Scaffold Material with a Self-Stabilizing Structure

Europaisches Patentamt ||||||| |||||| ||| ||||| ||||| ||||| ||||| ||||| ||||| ||||| ||||| |||||| |||| |||| ||| (1 9) Qjl) European Patent Office

Office euroDeen des brevets (11) EP 0 963 834 A1

(12) EUROPEAN PATENT APPLICATION

(43) Date of publication: (51) int. CI.6: B29C 67/00, B22C 7/02, 15.12.1999 Bulletin 1999/50 E04G 1/00, A61 L 27/00, (21) Application number: 98304496.7 D04H 1 3/00, B01 D 39/1 4

(22) Date of filing: 08.06.1998

(84) Designated Contracting States: (72) Inventor: Ingber, Donald E. AT BE CH CY DE DK ES Fl FR GB GR IE IT LI LU Boston, Massachusetts 021 1 6 (US) MCNLPTSE Designated Extension States: (74) Representative: AL LT LV MK RO SI Greenwood, John David et al Graham Watt & Co. (71) Applicant: Riverhead Molecular Geodesies, Inc. Sevenoaks Kent TN13 2BN (GB) Boston, Massachusetts 02199 (US)

(54) Scaffold material with a self-stabilizing structure

(57) A scaffold material is provided which comprises a predetermined arrangement of integrally connected modules, each said module comprised of a plurality of integrally connected elongated members forming at least a portion of a polyhedron, the members arranged such that at least a portion of said members form geodesic or tensegrity elements. The scaffold material can be used in various ways, such as in filtration material, catalysis, protective textile fabrics, production of patterns for making moulds by shell investment casting, and biomedical applications, e.g. detoxification.

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Description vide a material having novel mechanical and bioactive properties. It is a further object of the invention to pro- Field of the Invention vide a material useful as a protective shield or textile and for filtration, detoxification and biomedical applica- [0001] This invention relates to three-dimensional 5 tions. structures which possess geodesic features and can [0006] The present invention describes three-dimen- stabilize through use of tensegrity. sional biomimetic scaffold materials which possess geodesic features, can stabilize through use of tenseg- Background of the Invention rity and may be fabricated as unitary structures on the 10 micro or macro scale. [0002] There is a need to develop new light-weight, [0007] In one aspect of the invention, a scaffold mate- porous materials that exhibit enhanced mechanical rial is provided which possesses a predetermined strength, flexibility and exposed surface as scaffolds for arrangement of integrally connected modules, each detoxification, filtration, catalysis, textile fabrics, space- said module comprised of a plurality of integrally con- filling, space-covering and biomedical applications. The 15 nected elongated members forming at least a portion of ultimate material would be biomimetic materials that a polyhedron, the members arranged such that at least mimic the mechanical responsiveness and bioprocess- a portion of said members form geodesic or tensegrity ing capacities of living cells and tissues. elements. [0003] Living cells and tissues use tensegrity architec- [0008] By "scaffold," as that term is used herein, it is ture to organize and mechanically stabilize their internal 20 meant a material having an extended repeating struc- filamentous support networks (interconnected nuclear ture, which forms a framework or skeleton onto which matrix, cytoskeletal, and extracellular matrix scaffolds) and into which additional components may be intro- and hence, their three dimensional forms (see, J. Cell duced to impart additional features to the material. Sci. 104:613,1993). The concept of tensegrity is well- [0009] By "module," as that term is used herein, it is known in the fabrication of geodesic structures, such as 25 meant a plurality of integrally connected structural geodesic domes. See, for example, U.S. Patent Nos. members that delineate the edges of at least a portion 3,063,521, 3,354,591 and 4,901,483. Tensegrity con- of a polyhedron. struction is based upon the realization that most build- [001 0] By "integrally connected," as that term is used ing materials are much more efficiently utilized and can herein, it is meant a single composition or structure often withstand higher forces when in tension than 30 made up of a plurality of elements to form a single uni- when in compression. In tensegrity construction, there tary body. The structure does not posses discrete con- is a high ratio of tension to compression elements. The nectors or additional bonding or adhesive materials. tension members in these structures are geodesic ele- [0011] By "geodesic element," as that term is used ments that delineate the shortest distance between ver- herein, it is meant a geometric element which defines tices that define an enclosed polyhedron. The 35 the shortest distance between two points on the surface mathematical modeling rules for the building and of a solid. For example, a line is the shortest distance designing of tensegrity structures is also well under- between two vertices on a surface of a polyhedron, a stood. See, for example, Kenner in Geodesic Math path along a great circle is the shortest distance (and (1980) in which the basic mathematics defining the ori- hence, a geodesic element) for a sphere, and a spiral is entation of individual structural elements within simple 40 a geodesic element on the surface of a cylinder. A trian- tensegrity modules is described. These models have gle is geodesic because it represents the shortest, most been directed to macrostructures suitable for use in economical path between three vertices on the surface large-scale objects, such as buildings and toys. See, of a polyhedron. U.S. Patent No. 3,695,617. These macrostructures have [0012] By "tensegrity element," as that term is used been prepared by joining individual elements in the 45 herein, it is meant an arrangement of interconnected desired three dimensional arrangement and hence are structural members that self-stabilizes through trans- not well suited to miniaturization. mission of continuous tension and discontinuous com- [0004] Thus, there remains a need to prepare materi- pression. Tensegrity elements may be composed of als which can exhibit the mechanical responsiveness members that selectively resist tension or compression and bioprocessing capabilities of living cells and tis- so locally or of all non-compressible members that may sues. This invention is based on recent advances that resist either tension or compression depending on their have been made in our understanding of the relation location and the path of force transmission. A triangle between microstructure and macroscopic behavior in composed of all non-compressible struts is an example living cells and tissues. of the latter type of self-stabilizing tensegrity structure. 55 [0013] By "extensible element," as that term is used Summary of the Invention herein, it is meant an element that is capable of extension or an increase in the length of the member within a [0005] It is an object of the present invention to pro- given range of movement in response to application of a

2 3 EP 0 963 834 A1 4 tensile force to one or both ends of the member. closed octahedral tensegrity structure that exhibits [001 4] By "non-compressible element," as that term is a "dog-leg" geometry; used herein, it is meant an element that is incapable of Figure 8 is a computer simulation illustrating a shortening along its length when compressive forces series of dynamic geometric transformations within are applied to one or both ends of the member. How- s three cuboctahedron modules that are joined along ever, the non-compressible member may be able to a common triangular face, which is capable of rear- buckle under compression, without shortening its ranging from a linear, flexible cuboctahedral array to length. A non-compressible member may or may not be form a nonlinear, rigid, closed octahedral tensegrity able to extend in length when external tensile forces are arrangement different than that shown for Fig. 6; applied to its ends. Such an extensible, non-compressi- 10 Figure 9 is an illustration of a scaffold material ble member would be able to withstand compression, coated with a hydrogel (Fig. 9a) and impregnated but not tension. with an additional detoxification agent (Fig. 9b); Figure 10 is a computer simulation illustrating that Brief Description of the Drawing the addition of larger fibers that are stiff, yet flexible, 15 to a modular network results in the increased resist- [0015] The present invention is described with refer- ance to distortion and a tensegrity network that stiff- ence to the following Figures, which are presented for ens and is held open when stressed; the purposes of illustration only and which are by no Figure 11 is an illustration of a geodesic material means intended to be limiting of the invention and in composed of all extensible members arranged into which: 20 a spherical module; Figure 12 is an illustration of two cuboctahedron in Figure 1 is an illustration of a cuboctahedron mod- different stages of contraction and rearrangement ule containing non-compressible elongated mem- which demonstrates that the individual modules are bers which can rearrange to self-stabilize through not required to behave in a concerted fashion; and tensegrity; 25 Figure 13 is an illustration of a computer model of Figure 2(a) illustrates a hierarchical, nucleated the deformation of two linked cuboctohedra (Fig. tensegrity "cell" model composed of sticks and 13a and 13b), and of the corresponding deforma- strings and Figure 2(b) illustrates the coordinated tion of two linked cuboctohedra fabricated by spreading of the cell and nucleus that occurs when CAD/CAM methods (Fig. 13c and 13d). living cells adhere to an adhesive substrate; 30 Figure 3 is a plot of mechanical stiffness (ratio of Detailed Description of the Invention stress to strain) v. applied stress for living cells (Fig. 3a) and for a tensegrity model (Fig. 3b); [001 6] The present invention applies the rules of bio- Figure 4 is an illustration of a fully geodesic scaffold logical cell and tissue organization as well as novel fea- material of the present invention using non-com- 35 tures of cellular biochemistry to the design and pressible elongated members and tetrahedron fabrication of synthetic materials with mechanical, modules; structural and chemical processing abilities similar to Figure 5 is an illustration of a flexible geodesic scaf- those of living tissues and cells. fold material composed of cuboctahedron modules [0017] The stability of most man-made structures impregnated with a swellable polymer before swell- 40 requires that compressive forces, caused by the pull of ing (Fig. 5a) and after swelling localized hydrogel gravity, be transmitted continuously across all key sup- islands (Fig. 5b) so that the scaffold material is pre- porting elements, a stone arch being a simple example. stressed and stiffened while retaining open pores; In contrast, tensegrity structural stabilization occurs Figure 6 is a computer simulation illustrating a when the structural members are arranged geodesically series of dynamic geometric transformations within 45 such that only a subset of isolated struts bear compres- an integrally connected scaffold composed of three sion and, instead, tension is continuous. In engineering cuboctahedron modules that are joined along a sin- terms, it describes a building system that self-stabilizes gle edge, which is capable of rearranging from a lin- through inclusion of isolated compression struts that ear, flexible cuboctahedral array containing a large place surrounding structural elements under tension or common central pore to form a linear, rigid, closed so that resist the inward-directed pull of surrounding con- octahedral tensegrity arrangement lacking any tractile or shrinkable tensile networks and thereby pore; impose a prestress in the entire structure. The simplest Figure 7 is a computer simulation illustrating a tensegrity unit therefore might be viewed as a tensile series of dynamic geometric transformations within string pulling against a single incompressible linear three cuboctahedron modules that are joined along 55 strut, e.g., a bow and bowstring. The prestress would be a different single edge than that shown in Fig. 6, the internal tension that is equilibrated in the system which is capable of rearranging from a linear, flexi- prior to force application. Tensegrity modules may be ble cuboctahedral array to form a nonlinear, rigid, organized together using similar building rules to create

3 5 EP 0 963 83434 A1 6 polyhedral modules that self-stabilize through tensegrity ics). This linear increase in stiffness in response to and their geodesic arrangement. By interconnecting applied stress is also a fundamental property of living multiple individual geodesic modules using similar cells and tissues. building rules, higher order hierarchical structures may [0022] The novel material disclosed herein is based be assembled. 5 upon the discovery that architectural principles that gov- [0018] In all tensegrity structures, a local applied ern the microstructure of biological elements play a role stress results in long-range transfer of tensile forces. in the responsiveness of living cells and tissues. The When all structural members are non-compressible and present invention applies these architectural principles all are arranged geodesically, as in a geodesic dome or to the fabrication of synthetic materials which mimic the octet truss, the entire structure is mechanically stable 10 mechanical, structural and chemical properties of living and exhibits enhanced mechanical load-bearing capa- tissue. bilities. [0023] It has been demonstrated that living cells use [001 9] When structural members are extensible, the tensegrity architecture to organize their cytoskeleton entire structure will distend while maintaining an overall and to stabilize themselves against shape distortion. shape (e.g., remaining a sphere at all levels of disten- is See, J. Cell Sci. supra, and J. Theor Bio. 181:125 sion) and will geodesically rearrange in response to an (1996), herein incorporated in their entirety by refer- applied stress. This structure will not self-stabilize ence. This type of building system self-stabilizes by except when the distending stress is released and incorporating isolated compression elements (e.g., allowed to contract and some or all of its extensible molecular struts, localized swelling pressures) that members have reached a non-compressible, compres- 20 place the surrounding network under tension and sion-resistant configuration. An example of such a thereby impose a prestress in the entire structure. structure is shown in Fig. 1 1 , in which the scaffold mate- These structures undergo global structural rearrange- rial is comprised of a plurality of geodesic integrally con- ments and geometric transformations when external nected extensible modules. The structure will change stress is applied locally (Figs. 2(a) and 2(b)). Tensegrity size or degree of extension when external stress is 25 networks containing flexible joints also are able to applied while maintaining the pattern of intermember undergo extensive geometric transformation even when relationships constant. Multiple dome modules such as the individual support struts are inflexible (Fig. 1). The shown in Fig. 1 1 may be integrally connected by a pla- most familiar examples of tensegrity architecture are the nar arrangement of geodesic elements, e.g., triangles of geodesic domes of Buckminster Fuller and the muscu- similar structural members. 30 loskeletal framework of man. In fact, the enhanced load- [0020] When all structural members are non-com- bearing capabilities of all geodesic structures (domes, pressible and only a subset of members are arranged octet trusses, etc.) are due to a tensegrity-based mech- geodesically, the stable geodesic triangulated elements anism of stress transmission and self-stabilization. can kinematically rearrange in response to applied [0024] Another feature of tensegrity structures is that stress by changing the angle between members of adja- 35 their mechanical stiffness increases in direct proportion cent geodesic elements at each vertex until all of the as the level of applied stress is raised (Fig. 3b). This is members reorganize to form a fully geodesic polyhedral a fundamental property of all living cells (Fig. 3a) and module, such as an octahedron or tetrahedron. The tissues, including human skin, and is responsible for entire structure then again becomes mechanically sta- their characteristic tensile strength and mechanical flex- ble and exhibits high mechanical strength. Fig. 1 dem- 40 ibility. In another feature of cellular structure, much of onstrates the dynamic structural transformations cellular metabolism functions in a solid state when possible in the three dimensional cuboctahedron mod- immobilized on the insoluble cytoskeleton of the cell. ule. The cuboctahedron module has four triangles Thus, mechanically-induced changes in cytoskeletal around each square opening. The transformation structure and mechanics will affect the behavior of bio- between a flexible polyhedral network and stiff octahe- 45 chemical processing molecules that associate with the dral and tetrahedral forms results from inward pulling cytoskeleton. Where the biologically-active species is and twisting. This model predicts structural transforma- load-bearing, such as cytoskeletal filaments and associ- tions that are observed in the actin skeleton of living ated bioactive molecules including enzymes, then the cells at the cellular level and within the lung alveoli at the mere change in cytoskeletal structure (and hence dis- tissue level. See, D. Ingber J. Cell Sci. 104:613 (1993). so tortion of these molecules) may induce changes in [0021 ] When only the tensile members are extensible chemical potential and thermodynamic states in the or when all members are non-extensible, but the com- system. See, D. Ingber, "Tensegrity: The Architectural pression struts are non-compressible or bucWeable, a Basis of Cellular Mechanotransduction," Annu. Rev. local applied stress will result in global structural rear- Physiol. 59: 575-599 (1997). rangements and a proportional or linear increase in the 55 [0025] According to the present invention, the scaffold mechanical stiffness of the entire structure as the level biomimetic material comprises a predetermined of applied stress is raised (Wang et al, 1993 Science; arrangement of integrally connected modules. Each Stamenovic etal., 1996 J. Theor. Biol; Fuller synerget- module is comprised of a plurality of integrally con-

4 7 EP 0 963 834 A1 8 nected elongated members which form at least a por- [0029] Each of the modules is integrally connected to tion of a polyhedron. The elongated members are its neighboring modules so as to form the scaffold mate- arranged such that at least a portion of the members rial. A scaffold forms a framework or internal skeleton form geodesic or tensegrity elements. Because the upon which or into which additional materials may be scaffold material encompasses geodesic and/or 5 introduced. tensegrity elements, the material exhibits superior [0030] The elongated members, modules and hence mechanical strength and responsiveness. A typical the scaffold material itself may be prepared from any scaffold material is shown in Fig. 4 as an octet truss suitable material, dependent upon the desired applica- possessing non-compressible elongated elements hav- tion. For example, the scaffold may be prepared from ing an open structure and repeating geodesic geometry, w non-erodible polymers such as, by way of example only, [0026] The modules may be any geodesically deline- polyacrylates, epoxides, polyesters, polyurethanes, ated polyhedral structure or portion thereof. The module poly(methacrylate), polyimides, and polysiloxanes. may be a fully geodesic polyhedron, such as a tetrahe- Where flexibility is desired, such as where the structural dron, or a more complicated omni-triangulated system, members are extensible, the elongated members may such as icosahedron (twenty sided polyhedron) a octa- 15 be prepared using an elastomer. The materials selec- hedron (eight sided polyhedron). Alternatively, the mod- tion of the elongated elements may be in part dictated ule may also contain non-triangular surface elements, by the method of manufacture and by the intended such as square, pentagonal, hexagonal or octagonal application, which are discussed hereinbelow. facets. In other alternative embodiments, the module [0031 ] The elongated members are of a dimension may be a more complicated polyhedron which itself can 20 dictated by the intended application of the resultant be further decomposed into simpler geodesic elements. scaffold material. However, the members will typically For example, the module may comprise a half-dome, have a length in the range of about 1 x 10"9 m to about which itself may be comprised of tetrahedral, geodesic 1 x 10"1 m, and more typically in the range of about 1 x sub-modules. In certain embodiments, the members 10"6 m to about 1 x 10"2 m. The elongated members may form polyhedral modules with different shaped 25 may be of a constant or varying thickness along their polygonal faces or only a subset of members mapping length, in particular where it is desired to impart local- out geodesic lines. ized flexibility to the structure. Typically, the cross-sec- [0027] The elongated members which comprise the tional diameter of the elongated element is in the range modules are integral members of a single module, that of about 1-1000 urn. is, they are not joined as separate elements but are 30 [0032] In many instances, the scaffold material is formed as a unitary body. In embodiments where some desirably prestressed in order to promote the self -stabi- kinematic properties are desired or where some flexibil- lization of the tensegrity structure. Prestress may be ity at interstices is desired, it may be desired to provide introduced into the scaffold material in a variety of ways. elongated elements having differing cross-sectional By way of example only, the scaffold material may be areas near or at the interstices or vertices. Thus, in one 35 prestressed by incorporating at least one non-com- embodiment, the modules are comprised of elongated pressible member and by contracting the other mem- elements which are "thicker" at the center and "nar- bers of the material around the non-compressible rower" at the vertices. Alternatively, the material proper- member. Prestress may also be introduced by expan- ties of the scaffold material may be varied to provide sion or extension of a non-compressible member which increased compliance in the regions of the vertices, for 40 is enclosed within the scaffold material. Alternatively, example, by altering the cross-linking density of poly- prestress may be imposed by incorporating a second meric material. material, such as a polymer, into the intrascaffold space [0028] The elongated elements may be non-com- of the material. In preferred embodiments, the second pressible elements. Alternatively, the elongated ele- material is a polymer which is capable of swelling and ments may be extensible elements, that is, capable of 45 which upon swelling imposes a stress on the scaffold extension or an increase in length in response to appli- material. Fig. 5 illustrates positioning of a polymer, pref- cation of a tensile stress. Due to materials limitations, it erably a swellable hydropolymer, into interstitial spaces is understood that such extensible properties will be so as to prestress the scaffold material while retaining experienced only over a limited range of motion. An an open pore structure which may be useful in some extensible elongated element is expected to contract in so applications. length when compressed up to a certain point, at which [0033] The scaffold material thus is an open network point it will become non-compressible. Extensible mem- containing at least a portion of geodesic elements which bers include but are not limited to linear (telescoping), may be integrally connected over an extended dimen- curvilinear, helical, spring, sawtooth, crenulated or sion, thereby forming sheets or other shapes as entanglement configurations. The scaffold material of 55 desired. The actual shape of the scaffold material and the present invention may be comprised of all non-com- selection of the module geometries and dimensions pressible elements, all extensible elements or a combi- may be selected to meet the needs of the intended nation of the two. application.

5 9 EP 0 963 834 A1 10

[0034] In one embodiment of the invention, the scaf- as described above, the shell can be filled with a powder fold material may be used for filtration. A rigid octet truss and subjected to high temperature and/or high pressure such as shown in Fig. 4 is an example of a scaffold to sinter the powder to produce a solid article, according material suited for high flowthrough applications such to techniques well-known in the art. The shell may be as air masks, water purification systems, filtration, cata- 5 removed after sintering or may form a part of the final lytic converters for removal of hydrocarbons and other article. Descriptions of sintering fundamentals can be detoxification networks. The open network may be found in "Sintering of Ceramics," Encyc. of Mat. Sci. & impregnated with materials selected for their ability to Eng. 6:4455-4456 (1986) and "Physical Fundamentals remove particulants or chemicals from a medium. Typi- of Consolidation," Metals Handbook, 9th ed., 7:308- cal impregants include, but are in no way limited to, w 321. hydrogels, charcoal particles, liposomes, lipid foams, [0038] In another embodiment of the invention, the detoxifying enzymes or catalysts, affinity binding lig- scaffold material may be prepared in long lengths as a ands, antibodies and optical fibers. The bioactive hydro- textile. A scaffold material incorporating cuboctahedron gels contemplated for use in the invention will modules integrally connected along one edge or face, significantly restrict passage of air, moisture, and heat, 75 as shown in Figs. 6-8, may provide a material which if applied as a solid layer. Thus, it will be necessary to strengthens when compressed and thus may be useful construct these light-weight support scaffolds for the against high force impacts, such as in bullet proof vests hydrogels that maintain open passages for air or umpire vests. In the embodiment illustrated in Fig. 6, exchange, in addition to providing high tensile strength. an array of cuboctrahedron modules is capable of rear- [0035] In another embodiment of the invention, the 20 rangement into an array of octahedral modules. In scaffold material may be incorporated into a pattern for another embodiment, a scaffold material incorporating shell investment casting. In this embodiment, a pattern cuboctahedron modules integrally connected along a is contructed which has a thin, solid outer surface, and single edge, different than that of Fig. 6, is capable of an inner scaffold structure which supports the outer sur- rearrangement into a "dog-leg" geometry and is particu- face. The outer surface may be formed using the same 25 larly well-suited for textiles which may need to compact process which is used to form the scaffold, or may be anisotropically around curved or angular surfaces (Fig. added after forming the scaffold, for example by wrap- 7). Fig. 8 illustrates yet another embodiment, in which ping a flexible material around a shaped scaffold. cuboctahedron modules rearrange into yet another con- [0036] The tensegrity-based structure of the scaffold figuration of octahedral modules. All three materials allows the pattern to be made sufficiently strong to 30 would maintain high flexibility and porosity in their open endure the casting process with a minimum of pattern configuration, while exhibiting high rigidity, strength, and material, and it optimizes porosity. Once formed, the a restriction to flow-through when compacted and thus, surface of the pattern is coated with a hardenable mate- may be useful for construction of filtration systems that rial to form a shell coating. In one embodiment, the automatically shut off and valve themselves at high hardenable material may be a ceramic slurry which is 35 pressure. cured to form a ceramic mold. The scaffold material is [0039] In another embodiment, the textile may be then eliminated by a method such as flash firing, leaving adapted for use as battledress overgarments (BDO) for behind a shell suitable for casting metal or polymer pans protection against biological or chemical toxins. Con- in the shape of the original pattern. Techniques of form- ventional BDOs rely on use of activated charcoal parti- ing a shell mold from a pattern for subsequent casting 40 cles or other means to absorb air-borne chemical are well-known in the art, and are described in "Invest- toxins. They offer little or no protection against biological ment Casting," Encyc. of Mat Sci. & Eng. 3:2398-2402 toxins or pathogens. To be effective against biological (1 986) and Stereolithography and other RP&M Technol- threats at high concentrations, the scaffold material of ogies. Society of Manufacturing Engineers 183-185 the present invention may be fabricated to exhibit high (1 996). An advantage of incorporating the types of scaf- 45 porosity and tortuosity to permit pathogen entry and air fold material described herein into an investment cast- passage while physically restricting pathogen penetra- ing pattern is that the amount of material necessary to tion. To ensure efficient biothreat removal, the fabric support the shell mold is reduced compared to conven- desirably exhibits a high surface area to volume ratio tional patterns, reducing the amount of ash which is and contains molecular ligands and enzymes that bind, generated in firing. Further, these scaffolds contract so sequester, and destroy toxins and pathogens with high more efficiently than conventionally used porous plastic efficiency. To facilitate binding interactions and support patterns, and thus minimize expansive cracking of enzymatic activities, the material desirably retains a sig- ceramic molds. nificant amount of water and thus is organized, at least [0037] In a related embodiment, a similar pattern may in part, as a "hydrogel." The water phase also may be used to make a mold for sintering. In this embodi- ss enhance removal of biological and chemical agents ment, the pattern is used to produce a shell by forming contained within air-borne water droplets as the air a hardenable material around the pattern as in the pre- passes through the high surface area of the lattice and vious embodiment. Once the pattern has been removed thereby, further increase the efficiency of pathogen cap-

6 11 EP 0 963 834 A1 12 ture. In one embodiment of the present invention, the and toxins may be bound and sequestered by conjugat- scaffold material is desirably coated with or impreg- ing these specific ligands to the backbone of a hydrogel nated with a hydrogel. which has been impregnated into the scaffold material. [0040] Suitable hydrogels include, but are not limited [0044] A technique has been developed to coat to, poly(2-hydroxyethyl methacrylate-co-methyl meth- s poly(HEMA) hydrogels onto porous scaffolds, including acrylate), copolymers of methacrylic acid (MAA), acrylic geodesic scaffold cassettes fabricated using stereo- acid (AA), and/or glycidyl methacrylate (GMA), unsatu- lithography. The procedure consists of an initial pre- rated linear polyesters, and poly(ethylene glycol). In the coating process using HEMA/alcohol solution, followed preparation of poly(2-hydroxyethyl methacrylate-co- by polymerization of HEMA and the crosslinking agent methyl methacrylate), the monomers, 2-hydroxy ethyl 10 EGDMA in 0.7 M NaCI using a redox initiating system. A methacrylate (HEMA) and methyl methacrylate (MMA), uniform hydrogel coating can be obtained using this are liquid and can be mixed with a crosslinking agent method. The thickness of the hydrogel coating is con- (ethyleneglycol dimethacrylate, EGDMA) and an initia- trolled by the concentration of monomer and initiator, as tor to polymerize and form a hydrogel. The relative well as coating time. amount of 2-hydroxyethyl methacrylate confers is [0045] The scaffold material of the present invention hydrophilicity and also pliability whereas the methyl may be prepared using well known polymer synthesis methacrylate confers hydrophobicity and mechanical and microfabrication techniques including, but not lim- rigidity to the hydrogel. The engineering of the ited to, stereolithography, three dimensional microprint- HEMA/MMA copolymer ratio and the EDGMA crosslinking, microscale patterning and micromolding ing ratio allows one to synthesize hydrogels with tailored 20 techniques. These fabrication techniques may be facili- perinselective and mechanical properties. tated by the use of mathematical models for cell and [0041 ] The tensile strengths and moduli of the materi- cytoskeletal mechanics based on tensegrity. These als may be determined by an axial/torsional test system. mathematical principles are described in "A Microstruc- Water binding capacities can be measured in dynamic tural Approach to Cytoskeletal Mechanics based on and equilibrium swelling studies. Porosity and pore size 25 Tensegrity" J. Theor. Biol. 181:125 (1996), which is of dry specimens can be measured by mercury intru- found in Appendix I. The two parameters that determine sion porosimetry. The porosity and pore size of wet the mechanical stability of tensegrity structures are pre- specimens can be estimated morphometrically using stress and architecture. Prestress determines the initial environmental scanning electron microscopy. Fig. 9a stiffness of the structure and ensures that it will respond illustrates a scaffold material which has been coated 30 immediately when external force is applied. Architecture with a hydrogel. describes the number of different building elements and [0042] It also should be possible to provide additional how they distribute forces in space. This geometric fea- protective activity against biothreat agents by incorpo- ture determines how the different structural elements rating enzymes (e.g., proteases to breakdown toxins; rearrange and thus, how the entire structure stiffens in enzymes that generate free radicals in the gel). In addi- 35 response to stress. This mathematical treatment pro- tion, enzymes that bind, inactivate, and/or destroy vides an entirely new quantitative method for analyzing chemical toxins, such as organophosphorus nerve the mechanical properties of any natural system that gases (e.g., acetylcholinesterase, organophosphorus exhibits linear stiffening behavior, regardless of size. acid anhydrolase, phosphotriesterase), also could be [0046] Tensegrity structures can be complex, how- incorporated within the gel to provide additional protec- 40 ever, and equations and analytical solutions alone may tion against these chemical warfare agents. By way of not give the full picture of how these structural networks example only, acetylcholinesterase enzyme may be react to external forces. For this reason, computer mod- conjugated to a hydrogel using carbonyl-diimidazole eling and animation techniques may be used to simu- and the activity of the immobilized enzyme analyzed in late and explore dynamic geometric transformations vitro using conventional biochemical techniques. The 45 within three dimensional (3D) tensegrity lattices as an efficiency of protein binding also can be assessed by aid to the design of the scaffold materials of the inven- radiolabeling or surface analysis (X-ray photoelectron tion. This CAD capability makes possible the designing spectroscopy). of synthetic networks with desired mechanical, struc- [0043] Biological toxins (e.g., ricin toxin, botulinum tural, and geometric features. For example, the compu- toxin, Vibrio cholerae neuraminidase) and pathogenic so ter-generated time sequences depicted in Figs. 6-8 organisms (e.g., bacteria, viruses, protozoa) adhere to show highly flexible and porous lattices containing large living cells and enter the body by binding to specific lig- central pores undergoing progressive geometric trans- ands on the cell surface, including simple sugars (e.g., formations (left and right columns are top and side galactose), complex carbohydrates (e.g.. heparan sul- views of the same structure, respectively). Note that the fate), and membrane phospholipids (e.g., phosphatidyl- 55 loose, open lattices progressively fold in on themselves, inositol). Monoclonal antibodies also have been gener- close their central pores, and mechanically stiffen (reor- ated which bind to specific biothreat agents with high ganizes into stable octagonal and tetrahedral forms), affinity (e.g., ricin toxin). These pathogenic organisms without breaking any structural connections. A synthetic

7 13 EP 0 963 834 A1 14 polymer lattice fabricated with the same geometric fea- adapted to develop bioerodible polymer scaffolds for tis- tures offers a similar ability to vary network mechanics, sue engineering or biomimetic erythrocytes (bioerodible organization, and porosity, without loss of structural nanosponges) that can be injected intravascularly to integrity. Furthermore, the mechanical strength of these soak up and neutralize pathogens in vivo. Possible flexible network can be greatly increased, by incorporat- 5 materials for such applications include, but are not lim- ing larger, less flexible struts (e.g., long carbon fibers) ited to, polyglycolic acid, polylactic acid, polyimide, within the framework as shown in Figure 10. A similar polyamide, polyester, protein, carbohydrate, nucleic approach may be used to generate anisotropic behavior acid, and lipid. in different regions of biomimetic textile fabrics (e.g., [0050] Other well-known microfabrication techniques over a knee joint). ro may be used in the preparation of the scaffold material. [0047] In recent years, manufacturers have been fore- By way of example only, stereolithography techniques, going blueprints and drawing boards in favor of worksta- three dimensional microprinting, three dimensional tions and CAD/CAM software. Using commercial laser-based drilling or etching techniques, micromold- software, engineers are able to convert CAD drawings ing, and self-assembly methods may be used in the into interactive, high-resolution 3D models. They can is preparation of the material of the invention. The inter- rotate parts and check them for form, fit, and function ested reader is directed to Science and Technology of without ever holding a part in their hands. Using linked Microfabrication R.E. Howard, E. L Hu, S. Namba, S. CAD/CAM systems they can directly translate design Pang (Eds.) Materials Research Society Symposia Vol. into product. At the same time, work with materials man- 76 (1987), for further information on microfabrication. ufactured for the aerospace and automobile industries, 20 [0051 ] A typical scaffold material that could be used and particularly with composite materials, has revealed for a protective air mask filtration device has been pre- that the microstructure of these materials (e.g., dimen- pared as described in the following example. sion and orientation of fibers) largely determines their [0052] A CAD application was used to design a three mechanical properties. In these materials, most fea- dimensional network. Several commercially available tures of the microstructure are beyond the control of the 25 programs, including ProEngineer (Parametrics Technol- design/manufacturing process. These small scale struc- ogy Corporation) and Ideas (Structural Dynamics tural features are created essentially as an artifact as Research Corporation), have been found suitable for the material is being formed into its final shape using designing the network. The network consisted of an conventional processes such as injection or compres- octet truss such as shown in Fig. 4, with member sion molding. 30 lengths of about 800 urn and member transverse cross- [0048] Combination of CAD technology with CAM sectional diameters of about 150 urn. All struts were ori- software allows fabrication of scaffold materials with ented at 60 degree angles relative to neighboring mem- defined geodesic and tensegrity-based microstructures bers, resulting in the formation of a continuous array of which have been identified as desirable. Specifically, closely packed tetrahedron modules with octahedral CAD capability may be combined with CAM technology 35 intermodule spaces or what is known as an "octet based on stereolithography. In stereolithography, a liq- truss." The scaffold material has been fabricated using uid polymer resin is selectively polymerized (solidified) both epoxy and acrylate resins, using CAM in combina- by a laser beam chat is under the control of a computer tion with a 3D Systems SLA-250 Stereolithography to construct a polymeric material with 3D microstruc- apparatus (3D Systems, Valencia, CA). This apparatus, tural features that precisely match those specified using 40 modified to include a TEM 00 laser, can produce up to CAD. The construction process involves fabrication of 23" cube of polymer composed of a unitary epoxy or sequential chin cross section layers (analogous to tom- acrylate resin with the finest line features (elongated ographic sections), one being polymerized atop the members) of about 70 urn2 in cross-sectional area. other, until the entire 3D material is completed. Using [0053] Once formed, the scaffold was immersed in liq- this approach, 3D porous polymer networks can be fab- 45 uid hydrogel resin containing HEMA and EGDMA, then ricated with any microstructure that can be created purged with air to remove most free resin. The residual using CAD. Although epoxy-based resins are most com- resin adherent to the surface of the scaffold material monly used in this technique, in theory, any chemical was polymerized in 0.7 M NaCI using a redox initiating that may be polymerized using a UV-sensitive initiator system to form a hydrogel coating as visualized in Fig. may be utilized. An octet truss configuration, composed so 9a. This hydrogel could in turn be chemically conju- of closedly packed octahedra and tetrahedra, has been gated to biactive molecules such as carbohydrates con- produced using both epoxy and acrylate resins using taining galactose dimers to remove ricin toxins, stereolithography. antibodies against different pathogenic organisms, and [0049] This CAD capability allows the design and fab- enzymes, such as acetylcholinesterase, that may deac- rication of materials with capabilities never previously 55 tivate nerve gases. The scaffold spaces could also be considered. By way of example, the same approach that impregnated with charcoal microparticles (Fig. 9b) to leads to development of mechanically strong and light remove air-borne chemical toxins as well as liposomes polymer skins for pathogen neutralization may be or lipid foams to remove lipophilic agents and organ-

8 15 EP 0 963 834 A1 16 isms. 4. The material of para 1 , wherein said elongated [0054] A prototypical flexible array of cuboctahedrons members are substantially non-compressible. has also been produced using Dupont SOMOS 2100 5. The material of para 1 in which a first portion of polymer. The prototype, illustrated in Figure 13c and said members are substantially non-compressible 13d, consisted of two linked cuboctahedra, but larger 5 and a second portion of said members are extensi- arrays could be made by the same techniques. ble. [0055] The flexible array was made using the same 6. The material of para 1 or 2, wherein said mod- CAD/CAM systems used to manufacture the octet truss ules comprise a subset of members oriented as described above. The prototype constructed had a non-geodesic four-sided polygonal elements. height of 33mm in the fully expanded configuration, and 10 7. The material of para 1 or 3, wherein said polyhe- a height of 1 7mm in the contracted configuration shown dral module comprises eight triangular elements in Figure 13d. The prototype was found to deform rela- integrally connected at their common vertices. tively easily as the cuboctahedrons collapsed into octa- 8. A scaffold material, comprising: hedrons, and then to stiffen considerably. This behavior was in accord with computer models of this configura- 15 a predetermined arrangement of integrally con- tion. Figures 13a and 13b depict computer models of nected modules, each said module comprised the prototype in an expanded and a contracted configu- of a plurality of integrally connected, elongated, ration. A large array made using the principles of this extensible members forming a least a portion prototype would maintain high flexibility and porosity in of a polyhedron, the members arranged such the open configuration, while exhibiting high rigidity, 20 that all said members form geodesic elements. strength, and a restriction to flow-through when compacted and thus, could be useful for construction of fil- 9. The material of para 8, wherein said extensible tration systems that automatically shut off and valve member is selected from the group consisting of lin- themselves at high pressure. ear, curvilinear, helical, spring, sawtooth form, [0056] Another example of a scaffold material which 25 crenulated, and entanglement elements. can be made using CAD/CAM is a cuboctahedron scaf- 10. The material of para 1, 2, 3, or 8, wherein said fold in which vertices are narrowed so as to permit module is selected from a set comprising a sphere, greater flexibility in the material. By way of example, a portion of a sphere, an icosahedron, an octahe- each member is about 1 mm in length, about 275 urn in dron, a dodecahedron, tetrahedron, and truncated cross-section diameter at its center and about 250 urn so30 or stellated forms of these geodesic polyhedra. in diameter at each vertex. Such a scaffold would 1 1 . The material of para 1,2,3, or 8, wherein said behave much like the flexible prototype described arrangement comprises a plurality of said modules above, except that flow-through would still be possible integrally connected by sharing one or more com- even in the compacted configuration, since the two- mon vertices, edges, faces or intersections. dimensional triangle elements would be replaced by 35 12. The scaffold material of para 1, 2, 3 or 8, one-dimensional struts along the edges of the triangles. wherein said members have an elongated dimen- [0057] Other embodiments of the invention will be sion in the range of about 1 x 10"9 to about 1 x 10"1 apparent to those skilled in the art from a consideration meter. of the specification or practice of the invention disclosed 13. The scaffold material of para 1, 2, 3 or 8, herein and, in particular they may include the features 40 wherein the arrangement of the geodesic or listed in the following enumerated paragraphs ("paras"). tensegrity elements results in a structure having intermember pores in the range of about 1 x 10"9 to 1 . A scaffold material, comprising: about 1 x 10"1 meter. 14. The scaffold material of para 1, 2, 3, or 8, a predetermined arrangement of integrally con- 45 wherein at least one module is prestressed. nected modules, each said module comprised 15. The scaffold of para 14, wherein said prestress of a plurality of integrally connected elongated is imposed by a polymer located within the at least members forming at least a portion of a polyhe- one module. dron, the members arranged such that at least 16. The scaffold material of para 15, wherein said a portion of said members form geodesic or so polymer is a hydrogel capable of swelling when tensegrity elements. placed in contact with an aqueous medium. 1 7. The scaffold material of para 1 6, wherein said 2. The material of para 1 , wherein said modules are hydrogel polymer is composed of poly(2-hydroxye- capable of rearranging to form a fully geodesic or thyl methacrylate-co-methyl methacrylate), unsatu- tensegrity structure. 55 rated linear polyesters and poly(ethylene glycol), 3. The material of para 1, wherein all members copolymers of methacrylic acid, acrylic acid, and/or within all said modules form geodesic or tensegrity glycidal methacrylate. elements. 18. The material of para 1, 2, 3 or 8, further com-

9 17 EP 0 963 834 A1 18 prising a hydrogel polymer coated onto at least a microprinting, three dimensional laser-based drill- portion of the elongated members. ing or etching, and self-assembly techniques. 19. The scaffold material of para 18, wherein said 34. The scaffold material of para 1, 2, 3, or 8, hydrogel polymer is composed of poly(2-hydroxye- wherein a portion of the modules is derivatized with thyl methacrylate-co-methyl methacrylate), unsatu- s biologically or chemically active molecules. rated linear polyesters and poly(ethylene glycol), 35. The scaffold material of para 1, 2, 3, or 8, copolymers of methacrylic acid, acrylic acid, and/or wherein the surface of said material is coated with glycidal methacrylate. a polymer. 20. The scaffold material of para 18, wherein said 36. The scaffold material of para 35, wherein the polymer is derivatized with biologically or chemi- 10 said coating polymer is derivatized with biologically cally active molecules. or chemically active processing molecules. 21. The scaffold material of para 15, wherein said 37. The scaffold material of para 1, 2, 3, or 8, polymer is capable of expansion upon exposure to wherein the scaffold forms the internal structure of heat, change in pH, change in electrical charge or a pattern for a manufactured article. other environmental condition. is 38. The scaffold of para 37, wherein the pattern is a 22. The scaffold of para 14, wherein said prestress pattern for investment casting. is imposed by incorporating at least one non-com- 39. The scaffold of para 37, wherein the manufac- pressible member. tured article is to be formed by sintering. 23. The scaffold of para 22, wherein said prestress 40. A pattern for a manufactured article, comprising is imposed by contraction of the scaffold material 20 around said at least one non-compressible mem- solid outer surfaces forming the shape of the ber. article to be manufactured, and 24. The scaffold of para 22, wherein said prestress an internal scaffold material, comprising a pre- is imposed by expansion of the at least one non- determined arrangement of integrally con- compressible member into contact with the scaffold 25 nected modules, each said module comprised material. of a plurality of integrally connected elongated 25. The scaffold material of para 1, 2, 3, or 8, members forming at least a portion of a polyhe- wherein said members of said module define at dron, the members arranged such that at least least one intermember space and the at least one a portion of said members form geodesic or intermember space is filled with a solid material. 30 tensegrity elements. 26. The scaffold material of para 25, wherein said solid material is an elastomer. 41 . The pattern of para 40, wherein the article is to 27. The scaffold material of para 26, wherein said be manufactured by investment casting. elastomer is selected from the group consisting of 42. The pattern of para 40, wherein the article is to unsaturated linear polyesters and poly(ethylene 35 be manufactured by sintering. glycol), polyurethane, and polydimethylsiloxane. 43. A method of creating a mold for manufacturing, 28. The scaffold material of para 1, 2, 3, or 8, comprising: wherein the structural members are composed of non-erodible polymers. (a) providing a pattern in the shape of an article 29. The scaffold material of para 28, wherein said 40 to be manufactured, comprising: polymer is selected from the group consisting of polyacrylates, polyepoxides, polyesters, poly- (i) solid outer surfaces, and urethanes, poly(methacrylic acid), poly(acrylic (ii) an internal scaffold material, compris- acid), polyimides, and polysiloxanes. ing a predetermined arrangement of inte- 30. The scaffold material of para 1, 2, 3, or 8, 45 grally connected modules, each said wherein the structural members are composed of module comprised of a plurality of inte- erodible polymers. grally connected elongated members 31. The scaffold material of para 30, wherein the forming at least a portion of a polyhedron, structural members are selected from the group the members arranged such that at least a consisting of polyglycolic acid, polylactic acid, poly- so portion of said members form geodesic or iimide, polyamide, polyester, protein, carbohydrate, tensegrity elements, nucleic acid, and lipid. 32. The scaffold material of para 1, 2, 3, or 8, (b) coating the pattern with a hardenable mate- wherein the said material is fabricated using com- rial, puter aided manufacturing techniques. 55 (c) transforming the hardenable material into a 33. The scaffold material of para 32, wherein said hard shell mold, and material is fabricated using at least one of stereo- (d) removing the pattern from the shell without lithography, micromolding, three dimensional breaking the hard shell mold.

10 19 EP 0 963 834 A1 20

44. The method of para 43, wherein the mold is to members forming at least a portion of a polyhe- be used for casting a metal, ceramic, glass, or pol- dron, the members arranged such that at least ymer article. a portion of said members form geodesic or 45. A method of investment casting, comprising: tensegrity elements. 5 (a) providing a pattern in the shape of an article 4. A method of creating a mold for manufacturing, to be formed by casting, comprising: comprising:

(i) solid outer surfaces, and (a) providing a pattern in the shape of an article (ii) an internal scaffold material, compris- 10 to be manufactured, comprising: ing a predetermined arrangement of integrally connected modules, each said (i) solid outer surfaces, and module comprised of a plurality of inte- (ii) an internal scaffold material, compris- grally connected elongated members ing a predetermined arrangement of inte- forming at least a portion of a polyhedron, rs grally connected modules, each said the members arranged such that at least a module comprised of a plurality of inte- portion of said members form geodesic or grally connected elongated members tensegrity elements, forming at least a portion of a polyhedron, the members arranged such that at least a (b) coating the pattern with a hardenable mate- 20 portion of said members form geodesic or rial, tensegrity elements, (c) transforming the hardenable material into a hard shell, (b) coating the pattern with a hardenable mate- (d) removing the pattern from the shell without rial, breaking the shell, and 25 (c) transforming the hardenable material into a (e) casting the article by filling the shell with liq- hard shell mold, and uid which is subsequently transformed into a (d) removing the pattern from the shell without solid. breaking the hard shell mold.

Claims 30 5. A method of investment casting, comprising:

1 . A scaffold material, comprising: (a) providing a pattern in the shape of an article to be formed by casting, comprising: a predetermined arrangement of integrally connected modules, each said module comprised 35 (i) solid outer surfaces, and of a plurality of integrally connected elongated (ii) an internal scaffold material, compris- members forming at least a portion of a polyhe- ing a predetermined arrangement of inte- dron, the members arranged such that at least grally connected modules, each said a portion of said members form geodesic or module comprised of a plurality of inte- tensegrity elements. 40 grally connected elongated members forming at least a portion of a polyhedron, 2. A scaffold material, comprising: the members arranged such that at least a portion of said members form geodesic or a predetermined arrangement of integrally con- tensegrity elements, nected modules, each said module comprised 45 of a plurality of integrally connected, elongated, (b) coating the pattern with a hardenable mate- extensible members forming at least a portion rial, of a polyhedron, the members arranged such (c) transforming the hardenable material into a that all said members form geodesic elements. hard shell, 50 (d) removing the pattern from the shell without 3. A pattern for a manufactured article, comprising: breaking the shell, and (e) casting the article by filling the shell with liq- solid outer surfaces forming the shape of the uid which is subsequently transformed into a article to be manufactured, and solid. an internal scaffold material, comprising a pre- 55 determined arrangement of integrally connected modules, each said module comprised of a plurality of integrally connected elongated

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European Patent Application Number J EUROPEAN SEARCH REPORT Office EP 98 30 4496

DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document with indication, where appropriate. Relevant CLASSIFICATION OF THE of relevant passages to claim APPLICATION (lnt.CI.6) D,X US 4 207 715 A (KITRICK CHRISTOPHER J) 1,2 B29C67/00 17 June 1980 B22C7/02 * the whole document * E04G1/00 A61L27/00 X US 5 732 518 A (ROBERTS PETER A) 1,2 D04H13/00 31 March 1998 B01D39/14 Y * the whole document * 3-5

Y EP 0 649 691 A (TEXAS INSTRUMENTS INC) 3-5 26 April 1995 * the whole document *

EP 0 655 317 A (IBM) 31 May 1995 3-5 * column 2, line 25 - line 44 *

EP 0 590 957 A (CMET INC) 6 April 1994 3-5 * column 1, line 21 - line 32; figure 2 * * column 8, line 4 - line 35; figures 9,10 *

DE 195 07 881 A (MATERIALISE NV) 4,5 TECHNICAL FIELDS SEARCHED (Int. CI. 6) 14 September 1995 * the whole document * B29C B22C E04G A61L E04B D04H B01D

The present search report has been drawn up for all claims Place of search Date of completion of the search Examiner THE HAGUE 11 November 1998 Mathey, X CATEGORY OF CITED DOCUMENTS T : theory or principle underlying the invention E : earlier patent document, but published on, or X : particularly relevant if taken alone after the filing date Y : particularly relevant if combined with another D : document cited in the application document of the same category L : document cited for other reasons A : technological background O : non-written disclosure & : member of the same patent family, corresponding P : intermediate document document