical Scaffold provides approxi- ThepropertiesofSERISurgicalScaffoldarein mately 7% elongation in the transverse direction contrast to those of surgical silk sutures, which are and approximately 4% elongation in the vertical highly reactive in their native form21 and continue direction with an applied force of 16 N (data on file, to elicit a strong inflammatory reaction as braided Allergan, Inc.). In addition, SERI Surgical Scaffold silk suture.22,23 In addition, processed silk sutures are typically coated with wax or silicone to prevent Table 2. Physical and mechanical properties of SERI Sur- fraying,21 and have been associated with inflamma- gical Scaffold tion and formation.24 Data Textile technology and resulting material properties of SERI Surgical Scaffold Lot No. Lot No. Properties Specification P2010082601 P2010102001 SERI Surgical Scaffold is indicated “for use as a tran- sitory scaffold for soft tissue support and repair to Dimensions 10 × 25 10 × 26 10 × 25 reinforce deficiencies where weakness or voids exist (cm) that require the addition of material to obtain the Thickness 0.6–1.0 0.9 0.9 desired surgical outcome. This includes reinforce- (mm) > × 6 × 6 ment of soft tissue in plastic and reconstructive Pore area 10,000 1.36 10 1.31 10 ␮ 2 surgery, and general soft tissue reconstruction.”25 To ( m ) Burst strength 0.54–1.27 0.68 0.71 achieve this end, ultra-purified silk yarns are knitted (MPa) using a proprietary design to create a tear-resistant Burst stiffness 30–50 40 40 mesh that can be cut in any direction without unrav- (N/mm) eling and with excellent suture retention requiring Fibroin purity ࣙ95 96a 96b only a 3-mm suture bite (data on file, Allergan, Inc.; (%) Fig. 3). Shelf-life 36 All parameters within specs at After knitting, SERI Surgical Scaffold is subjected (months) 36 months to two additional proprietary purification pro- aYarn Lot No. E2010071902. cesses that cleanse the product. Overall, the SERI bYarn Lot No. E2010092701.

Ann. N.Y. Acad. Sci. 1358 (2015) 44–55 C 2015 The Authors. Annals of the New York Academy of Sciences 47 published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences. The development of SERI R Surgical Scaffold Jewell et al.

Figure 3. Representative images of SERI Surgical Scaffold demonstrating (A) its knit pattern and (B) cutting without unraveling. does not have an orientation surface, which is in the SERI Surgical Scaffold (data on file, Allergan, contrast to some soft tissue support products. SERI Inc.; Fig. 5). Furthermore, integration of SERI Sur- Surgical Scaffold is terminally sterilized with an gical Scaffold into the surrounding tissue resulted ethylene oxide process. The final product is a sterile, in minimal inflammation, consistent with a normal knitted, multifilament, long-term bioresorbable wound-healing response. scaffold. The application of customizable textile SERI Surgical Scaffold was subsequently eval- technology processes from yarn to fabric design—in uated in an ovine model of two-stage breast combination with unique purification processes— reconstruction.7 In this model, a tissue expander was establishes SERI Surgical Scaffold as a novel device implanted to gradually enlarge the space beneath for soft tissue reinforcement. Future iterations of the latissimus dorsi muscle and the overlaying fas- SERI Surgical Scaffold can be developed with cus- cia to accommodate a breast implant. SERI Surgical tomized physical, mechanical, and bioresorption Scaffold was sutured between the latissimus dorsi properties for specific soft tissue support and repair muscle and chest wall to bridge and mechanically applications. reinforce the void created by the tissue expander. In this study, SERI Surgical Scaffold was shown to Basic science of SERI Surgical Scaffold provide support to the lower pole of the reconstruc- In vitro cell culture was used to evaluate the attach- tion pocket; no excessive tissue expander mobil- ment and proliferation of human dermal fibroblast ity (i.e., ࣙ4 cm) was noted during the exchange cells on SERI Surgical Scaffold. In this study, cells procedure conducted at 3 months and no tissue were directly seeded at a concentration of 2 × 106 expander/breast implant migration was noted at cells/mL onto SERI Surgical Scaffold, and scanning the time of necropsy.7 The thickness of the SERI electron microscopy was performed after 1, 7, and Surgical Scaffold plus integrated tissue (generated 14 days of incubation. Representative images from deep to the panniculus carnosus muscle and lateral day 14 postseeding are shown in Figure 4 (data on to the breast implant) was measured at the time file, Allergan, Inc.). of necropsy with a thickness gauge. At 3 months, Initial preclinical studies to evaluate the histo- the mean thickness of SERI Surgical Scaffold plus logic and immunologic responses to SERI Surgi- integrated tissue was 2.5 ± 0.9 mm (relative to cal Scaffold utilized a rat abdominal wall defect 0.9 ± 0.0 mm at baseline (i.e., implantation)).7 model, which had previously been used to eval- However, there was no significant difference in the uate VicrylTM mesh.26 In this animal model, mean thickness of SERI Surgical Scaffold plus inte- neovascularization was observed morphologically grated tissue from the 3-month assessment through as early as 2 days postimplantation and was con- the final 12-month assessment.7 In addition, vas- firmed by positive staining for smooth muscle actin. cularization of the ingrown tissue was evident by By 28 days postimplantation, tissue ingrowth and the first assessment conducted at the 1-month blood vessels were observed around the fibers of necropsy.7

48 Ann. N.Y. Acad. Sci. 1358 (2015) 44–55 C 2015 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences. Jewell et al. The development of SERI R Surgical Scaffold

Figure 4. Representative images of cell attachment to SERI Surgical Scaffold. Images captured by scanning electron microscopy at 500x magnification on day 14 after seeding with (A) human dermal fibroblast cells or (B) media only (negative control).

In this preclinical study, the strength of SERI Sur- strength at the implant site (consisting of SERI Sur- gical Scaffold was also measured using a standard gical Scaffold plus ingrown tissue) was determined ball-burst method (data on file, Allergan, Inc.), by using collagenase to digest the ingrown tissue which allows calculation of the amount of force a before burst testing.7 The resulting burst strength tissue sample can withstand before rupturing. The was therefore due to SERI Surgical Scaffold. The contribution of SERI Surgical Scaffold to the overall collagenase-processed SERI Surgical Scaffold

Figure 5. Representative trichrome image of SERI Surgical Scaffold and associated histologic response in a rat abdominal wall defect model. Image captured at 4x magnification on day 28 after implantation of SERI Surgical Scaffold.

Ann. N.Y. Acad. Sci. 1358 (2015) 44–55 C 2015 The Authors. Annals of the New York Academy of Sciences 49 published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences. The development of SERI R Surgical Scaffold Jewell et al.

350

300

250

200

y = 6.1766In(x) + 185.36 150

100 Ultimate burst load (N) Avg. ovine fascia ultimate burst load (baseline)

50 y = –25.39In(x) + 65.723

0 0 3 6 9 12 Soft tissue support in-life duration (months)

Sham capsule tissue Collagenase-processed SERI Surgical Scaffold

SERI Surgical Scaffold + tissue Native tissue strength Figure 6. Transfer of load-bearing responsibility from SERI Surgical Scaffold to native tissue over time. Reproduced from Ref. 7 with permission. progressively lost strength and structural integrity Surgical Scaffold implanted to support a breast over time such that the final measurement could implant; these results are expected in 2015. In addi- not be taken at 12 months.7 However, burst strength tion, SERI Surgical Scaffold has been evaluated in was maintained throughout the 12 months of the several clinical studies. study for the SERI Surgical Scaffold plus ingrown Clinical studies with SERI Surgical tissue samples.7 In combination, these results Scaffold support a transfer of the load-bearing responsibility from SERI Surgical Scaffold to the newly generated The SURE (SERI Use in Reconstruction)-001 and native tissue over time (Fig. 6).7 In addition, nearly SURE-002 clinical studies were designed to evaluate complete bioresorption of SERI Surgical Scaffold outcomes in women undergoing breast reconstruc- was evident by 12 months based on histological tion following mastectomy. SURE-001 was a 2-year, assessment (Fig. 7).7 Minimal inflammation prospective, multicenter clinical study evaluating was observed with no evidence of granuloma two-stage breast reconstruction using SERI Surgical formation.7 Primary cell types associated with Scaffold during tissue expander placement in stage SERI Surgical Scaffold were macrophages and 1 surgery, followed by breast implant exchange multinucleated giant cells.7 A uniform distribution during stage 2 surgery (ClinicalTrials.gov iden- of collagen types I and III was apparent by 1 month tifier: NCT01256502). Published results through with type I collagen predominant by 12 months.7 12 months demonstrated high marks by surgeons An additional preclinical study utilized the for both satisfaction and ease of use of SERI Surgical ovine model of two-stage breast reconstruction to Scaffold.27 At month 12, the mean satisfaction score evaluate the effect of ionizing radiation on SERI was 9.4 (wherein 10 was considered “very satisfied”)

50 Ann. N.Y. Acad. Sci. 1358 (2015) 44–55 C 2015 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences. Jewell et al. The development of SERI R Surgical Scaffold

Figure 7. Representative trichrome images of SERI Surgical Scaffold and associated histologic response in an ovine model of two-stage breast reconstruction. Reproduced from Ref. 7 with permission.

and SERI Surgical Scaffold was considered “easy during subpectoral placement of a permanent orveryeasy”touseinࣙ8% of cases (evaluated breast implant (ClinicalTrials.gov identifier: across five categories during stage 1 surgery (i.e., NCT01389232). Outcome measures were similar to before, during, and after implantation)).27 Ahigh those for the SURE-001 clinical study, and included level of patient satisfaction with their breasts surgeon satisfaction, ease of use of SERI Surgical was also reported in this study (mean score 4.5 Scaffold, patient satisfaction with their breasts, and at month 12 (wherein 5 was considered “very adverse event rates. Data from the SURE-002 clinical satisfied”)).27 Adverse event rates were low through study are expected in 2015 and will be reported. 12 months: tissue necrosis, seroma, hematoma, Biologic response to SERI Surgical implant loss, capsular contracture, and breast Scaffold occurred in 6.7%, 5.7%, 4.8%, 3.8%, 1.9%, and 1.0% of breasts, respectively.27 Tissue The biologic response to all implanted foreign mate- samples collected during stage 2 surgery for his- rials of any origin occurs with some predictability tology were read as normal for 68/69 samples, and but also some variability, according to the source of showed resorption of SERI Surgical Scaffold and the material or implant.28 Incorporation of biolog- tissue ingrowth with vascularization.27 One tissue ical components of allogeneic or xenogeneic origin sample was rated as abnormal (in a patient who has specific challenges, as the foreign body reaction experienced a hematoma requiring evacuation), to implanted material may affect the compatibil- which was attributed to lack of tissue integration ity/safety and performance of .28 The and bioresorption of the SERI Surgical Scaffold.27 ideal would produce a predictable and SURE-002 was a 2-year, prospective, multi- minimal inflammatory response and tissue gen- center clinical study evaluating direct-to-implant eration and would eventually be bioresorbed and breast reconstruction using SERI Surgical Scaffold Bioreplaced.

Ann. N.Y. Acad. Sci. 1358 (2015) 44–55 C 2015 The Authors. Annals of the New York Academy of Sciences 51 published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences. The development of SERI R Surgical Scaffold Jewell et al.

The biologic response to SERI Surgical Scaf- minimal neovascularization was noted at 20 weeks fold appears similar across the various human and while rates of tissue ingrowth and tensile strength animal models studied. Tissue response is pre- differed between ADM sources.35 In addition, a mix- dictable and generally mild, with macrophages ini- ture of mature and immature collagen was noted tially appearing followed by generation of type III over the 20-week study.35 Combined, these results and ultimately type I collagen.7 Some macrophages indicate an improved tissue response to meshes are observed to fuse together, forming multinucle- resorbed over the long term, but highlight the need ated giant cells,7 which have been associated with for studies that more clearly document the time degradation of silk.21 course of tissue response and neovascularization withvariousmeshtypes. Biologic response to other materials Clinical applications of SERI Surgical Studies of other soft tissue support devices indi- Scaffold cate a tissue response dependent on production of scar tissue from chronic inflammation (as seen with SERI Surgical Scaffold has many characteristics synthetic mesh)29 or on revascularization of a highly that may provide an advantage over products that processed collagen matrix from human-derived tis- have an entire or partial synthetic construct, are sue (as seen with ADMs), which occurs over a period derived from human or animal tissues, or are of weeks to months. In a study of Vicryl compared quickly hydrolyzed by the body (e.g., polyglactin). with Prolene R (Ethicon) and UltraproTM (Ethicon), For instance, the ultra-pure strands of fibroin in Vicryl was found to provoke a stronger angiogenic SERI Surgical Scaffold prompt a muted immune and inflammatory response resulting in significantly response.7 SERI Surgical Scaffold is a moldable, dra- reduced strength due to hydrolytic breakdown of pable, and easy-to-cut template for use in a variety the device.30 Moreover, the tissue surrounding the of procedures. The ease of use of SERI Surgical Scaf- Vicryl mesh was unstable due to low collagen fold is reflected by high surgeon satisfaction scores content and massive inflammatory cell infiltra- for its performance in the operating theater.27,36 The tion, resulting in poor incorporation into the host perforations permit fluid egress, which may lead to tissue.30 Another study reported that polypropylene a clinical reduction in drain output and potentially mesh was associated with persistent chronic inflam- low seroma rates with SERI Surgical Scaffold. The mation, with foreign-body granulomas surround- perforations also allow easy placement of sutures ing the fibers and collagen essentially encapsulating through the interstices and permit visualization of the mesh at 3 years.31 In this study, TIGR R Matrix underlying vital structures or devices (Fig. S1). The (Novus Scientific) was associated with a medium- surface texture of SERI Surgical Scaffold, which term inflammatory response that decreased by becomes rough and “grippy” following placement, year 2, and a collagen layer within and surround- helps the scaffold bind tissues together (Fig. S2). ing the mesh by 2 years.31 Similarly,areportof Functionally, SERI Surgical Scaffold has been shown PHASIX mesh (poly-4-hydroxybutyrate (P4HB); to have nearly two times the strength of native ovine Davol Inc.) reported mild inflammation at 26 and fascia at inset (Data on file, Allergan, Inc.). As SERI 52 weeks, with slightly detectable macrophages, Surgical Scaffold is bioresorbed, it is replaced with barely detectable giant cells, and mild-to-moderate a collagen matrix that maintains the initial strength granulation tissue/revascularization.32 While neo- of the scaffold.7 Despite its strength, SERI Surgical vascularization was reported by the first assessment Scaffold remains pliable (Fig. S3), typically two very at 4 months with TIGR Matrix,31 mild-to-moderate distant qualities of soft tissue repair devices. evidence of vascularization was observed by the first Complications remain a problem in surgery of assessment at 6 weeks with P4HB as a mesh or the breast and abdomen. In abdominal surgery, plug.32 reoperations to repair incisional hernias have been Comparative studies of ADMs report differing reported for 63% and 32% of patients with suture biologic responses, ranging from mild-to-severe versus mesh repairs, respectively.37 Revision rates inflammation33 and scaffold remodeling to fibrous as high as 25% have been reported in postmar- encapsulation.34 In one study comparing vari- keting studies evaluating breast implants,38,39 with ous human- and animal (porcine)-derived ADMs, higher rates typically associated with a prior revision

52 Ann. N.Y. Acad. Sci. 1358 (2015) 44–55 C 2015 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences. Jewell et al. The development of SERI R Surgical Scaffold or in complex reconstruction procedures.38,39 The PhD, and Karen Stauffer, PhD, of Evidence Scientific most common drivers of revision in the breast Solutions, which was funded by Allergan, Inc. include ptosis, capsular contracture, and lower pole Conflicts of interest deformities.40 The characteristics and clinical qual- ities of SERI Surgical Scaffold are well suited to Mark Jewell is an approved clinical investigator and support weak tissues and to reinforce repairs, ren- consultant for Allergan, Inc. William Daunch is a dering SERI Surgical Scaffold potentially valuable current employee of Allergan, Inc. Bradley Bengt- for a variety of procedures. son is an approved clinical investigator and a consul- A recent survey reported high surgeon satisfac- tant for Allergan, Inc. and LifeCell/Acelity. Enrico tion with the clinical outcomes associated with the Mortarino is a former employee of Allergan, Inc. use of SERI Surgical Scaffold in diverse procedures requiring soft tissue support and repair.36 In addi- Supporting Information tion, a published case report demonstrated favor- Additional supporting information may be found able results with SERI Surgical Scaffold when used in the online version of this article. prophylactically to support a circumferential body lift in a patient with massive weight loss.41 Publica- Figure S1. (a) SERI Surgical Scaffold is inset with tion of additional data from postmarketing studies, absorbable polydioxanone monofilament suture. case studies,42 and retrospective reviews of available (b) SERI Surgical Scaffold is used to provide soft data13 will help further characterize the role for SERI tissue support for a reduction mammoplasty. It is Surgical Scaffold in clinical practice. inset with a combination of interrupted and contin- uous barbed monofilament absorbable sutures. Conclusions Figure S2. This is an application of soft tissue sup- port with SERI Surgical Scaffold to reinforce the SERI Surgical Scaffold presents a uniquely engi- inferior pedicle of a reduction mammoplasty and neered product to provide soft tissue support where prevent dropout. weakness exists and where native tissues would ben- efit from additional support. Its ease of cutting Figure S3. SERI Surgical Scaffold tissue incorpora- and shaping to suit individual needs lends it to tion over time. Initially, SERI Surgical Scaffold bears innovative uses. Studies have demonstrated early most of the soft tissue load and is replaced with neovascularization and gradual bioresorption of type 1 collagen over time. Note the suppleness of SERI Surgical Scaffold over time, allowing transfer the SERI–collagen construct. of function back to the body’s own generated tis- sues without sacrifice of strength and with minimal complications. Although a multitude of soft tissue References support products have come to market over the last 1. Atisha, D. & A.K. Alderman. 2009. A systematic review of decade, many have potential limitations owing to abdominal wall function following abdominal flaps for post- cost, permanency, limited size/shelf life, or recurrent mastectomy breast reconstruction. Ann. Plast. Surg. 63: 222– complications, such as stretch deformity and lack of 230. maintenance of the surgical outcome. SERI Surgical 2.Zhong,T.,C.McCarthy,S.Min,et al. 2012. Patient sat- Scaffold has the potential to circumvent many of the isfaction and health-related quality of life after autologous tissue breast reconstruction: a prospective analysis of early issues that accompany human- or animal-derived postoperative outcomes. Cancer 118: 1701–1709. tissues and synthetic meshes while providing sur- 3. Serletti, J.M., J. Fosnot, J.A. Nelson, et al. 2011. Breast recon- geons a predictable, long-term, bioresorbable, and struction after breast cancer. Plast. Reconstr. Surg. 127: 124e– bioreplacable option for patients in need of soft tis- 135e. sue support. 4. Macadam, S.A. & P.A.Lennox. 2012. Acellular dermal matri- ces: use in reconstructive and aesthetic breast surgery. Can. J. Plast. Surg. 20: 75–89. Acknowledgments 5. Smart, N.J., N. Bryan, J.A. Hunt & I.R. Daniels. 2014. Porcine dermis implants in soft-tissue reconstruction: current status. The authors thank Kristen Biber for her contribu- Biologics 8: 83–90. tion to the development of this manuscript. Med- 6. Colwell, A.S., O. Tessler, A.M. Lin, et al. 2014. Breast ical writing support was provided by Lynne Isbell, reconstruction following nipple-sparing mastectomy: pre-

Ann. N.Y. Acad. Sci. 1358 (2015) 44–55 C 2015 The Authors. Annals of the New York Academy of Sciences 53 published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences. The development of SERI R Surgical Scaffold Jewell et al.

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Ann. N.Y. Acad. Sci. 1358 (2015) 44–55 C 2015 The Authors. Annals of the New York Academy of Sciences 55 published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.