An Overview of Mechanical Tests for Polymeric Biomaterial Scaffolds Used in Tissue Engineering

Oscar Robles Vazquez; Ignacio Orozco Avila; Juan C. Sánchez Díaz; Elena Hernandez

doi:10.6000/1929-5995.2015.04.04.1

Authors

Oscar Robles Vazquez Departamento de Ingeniería Química, CUCEI, Universidad de Guadalajara, 44430 Guadalajara, México
Ignacio Orozco Avila Tecnología Alimentaria, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, A. C., CIATEJ, 44270 Guadalajara, México
Juan C. Sánchez Díaz Departamento de Ingeniería Química, CUCEI, Universidad de Guadalajara, 44430 Guadalajara, México
Elena Hernandez Departamento de Ingeniería Química, CUCEI, Universidad de Guadalajara, 44430 Guadalajara, México

DOI:

https://doi.org/10.6000/1929-5995.2015.04.04.1

Keywords:

Hydrogel, membrane, soft material, elastic modulus, rubber elasticity, uniaxial test, compression test.

Abstract

Mechanical characterization of polymeric biomaterial scaffolds is essential to allow biomaterials that interface with tissues and tissue engineered constructs to be developed with appropriate mechanical strength. However, the fragility of these materials makes their mechanical characterization in a quantitative manner highly challenging. Here we report an overview of testing techniques for the characterization of mechanical properties of films, membranes, hydrogels and fibers commonly used as scaffolds in tissue engineering applications.

References

Yoon DM, Fisher JP. Polymeric scaffolds for tissue engineering applications. In: Fisher JP, Mikos AG, Bronzino JD, editors. Tissue Engineering. Boca Raton: CRC Press; 2007; p. 8.1-8.18. http://dx.doi.org/10.1201/9781420008333.sec2 DOI: https://doi.org/10.1201/9781420008333.sec2

Liu C, Xia Z, Czernuszka JT. Design and development of three-dimensional scaffolds for tissue engineering. Chem Eng Res Des 2007; 85: 1051-64. http://dx.doi.org/10.1205/cherd06196 DOI: https://doi.org/10.1205/cherd06196

Khademhosseini A, Vacanti JP, Langer R. Progress in tissue engineering. Sci Am 2009; 300: 64-100. http://dx.doi.org/10.1038/scientificamerican0509-64 DOI: https://doi.org/10.1038/scientificamerican0509-64

Biondi M, Ungaro F, Quaglia F, Netti PA. Controlled drug delivery in tissue engineering. Adv Drug Deliv Rev 2008; 60: 229-42. http://dx.doi.org/10.1016/j.addr.2007.08.038 DOI: https://doi.org/10.1016/j.addr.2007.08.038

Hutmacher D, Woodfield T, Dalton P, Lewis J. Scaffold design and fabrication. In: van Blitterswijk C, Thomsen P, Lindahl A, et al., editors. Tissue Engineering. Academic Press Series in Biomedical Engineering. London: Academic Press; 2008. p. 403-54. http://dx.doi.org/10.1016/b978-0-12-370869-4.00014-8 DOI: https://doi.org/10.1016/B978-0-12-370869-4.00014-8

Stamatialis DF, Papenburg BJ, Girons M, et al. Medical applications of membranes: Drug delivery, artificial organs and tissue engineering. J Memb Sci 2008; 308: 1-34. http://dx.doi.org/10.1016/j.memsci.2007.09.059 DOI: https://doi.org/10.1016/j.memsci.2007.09.059

Temtem M, Silva LMC, Andrade PZ, et al. Supercritical CO2 generating chitosan devices with controlled morphology. Potential application for drug delivery and mesenchymal stem cell culture. J Supercrit Fluids 2009; 48: 269-77. http://dx.doi.org/10.1016/j.supflu.2008.10.020 DOI: https://doi.org/10.1016/j.supflu.2008.10.020

Dimitru S. Polymeric Biomaterials. 2nd ed: Marcel Decker; 2002.

Slaughter BV, Khurshid SS, Fisher OZ, Khademhosseini A, Peppas NA. Hydrogels in regenerative medicine. Adv Mater 2009; 21: 3307-29. http://dx.doi.org/10.1002/adma.200802106 DOI: https://doi.org/10.1002/adma.200802106

Hou Y, Schoener CA, Regan KR, Munoz-Pinto D, Hahn MS, Grunlan MA. Photo-Cross-linked PDMS star-PEG hydrogels: synthesis, characterization, and potential application for tissue engineering scaffolds. Biomacromolecules 2010; 11: 648-56. http://dx.doi.org/10.1021/bm9012293 DOI: https://doi.org/10.1021/bm9012293

Kretlow JD, Klouda L, Mikos AG. Injectable matrices and scaffolds for drug delivery in tissue engineering. Adv Drug Deliv Rev 2007; 59: 263-73. http://dx.doi.org/10.1016/j.addr.2007.03.013 DOI: https://doi.org/10.1016/j.addr.2007.03.013

Anseth KS, Bowman CN, Brannon-Peppas L. Mechanical properties of hydrogels and their experimental determination. Biomaterials 1996; 17: 1647-57. http://dx.doi.org/10.1016/0142-9612(96)87644-7 DOI: https://doi.org/10.1016/0142-9612(96)87644-7

Ahearne M, Siamantouras E, Yang Y, Liu KK. Mechanical characterization of biomimetic membranes by micro-shaft poking. J R Soc Interface 2009; 6: 471-8. http://dx.doi.org/10.1098/rsif.2008.0317 DOI: https://doi.org/10.1098/rsif.2008.0317

Buckley CT, Thorpe SD, O'Brien FJ, Robinson AJ, Kelly DJ. The effect of concentration, thermal history and cell seeding density on the initial mechanical properties of agarose hydrogels. J Mech Behav Biomed Mater 2009; 2: 512-21. http://dx.doi.org/10.1016/j.jmbbm.2008.12.007 DOI: https://doi.org/10.1016/j.jmbbm.2008.12.007

Hafemann B, Ensslen S, Erdmann C, et al. Use of a collagen/elastin-membrane for the tissue engineering of dermis. Burns 1999; 25: 373-84. http://dx.doi.org/10.1016/S0305-4179(98)00162-4 DOI: https://doi.org/10.1016/S0305-4179(98)00162-4

Majima T, Funakosi T, Iwasaki N, et al. Alginate and chitosan polyion complex hybrid fibers for scaffolds in ligament and tendon tissue engineering. J Orthop Sci 2005; 10: 302-7. http://dx.doi.org/10.1007/s00776-005-0891-y DOI: https://doi.org/10.1007/s00776-005-0891-y

Huang AH, Yeger-McKeever M, Stein A, Mauck RL. Tensile properties of engineered cartilage formed from chondrocyte- and MSC-laden hydrogels. Osteoarthr Cartil 2008; 16: 1074-82. http://dx.doi.org/10.1016/j.joca.2008.02.005 DOI: https://doi.org/10.1016/j.joca.2008.02.005

Ahearne M, Yang Y, El Haj AJ, Then KY, Liu KK. Characterizing the viscoelastic properties of thin hydrogel-based constructs for tissue engineering applications. J R Soc Interface 2005; 2: 455-63. http://dx.doi.org/10.1098/rsif.2005.0065 DOI: https://doi.org/10.1098/rsif.2005.0065

Nguyen VB, Wang CX, Thomas CR, Zhang Z. Mechanical properties of single alginate microspheres determined by microcompression and finite element modelling. Chem Eng Sci 2009; 64: 821-9. http://dx.doi.org/10.1016/j.ces.2008.10.050 DOI: https://doi.org/10.1016/j.ces.2008.10.050

Chou AI, Akintoye SO, Nicoll SB. Photo-crosslinked alginate hydrogels support enhanced matrix accumulation by nucleus pulposus cells in vivo. Osteoarthr Cartil 2009; 17: 1377-84. http://dx.doi.org/10.1016/j.joca.2009.04.012 DOI: https://doi.org/10.1016/j.joca.2009.04.012

Banerjee A, Arha M, Choudhary S, et al. The influence of hydrogel modulus on the proliferation and differentiation of encapsulated neural stem cells. Biomaterials 2009; 30: 4695-9. http://dx.doi.org/10.1016/j.biomaterials.2009.05.050 DOI: https://doi.org/10.1016/j.biomaterials.2009.05.050

Hsieh WC, Chang CP, Lin SM. Morphology and characterization of 3D micro-porous structured chitosan scaffolds for tissue engineering. Colloids Surf B Biointerfaces 2007; 57: 250-5. http://dx.doi.org/10.1016/j.colsurfb.2007.02.004 DOI: https://doi.org/10.1016/j.colsurfb.2007.02.004

Depan D, Kumar AP, Singh RP. Cell proliferation and controlled drug release studies of nanohybrids based on chitosan-g-lactic acid and montmorillonite. Acta Biomater 2009; 5: 93-100. http://dx.doi.org/10.1016/j.actbio.2008.08.007 DOI: https://doi.org/10.1016/j.actbio.2008.08.007

Wan Y, Wu Q, Wang S, Zhang SM, Hu ZL. Mechanical properties of porous polylactide/chitosan blend membranes. Macromol Mater Eng 2007; 292: 598-607. http://dx.doi.org/10.1002/mame.200600481 DOI: https://doi.org/10.1002/mame.200600481

Duan B, Yuan XY, Zhu Y, et al. A nanofibrous composite membrane of PLGA-chitosan/PVA prepared by electrospinning. Eur Polym J 2006; 42: 2013-22. http://dx.doi.org/10.1016/j.eurpolymj.2006.04.021 DOI: https://doi.org/10.1016/j.eurpolymj.2006.04.021

Thierry B, Merhi Y, Silver J, Tabrizian M. Biodegradable membrane-covered stent from chitosan-based polymers. J Biomed Mater Res A 2005; 75: 556-66. http://dx.doi.org/10.1002/jbm.a.30450 DOI: https://doi.org/10.1002/jbm.a.30450

Liu Y, Vrana NE, Cahill PA, McGuinness GB. Physically Crosslinked Composite Hydrogels of PVA With Natural Macromolecules: Structure, Mechanical Properties, and Endothelial Cell Compatibility. J Biomed Mater Res B 2009; 90: 492-502. http://dx.doi.org/10.1002/jbm.b.31310 DOI: https://doi.org/10.1002/jbm.b.31310

Costa ED, Mansur HS. Preparation and characterization of chitosan/poly(vinyl alcohol)blend chemically crosslinked by glutaraldehyde for tissue engineering application. Quimica Nova 2008; 31: 1460-6.

Ma D, Zhang LM, Yang C, Yan L. UV photopolymerized hydrogels with beta-cyclodextrin moieties. J Polym Res 2008; 15: 301-7. http://dx.doi.org/10.1007/s10965-007-9171-1 DOI: https://doi.org/10.1007/s10965-007-9171-1

Rafat M, Li FF, Fagerholm P, et al. PEG-stabilized carbodiimide crosslinked collagen-chitosan hydrogels for corneal tissue engineering. Biomaterials 2008; 29: 3960-72. http://dx.doi.org/10.1016/j.biomaterials.2008.06.017 DOI: https://doi.org/10.1016/j.biomaterials.2008.06.017

Wan Y, Fang Y, Wu H, Cao XY. Porous polylactide/chitosan scaffolds for tissue engineering. J Biomed Mater Res A 2007; 80: 776-89. http://dx.doi.org/10.1002/jbm.a.31025 DOI: https://doi.org/10.1002/jbm.a.31025

Wang XH, Yan YN, Xiong Z, et al. Preparation and evaluation of ammonia-treated collagen/chitosan matrices for liver tissue engineering. J Biomed Mater Res B 2005; 75: 91-8. http://dx.doi.org/10.1002/jbm.b.30264 DOI: https://doi.org/10.1002/jbm.b.30264

Duan B, Wu LL, Yuan XY, et al. Hybrid nanofibrous membranes of PLGA/chitosan fabricated via an electrospinning array. J Biomed Mater Res A 2007; 83: 868-78. http://dx.doi.org/10.1002/jbm.a.31408 DOI: https://doi.org/10.1002/jbm.a.31408

Correlo VM, Boesel LF, Pinho E, et al. Melt-based compression-molded scaffolds from chitosan-polyester blends and composites: morphology and mechanical properties. J Biomed Mater Res A 2009; 91: 489-504. http://dx.doi.org/10.1002/jbm.a.32221 DOI: https://doi.org/10.1002/jbm.a.32221

Madihally SV, Matthew HWT. Porous chitosan scaffolds for tissue engineering. Biomaterials 1999; 20: 1133-42. http://dx.doi.org/10.1016/S0142-9612(99)00011-3 DOI: https://doi.org/10.1016/S0142-9612(99)00011-3

Tang YF, Du YM, Li Y, Wang XY, Hu XW. A thermosensitive chitosan/poly(vinyl alcohol) hydrogel containing hydroxyapatite for protein delivery. J Biomed Mater Res A 2009; 91: 953-63. http://dx.doi.org/10.1002/jbm.a.32240 DOI: https://doi.org/10.1002/jbm.a.32240

Nagahama H, Maeda H, Kashiki T, Jayakumar R, Furuike T, Tamura H. Preparation and characterization of novel chitosan/gelatin membranes using chitosan hydrogel. Carbohydr Polym 2009; 76: 255-60. http://dx.doi.org/10.1016/j.carbpol.2008.10.015 DOI: https://doi.org/10.1016/j.carbpol.2008.10.015

Sarasam A, Madihally SV. Characterization of chitosan-polycaprolactone blends for tissue engineering applications. Biomaterials 2005; 26: 5500-8. http://dx.doi.org/10.1016/j.biomaterials.2005.01.071 DOI: https://doi.org/10.1016/j.biomaterials.2005.01.071

Caridade SG, da Silva RMP, Reis RL, Mano JF. Effect of solvent-dependent viscoelastic properties of chitosan membranes on the permeation of 2-phenylethanol. Carbohydr Polym 2009; 75: 651-9. http://dx.doi.org/10.1016/j.carbpol.2008.09.011 DOI: https://doi.org/10.1016/j.carbpol.2008.09.011

Suh J-KF, Matthew HWT. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials 2000; 21: 2589-98. http://dx.doi.org/10.1016/S0142-9612(00)00126-5 DOI: https://doi.org/10.1016/S0142-9612(00)00126-5

Adekogbe I, Ghanem A. Fabrication and characterization of DTBP-crosslinked chitosan scaffolds for skin tissue engineering. Biomaterials 2005; 26: 7241-50. http://dx.doi.org/10.1016/j.biomaterials.2005.05.043 DOI: https://doi.org/10.1016/j.biomaterials.2005.05.043

Hoffmann B, Seitz D, Mencke A, Kokott A, Ziegler G. Glutaraldehyde and oxidised dextran as crosslinker reagents for chitosan-based scaffolds for cartilage tissue engineering. J Mater Sci Mater Med 2009; 20: 1495-503. http://dx.doi.org/10.1007/s10856-009-3707-3 DOI: https://doi.org/10.1007/s10856-009-3707-3

Kong L, Ao Q, Wang A, et al. Preparation and characterization of a multilayer biomimetic scaffold for bone tissue engineering. J Biomater App 2007; 22: 223-9. http://dx.doi.org/10.1177/0885328206073706 DOI: https://doi.org/10.1177/0885328206073706

van Blitterswijk C, Thomsen P, Lindahl A, et al., editors. Controlled release strategies in tissue engineering. London: Academmic Press; 2008.

Abdel-Fattah WI, Jiang T, El-Bassyouni GET, Laurencin CT. Synthesis, characterization of chitosans and fabrication of sintered chitosan microsphere matrices for bone tissue engineering. Acta Biomater 2007; 3: 503-14. http://dx.doi.org/10.1016/j.actbio.2006.12.004 DOI: https://doi.org/10.1016/j.actbio.2006.12.004

Funakoshi T, Majima T, Iwasaki N, et al. Application of tissue engineering techniques for rotator cuff regeneration using a chitosan-based hyaluronan hybrid fiber scaffold. Am J Sports Med 2005; 33: 1193-201. http://dx.doi.org/10.1177/0363546504272689 DOI: https://doi.org/10.1177/0363546504272689

Hong Y, Gong YH, Gao CY, Shen JC. Collagen-coated polylactide microcarriers/chitosan hydrogel composite: injectable scaffold for cartilage regeneration. J Biomed Mater Res A 2008; 85: 628-37. http://dx.doi.org/10.1002/jbm.a.31603 DOI: https://doi.org/10.1002/jbm.a.31603

Park KM, Joung YK, Park KD, Lee SY, Lee MC. RGD-conjugated chitosan-Pluronic hydrogels as a cell supported scaffold for articular cartilage regeneration. Macromol Res 2008; 16: 517-23. http://dx.doi.org/10.1007/BF03218553 DOI: https://doi.org/10.1007/BF03218553

Sahoo S, Cho-Hong JG, Siew-Lok T. Development of hybrid polymer scaffolds for potential applications in ligament and tendon tissue engineering. Biomed Mater 2007; 2: 169-73. http://dx.doi.org/10.1088/1748-6041/2/3/001 DOI: https://doi.org/10.1088/1748-6041/2/3/001

Lawrence BD, Marchant JK, Pindrus MA, Omenetto FG, Kaplan DL. Silk film biomaterials for cornea tissue engineering. Biomaterials 2009; 30: 1299-308. http://dx.doi.org/10.1016/j.biomaterials.2008.11.018 DOI: https://doi.org/10.1016/j.biomaterials.2008.11.018

Vrana NE, Elsheikh A, Builles N, Damour O, Hasirci V. Effect of human corneal keratocytes and retinal pigment epithelial cells on the mechanical properties of micropatterned collagen films. Biomaterials 2007; 28: 4303-10. http://dx.doi.org/10.1016/j.biomaterials.2007.06.013 DOI: https://doi.org/10.1016/j.biomaterials.2007.06.013

Yokoya S, Mochizuki Y, Nagata Y, Deie M, Ochi M. Tendon-bone insertion repair and regeneration using polyglycolic acid sheet in the rabbit rotator cuff injury model. Am J Sports Med 2008; 36: 1298-309. http://dx.doi.org/10.1177/0363546508314416 DOI: https://doi.org/10.1177/0363546508314416

McHale MK, Setton LA, Chilkoti A. Synthesis and in vitro evaluation of enzymatically cross-linked elastin-like polypeptide gels for cartilaginous tissue repair. In: van Blitterswijk C, Thomsen P, Lindahl A, et al., editors. Tissue Engineering. 112005. p. 1768-79. DOI: https://doi.org/10.1089/ten.2005.11.1768

Beachley V, Wen XJ. Fabrication of nanofiber reinforced protein structures for tissue engineering. Mater Sci Eng C 2009; 29: 2448-53. http://dx.doi.org/10.1016/j.msec.2009.07.008 DOI: https://doi.org/10.1016/j.msec.2009.07.008

Chan BP, So KF. Photochemical crosslinking improves the physicochemical properties of collagen scaffolds. J Biomed Mater Res A 2005; 75: 689-701. http://dx.doi.org/10.1002/jbm.a.30469 DOI: https://doi.org/10.1002/jbm.a.30469

Song JH, Kim HE, Kim HW. Collagen-apatite nanocomposite membranes for guided bone regeneration. J Biomed Mater Res B 2007; 83: 248-57. http://dx.doi.org/10.1002/jbm.b.30790 DOI: https://doi.org/10.1002/jbm.b.30790

Susilo ME, Roeder BA, Voytik-Harbin SL, Kokini K, Nauman EA. Development of a three-dimensional unit cell to model the micromechanical response of a collagen-based extracellular matrix. Acta Biomater 2010; 6: 1471-86. http://dx.doi.org/10.1016/j.actbio.2009.11.014 DOI: https://doi.org/10.1016/j.actbio.2009.11.014

Xu CC, Chan RW, Tirunagari N. A biodegradable, acellular xenogeneic scaffold for regeneration of the vocal fold lamina propria. In: van Blitterswijk C, Thomsen P, Lindahl A, et al., editors. Tissue Engineering. 132007. p. 551-66. DOI: https://doi.org/10.1089/ten.2006.0169

Slovikova A, Vojtova L, Jancar J. Preparation and modification of collagen-based porous scaffold for tissue engineering. Chem Papers 2008; 62: 417-22. http://dx.doi.org/10.2478/s11696-008-0045-8 DOI: https://doi.org/10.2478/s11696-008-0045-8

Liu WG, Deng C, McLaughlin CR, et al. Collagen-phosphorylcholine interpenetrating network hydrogels as corneal substitutes. Biomaterials 2009; 30: 1551-9. http://dx.doi.org/10.1016/j.biomaterials.2008.11.022 DOI: https://doi.org/10.1016/j.biomaterials.2008.11.022

Ahearne M, Yang Y, Then KY, Liu KK. Non-destructive mechanical characterisation of UVA/riboflavin crosslinked collagen hydrogels. Br J Ophthalmol 2008; 92: 268-71. http://dx.doi.org/10.1136/bjo.2007.130104 DOI: https://doi.org/10.1136/bjo.2007.130104

Brigham MD, Bick A, Lo E, Bendali A, Burdick JA, Khademhosseini A. Mechanically robust and bioadhesive collagen and photocrosslinkable hyaluronic acid semi-interpenetrating networks. Tissue Eng Part A 2009; 15: 1645-53. http://dx.doi.org/10.1089/ten.tea.2008.0441 DOI: https://doi.org/10.1089/ten.tea.2008.0441

Tan RW, Niu XF, Gan SL, Feng QL. Preparation and characterization of an injectable composite. J Mater Sci Mater Med 2009; 20: 1245-53. http://dx.doi.org/10.1007/s10856-009-3692-6 DOI: https://doi.org/10.1007/s10856-009-3692-6

Ng KW, Saliman JD, Lin EY, et al. Culture duration modulates collagen hydrolysate-induced tissue remodeling in chondrocyte-seeded agarose hydrogels. Ann Biomed Eng 2007; 35: 1914-23. http://dx.doi.org/10.1007/s10439-007-9373-z DOI: https://doi.org/10.1007/s10439-007-9373-z

Sosnik A, Sefton MV. Methylation of poloxamine for enhanced cell adhesion. Biomacromolecules 2006; 7: 331-8. http://dx.doi.org/10.1021/bm050693h DOI: https://doi.org/10.1021/bm050693h

Lv Q, Hu K, Feng Q, Cui F. Fibroin/collagen hybrid hydrogels with crosslinking method: Preparation, properties, and cytocompatibility. J Biomed Mater Res A 2008; 84: 198-207. http://dx.doi.org/10.1002/jbm.a.31366 DOI: https://doi.org/10.1002/jbm.a.31366

Sosnik A, Sefton MV. Semi-synthetic collagen/poloxamine matrices for tissue engineering. Biomaterials 2005; 26: 7425-35. http://dx.doi.org/10.1016/j.biomaterials.2005.05.086 DOI: https://doi.org/10.1016/j.biomaterials.2005.05.086

Suri S, Schmidt CE. Photopatterned collagen-hyaluronic acid interpenetrating polymer network hydrogels. Acta Biomater 2009; 5: 2385-97. http://dx.doi.org/10.1016/j.actbio.2009.05.004 DOI: https://doi.org/10.1016/j.actbio.2009.05.004

Kundu J, Dewan M, Ghoshal S, Kundu SC. Mulberry non-engineered silk gland protein vis-a-vis silk cocoon protein engineered by silkworms as biomaterial matrices. J Mater Sci Mater Med 2008; 19: 2679-89. http://dx.doi.org/10.1007/s10856-008-3398-1 DOI: https://doi.org/10.1007/s10856-008-3398-1

Zhang XH, Reagan MR, Kaplan DL. Electrospun silk biomaterial scaffolds for regenerative medicine. Adv Drug Deliv Rev 2009; 61: 988-1006. http://dx.doi.org/10.1016/j.addr.2009.07.005 DOI: https://doi.org/10.1016/j.addr.2009.07.005

She ZD, Jin CR, Huang Z, Zhang BF, Feng QL, Xu YX. Silk fibroin/chitosan scaffold: preparation, characterization, and culture with HepG2 cell. J Mater Sci Mater Med 2008; 19: 3545-53. http://dx.doi.org/10.1007/s10856-008-3526-y DOI: https://doi.org/10.1007/s10856-008-3526-y

Mandal BB, Kapoor S, Kundu SC. Silk fibroin/polyacrylamide Semi-interpenetrating network hydrogels for controlled drug release. Biomaterials 2009; 30: 2826-36. http://dx.doi.org/10.1016/j.biomaterials.2009.01.040 DOI: https://doi.org/10.1016/j.biomaterials.2009.01.040

Rammensee S, Huemmerich D, Hermanson KD, Scheibel T, Bausch AR. Rheological characterization of hydrogels formed by recombinantly produced spider silk. App Physics A 2006; 82: 261-4. http://dx.doi.org/10.1007/s00339-005-3431-x DOI: https://doi.org/10.1007/s00339-005-3431-x

Cheung HY, Lau KT, Tao XM, Hui D. A potential material for tissue engineering: Silkworm silk/PLA biocomposite. Compos Part B Eng 2008; 39: 1026-33. http://dx.doi.org/10.1016/j.compositesb.2007.11.009 DOI: https://doi.org/10.1016/j.compositesb.2007.11.009

Chew SY, Hufnagel TC, Lim CT, Leong KW. Mechanical properties of single electrospun drug-encapsulated nanofibres. Nanotechnol 2006; 17: 3880-91. http://dx.doi.org/10.1088/0957-4484/17/15/045 DOI: https://doi.org/10.1088/0957-4484/17/15/045

Chiono V, Ciardelli G, Vozzi G, et al. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(epsilon-caprolactone) blends for tissue engineering applications in the form of hollow fibers. J Biomed Mater Res A 2008; 85: 938-53. http://dx.doi.org/10.1002/jbm.a.31513 DOI: https://doi.org/10.1002/jbm.a.31513

Chiono V, Vozzi G, D'Acunto M, et al. Characterisation of blends between poly(epsilon-caprolactone) and polysaccharides for tissue engineering applications. Mater Sci Eng C 2009; 29: 2174-87. http://dx.doi.org/10.1016/j.msec.2009.04.020 DOI: https://doi.org/10.1016/j.msec.2009.04.020

Cho SW, Jeon O, Kim JE, et al. Preliminary experience with tissue engineering of a venous vascular patch by using bone marrow-derived cells and a hybrid biodegradable polymer scaffold. J Vasc Surg 2006; 44: 1329-40. http://dx.doi.org/10.1016/j.jvs.2006.07.032 DOI: https://doi.org/10.1016/j.jvs.2006.07.032

Del Gaudio C, Bianco A, Folin M, Baiguera S, Grigioni M. Structural characterization and cell response evaluation of electrospun PCL membranes: Micrometric vs. submicrometric fibers. J Biomed Mater Res A 2009; 89: 1028-39. http://dx.doi.org/10.1002/jbm.a.32048 DOI: https://doi.org/10.1002/jbm.a.32048

Duling RR, Dupaix RB, Katsube N, Lannutti J. Mechanical characterization of electrospun polycaprolactone (PCL): A potential scaffold for tissue engineering. J Biomech Eng 2008; 130: 011006. http://dx.doi.org/10.1115/1.2838033 DOI: https://doi.org/10.1115/1.2838033

Fabbri P, Bondioli F, Messori M, Bartoli C, Dinucci D, Chiellini F. Porous scaffolds of polycaprolactone reinforced with in situ generated hydroxyapatite for bone tissue engineering. J Mater Sci Mater Med 2010; 21: 343-51. http://dx.doi.org/10.1007/s10856-009-3839-5 DOI: https://doi.org/10.1007/s10856-009-3839-5

Gaumer J, Prasad A, Lee D, Lannutti J. Structure-function relationships and source-to-ground distance in electrospun polycaprolactone. Acta Biomater 2009; 5: 1552-61. http://dx.doi.org/10.1016/j.actbio.2009.01.021 DOI: https://doi.org/10.1016/j.actbio.2009.01.021

Ghasemi-Mobarakeh L, Prabhakaran MP, Morshed M, Nasr-Esfahani MH, Ramakrishna S. Electrospun poly(epsilon-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering. Biomaterials 2008; 29: 4532-9. http://dx.doi.org/10.1016/j.biomaterials.2008.08.007 DOI: https://doi.org/10.1016/j.biomaterials.2008.08.007

Jung Y, Kim SH, You HJ, Kim YH, Min BG. Application of an elastic biodegradable poly(L-lactide-co-epsilon-caprolactone) scaffold for cartilage tissue regeneration. J Biomater Sci Polym Edition 2008; 19: 1073-85. http://dx.doi.org/10.1163/156856208784909336 DOI: https://doi.org/10.1163/156856208784909336

Kotela I, Podporska J, Soltysiak E, Konsztowicz KJ, Blazewicz M. Polymer nanocomposites for bone tissue substitutes. Ceram Int 2009; 35: 2475-80. http://dx.doi.org/10.1016/j.ceramint.2009.02.016 DOI: https://doi.org/10.1016/j.ceramint.2009.02.016

Raghunath J, Georgiou G, Armitage D, et al. Degradation studies on biodegradable nanocomposite based on polycaprolactone/polycarbonate (80:20%) polyhedral oligomeric silsesquioxane. J Biomed Mater Res A 2009; 91: 834-44. http://dx.doi.org/10.1002/jbm.a.32335 DOI: https://doi.org/10.1002/jbm.a.32335

Vaquette C, Frochot C, Rahouadj R, Muller S, Wang X. Mechanical and biological characterization of a porous poly-L-lactic acid-co-epsilon-caprolactone scaffold for tissue engineering. Soft Mater 2008; 6: 25-33. http://dx.doi.org/10.1080/15394450801887109 DOI: https://doi.org/10.1080/15394450801887109

Venugopal J, Zhang YZ, Ramakrishna S. Fabrication of modified and functionalized polycaprolactone nanofibre scaffolds for vascular tissue engineering. Nanotechnol 2005; 16: 2138-42. http://dx.doi.org/10.1088/0957-4484/16/10/028 DOI: https://doi.org/10.1088/0957-4484/16/10/028

Yeh CC, Li YT, Chiang PH, Huang CH, Wang YW, Chang HI. Characterizing microporous PCL matrices for application of tissue engineering. J Med Biol Eng 2009; 29: 92-7.

Gomes ME, Azevedo HS, Moreira AR, Ella V, Kellomaki M, Reis RL. Starch-poly(epsilon-caprolactone) and starch-poly(lactic acid) fibre-mesh scaffolds for bone tissue engineering applications: structure, mechanical properties and degradation behaviour. J Tissue Eng Regen Med 2008; 2: 243-52. http://dx.doi.org/10.1002/term.89 DOI: https://doi.org/10.1002/term.89

Gualandi C, White LJ, Chen L, et al. Scaffold for tissue engineering fabricated by non-isothermal supercritical carbon dioxide foaming of a highly crystalline polyester. Acta Biomater 2010; 6: 130-6. http://dx.doi.org/10.1016/j.actbio.2009.07.020 DOI: https://doi.org/10.1016/j.actbio.2009.07.020

Guarino V, Ambrosio L. The synergic effect of polylactide fiber and calcium phosphate particle reinforcement in poly epsilon-caprolactone-based composite scaffolds. Acta Biomater 2008; 4: 1778-87. http://dx.doi.org/10.1016/j.actbio.2008.05.013 DOI: https://doi.org/10.1016/j.actbio.2008.05.013

Kim SH, Kim BS. Effect of unintended pores on vascular scaffold fabrication. Tissue Eng Regen Med 2008; 5: 594-9.

Lebourg M, Anton JS, Ribelles JLG. Porous membranes of PLLA-PCL blend for tissue engineering applications. Eur Polym J 2008; 44: 2207-18. http://dx.doi.org/10.1016/j.eurpolymj.2008.04.033 DOI: https://doi.org/10.1016/j.eurpolymj.2008.04.033

Meretoja VV, Helminen AO, Korventausta JJ, Haapa-aho V, Seppala JV, Narhi TO. Crosslinked poly(epsilon-caprolactone/D,L-lactide)/bioactive glass composite scaffolds for bone tissue engineering. J Biomed Mater Res A 2006; 77: 261-8. http://dx.doi.org/10.1002/jbm.a.30630 DOI: https://doi.org/10.1002/jbm.a.30630

Russias J, Saiz E, Deville S, et al. Fabrication and in vitro characterization of three-dimensional organic/inorganic scaffolds by robocasting. J Biomed Mater Res A 2007; 83: 434-45. http://dx.doi.org/10.1002/jbm.a.31237 DOI: https://doi.org/10.1002/jbm.a.31237

Williams JM, Adewunmi A, Schek RM, et al. Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. Biomaterials 2005; 26: 4817-27. http://dx.doi.org/10.1016/j.biomaterials.2004.11.057 DOI: https://doi.org/10.1016/j.biomaterials.2004.11.057

Atzet S, Curtin S, Trinh P, Bryant S, Ratner B. Degradable Poly(2-hydroxyethyl methacrylate)-co-polycaprolactone Hydrogels for Tissue Engineering Scaffolds. Biomacromolecules 2008; 9: 3370-7. http://dx.doi.org/10.1021/bm800686h DOI: https://doi.org/10.1021/bm800686h

Baker BM, Gee AO, Metter RB, et al. The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. Biomaterials 2008; 29: 2348-58. http://dx.doi.org/10.1016/j.biomaterials.2008.01.032 DOI: https://doi.org/10.1016/j.biomaterials.2008.01.032

Causa F, Netti PA, Ambrosio L, et al. Poly-epsilon-caprolactone/hydroxyapatite composites for bone regeneration: in vitro characterization and human osteoblast response. J Biomed Mater Res A 2006; 76: 151-62. http://dx.doi.org/10.1002/jbm.a.30528 DOI: https://doi.org/10.1002/jbm.a.30528

Ang KC, Leong KF, Chua CK, Chandrasekaran M. Compressive properties and degradability of poly(epsilon-caprolatone)/hydroxyapatite composites under accelerated hydrolytic degradation. J Biomed Mater Res A 2007; 80: 655-60. http://dx.doi.org/10.1002/jbm.a.30996 DOI: https://doi.org/10.1002/jbm.a.30996

Mondrinos MJ, Dembzynski R, Lu L, et al. Porogen-based solid freeform fabrication of polycaprolactone-calcium phosphate scaffolds for tissue engineering. Biomaterials 2006; 27: 4399-408. http://dx.doi.org/10.1016/j.biomaterials.2006.03.049 DOI: https://doi.org/10.1016/j.biomaterials.2006.03.049

Fu SZ, Gun G, Gong CY, et al. Injectable biodegradable thermosensitive hydrogel composite for orthopedic tissue engineering. 1. preparation and characterization of nanohydroxyapatite/poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) hydrogel nanocomposites. J Phys Chem B 2009; 113: 16518-25. http://dx.doi.org/10.1021/jp907974d DOI: https://doi.org/10.1021/jp907974d

Zhao S, Lee J. Supramolecular hydrogels instantaneously formed by inclusion complexation between amphiphilic oligomers and alpha-cyclodextrins. Macromol Res 2009; 17: 156-62. http://dx.doi.org/10.1007/BF03218672 DOI: https://doi.org/10.1007/BF03218672

Cascone MG, Barbani N, Cristallini C, Giusti P, Ciardelli G, Lazzeri L. Bioartificial polymeric materials based on polysaccharides. J Biomater Sci Polym Edition 2001; 12: 267-81. http://dx.doi.org/10.1163/156856201750180807 DOI: https://doi.org/10.1163/156856201750180807

Ma G, Yang D, Su D, Mu X, Kennedy JF, Nie J. Preparation and properties of water-soluble chitosan and polyvinyl alcohol blend films as potential bone tissue engineering matrix. Polym Adv Tech 2010; 21: 189-95. DOI: https://doi.org/10.1002/pat.1415

Pazos V, Mongrain R, Tardif JC. Polyvinyl alcohol cryogel: optimizing the parameters of cryogenic treatment using hyperelastic models. J Mech Behav Biomed Mater 2009; 2: 542-9. http://dx.doi.org/10.1016/j.jmbbm.2009.01.003 DOI: https://doi.org/10.1016/j.jmbbm.2009.01.003

Lee SY, Pereira BP, Yusof N, et al. Unconfined compression properties of a porous poly(vinyl alcohol)-chitosan-based hydrogel after hydration. Acta Biomater 2009; 5: 1919-25. http://dx.doi.org/10.1016/j.actbio.2009.02.014 DOI: https://doi.org/10.1016/j.actbio.2009.02.014

Brandl FP, Seitz AK, Teﬂmar JrKV, Blunk T, Göpferich AM. Enzymatically degradable poly(ethylene glycol) based hydrogels for adipose tissue engineering. Biomaterials 2010; 31: 3957-66. http://dx.doi.org/10.1016/j.biomaterials.2010.01.128 DOI: https://doi.org/10.1016/j.biomaterials.2010.01.128

Patel PN, Smith CK, Jr. CWP. Rheological and recovery properties of poly(ethylene glycol) diacrylate hydrogels and human adipose tissue. J Biomed Mater Res A 2005; 73: 313-9. http://dx.doi.org/10.1002/jbm.a.30291 DOI: https://doi.org/10.1002/jbm.a.30291

Lutolf MP, Hubbell JA. Synthesis and physicochemical characterization of end-linked poly(ethylene glycol)-co-peptide hydrogels formed by Michael-type addition. Biomacromolecules 2003; 4: 713-22. http://dx.doi.org/10.1021/bm025744e DOI: https://doi.org/10.1021/bm025744e

Rice MA, Waters KR, Anseth KS. Ultrasound monitoring of cartilaginous matrix evolution in degradable PEG hydrogels. Acta Biomater 2009; 5: 152-61. http://dx.doi.org/10.1016/j.actbio.2008.07.036 DOI: https://doi.org/10.1016/j.actbio.2008.07.036

Vermonden T, Fedorovich NE, van Geemen D, et al. Photopolymerized thermosensitive hydrogels: synthesis, degradation, and cytocompatibility. Biomacromolecules 2008; 9: 919-26. http://dx.doi.org/10.1021/bm7013075 DOI: https://doi.org/10.1021/bm7013075

Kavlock KD, Pechar TW, Hollinger JO, Guelcher SA, Goldstein AS. Synthesis and characterization of segmented poly(esterurethane urea) elastomers for bone tissue engineering. Acta Biomater 2007; 3: 475-84. http://dx.doi.org/10.1016/j.actbio.2007.02.001 DOI: https://doi.org/10.1016/j.actbio.2007.02.001

Zhang CH, Wen XJ, Vyavahare NR, Boland T. Synthesis and characterization of biodegradable elastomeric polyurethane scaffolds fabricated by the inkjet technique. Biomaterials 2008; 29: 3781-91. http://dx.doi.org/10.1016/j.biomaterials.2008.06.009 DOI: https://doi.org/10.1016/j.biomaterials.2008.06.009

Scott ON, Begley MR, Komaragiri U, Mackin TJ. Indentation of freestanding circular elastomer films using spherical indenters. Acta Mater 2004; 52: 4877-85. http://dx.doi.org/10.1016/j.actamat.2004.06.043 DOI: https://doi.org/10.1016/j.actamat.2004.06.043

Ju B-F, Wan K-T, Liu K-K. Indentation of a square elastomeric thin film by a flat-ended cylindrical punch in the presence of long-range intersurface forces. J Appl Phys 2004; 96: 6159-63. http://dx.doi.org/10.1063/1.1812822 DOI: https://doi.org/10.1063/1.1812822

Liu KF, Van Landingham MR, Ovaert TC. Mechanical characterization of soft viscoelastic gels via indentation and optimization-based inverse finite element analysis. J Mech Behav Biomed Mater 2009; 2: 355-63. http://dx.doi.org/10.1016/j.jmbbm.2008.12.001 DOI: https://doi.org/10.1016/j.jmbbm.2008.12.001

Lanza RP, Langer R, Vacanti J, editors. Principles of Tissue Engineering. 2nd ed. San Diego: Academic Press; 2000.

Raghavan D, Kropp BP, Lin H-K, Zhang Y, Cowan R, Madihally SV. Physical characteristics of small intestinal submucosa scaffolds are location-dependent. J Biomed Mater Res A 2005; 73: 90-6. http://dx.doi.org/10.1002/jbm.a.30268 DOI: https://doi.org/10.1002/jbm.a.30268

Fisher JP, Mikos AG, Bronzino JD, editors. Tissue Engineering. Boca Raton: CRC Press; 2007.

Peppas NA, Merrill EW. Crosslinked poly(vinyl alcohol) hydrogels as swollen elastic networks. J Appl Polym Sci 1977; 21: 1763-70. http://dx.doi.org/10.1002/app.1977.070210704 DOI: https://doi.org/10.1002/app.1977.070210704

Flory P. Principles of Polymer Chemistry. Ithaca, NY: Cornell University Press; 1953.