Design of semi-degradable hydrogels based on poly(vinyl alcohol) and poly(lactic-co-glycolic acid) for cartilage tissue engineering
Kara L. Spiller
Biomaterials and Drug Delivery Laboratory, Department of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USA
School of Biomedical Engineering, Drexel University, Philadelphia, PA, USA
Search for more papers by this authorJulianne L. Holloway
Biomaterials and Drug Delivery Laboratory, Department of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USA
Search for more papers by this authorMegan E. Gribb
Biomaterials and Drug Delivery Laboratory, Department of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USA
Search for more papers by this authorCorresponding Author
Anthony M. Lowman
Biomaterials and Drug Delivery Laboratory, Department of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USA
Drexel University College of Engineering, Biomaterials and Drug Delivery Laboratory, Dept. of Chemical and Biological Engineering, Philadelphia, PA 19104, USA.Search for more papers by this authorKara L. Spiller
Biomaterials and Drug Delivery Laboratory, Department of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USA
School of Biomedical Engineering, Drexel University, Philadelphia, PA, USA
Search for more papers by this authorJulianne L. Holloway
Biomaterials and Drug Delivery Laboratory, Department of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USA
Search for more papers by this authorMegan E. Gribb
Biomaterials and Drug Delivery Laboratory, Department of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USA
Search for more papers by this authorCorresponding Author
Anthony M. Lowman
Biomaterials and Drug Delivery Laboratory, Department of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USA
Drexel University College of Engineering, Biomaterials and Drug Delivery Laboratory, Dept. of Chemical and Biological Engineering, Philadelphia, PA 19104, USA.Search for more papers by this authorAbstract
Articular cartilage damage is a persistent challenge in biomaterials and tissue engineering. Poly(vinyl alcohol) (PVA) hydrogels have shown promise as implants, but their lack of integration with surrounding cartilage prevents their utility. We sought to combine the advantages of PVA hydrogels with poly(lactic-co-glycolic acid) (PLGA) scaffolds, which have been successful in facilitating the integration of neocartilage with surrounding tissue. Through a novel double-emulsion technique, PLGA microparticles and a high level of porosity were simultaneously incorporated into PVA hydrogels. The porosity, average pore size and swelling properties of the hydrogels were controlled by varying initial processing parameters, such as the relative amounts of PLGA and solvent. Average pore sizes were in the ranged 50–100 µm. The PLGA microparticles degraded within the hydrogels over time in aqueous conditions, resulting in increases in porosity and pore size. After 4 weeks in cell culture, immature cartilage tissue filled many of the pores of the hydrogels that initially contained PLGA, and proteoglycan production was proportional to the amount of PLGA. In contrast, there was little cell attachment and no proteoglycan production in control hydrogels without PLGA. The compressive moduli of the hydrogels were similar to that of healthy cartilage and increased over time from 0.05–0.1 to 0.3–0.7 MPa. The generation of a hybrid cartilage–hydrogel construct using this technique may finally allow the integration of PVA hydrogels with surrounding cartilage. Copyright © 2010 John Wiley & Sons, Ltd.
References
- 1Benya PD, Shaffer JD. 1982; Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30(1): 215–224.
- 2Brandl F, Sommer F, Goepferich A. 2007; Rational design of hydrogels for tissue engineering: impact of physical factors on cell behavior. Biomaterials 28(2): 134–146.
- 3Bray JC, Merrill EW. 1973; Poly(vinyl alcohol) hydrogels for synthetic articular cartilage material. J Biomed Mater Res 7(5): 431–443.
- 4Broom ND, Oloyede A. 1998; The importance of physicochemical swelling in cartilage illustrated with a model hydrogel system. Biomaterials 19(13:): 1179–1188.
- 5Bryant S, Anseth K. 2002; Hydrogel properties influence ECM production by chondrocytes photoencapsulated in poly(ethylene glycol) hydrogels. J Biomed Mater Res 59: 63–72.
- 6Bryant SJ, Davis-Arehart KA, Luo N, et al. 2004; Synthesis and characterization of photopolymerized multifunctional hydrogels: water-soluble poly(vinyl alcohol) and chondroitin sulfate macromers for chondrocyte encapsulation. Macromolecules 37: 6726–6733.
- 7Buckwalter JA, Mankin H. 1997; Articular cartilage. Part II: degeneration and osteoarthritis, repair, regeneration, and transplantation. J Bone Joint Surg 79A(4): 612–632.
- 8Charlton DC, Peterson MG, Spiller K, et al. 2008; Semi-degradable scaffold for articular cartilage replacement. Tissue Eng A 14(1): 207–213.
- 9Cushing MC, Anseth KS. 2007; Materials science. Hydrogel cell cultures. Science 316(5828): 1133–1134.
- 10Dar A, Shachar M, Leor J, et al. 2002; Optimization of cardiac cell seeding and distribution in 3D porous alginate scaffolds. Biotechnol Bioeng 80(3): 305–312.
- 11Drury JL, Mooney DJ. 2003; Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 24(24): 4337–4351.
- 12Elisseeff JH, Ruffner M, Kim TG, et al. 2005; Cellular photoencapsulation in hydrogels. In Culture of Cells for Tissue Engineering, G Vunjak-Novakovic, RI Freshney (eds). Wiley: New York; 213–239.
10.1002/0471741817.ch9 Google Scholar
- 13Frenkel S, Cesare PD. 2004a; Scaffolds for articular cartilage repair. Ann Biomed Eng 32(1): 26–34.
- 14Frenkel SR, Cesare PED. 2004b; Scaffolds for articular cartilage repair. Ann Biomed Eng 32(1): 26–34.
- 15Genes NG, Rowley JA, Mooney DJ, et al. 2004; Effect of substrate mechanics on chondrocyte adhesion to modified alginate surfaces. Arch Biochem Biophys 422(2): 161–167.
- 16Gong Y, He L, Zhou Q, et al. 2007; Hydrogel-filled polylactide porous scaffolds for cartilage tissue engineering. J Biomed Mater Res B Appl Biomater 82B: 192–204.
- 17Grant C, Twigg P, Egan A, et al. 2006; Poly(vinyl alcohol) hydrogel as a biocompatible viscoelastic mimetic for articular cartilage. Biotechnol Progr 22(5): 1400–1406.
- 18Guo T, Yang T, Xiao J, et al. 2008; Repair of articular cartilage and subchondral defects with a new type biological composite material polyvinyl alcohol/nano-hydroxyapatite and polyamide 66. J Clin Rehab Tissue Eng Res 12(14): 2623–2627.
- 19Hassan CM, Peppas N. 2000; Modeling of crystal dissolution of poly(vinyl alcohol) gels produced by freezing/thawing processes. Polymer 41: 6729–6739.
- 20Hunter CJ, Levenston ME. 2004; Maturation and integration of tissue-engineered cartilages within an in vitro defect repair model. Tissue Eng 10(5–6): 736–746.
- 21Joshi A, Fussell G, Thomas J, et al. 2006; Functional compressive mechanics of a PVA/PVP nucleus pulposus replacement. Biomaterials 27(2): 176–184.
- 22Katta JK, Marcolongo M, Lowman A, et al. 2007; Friction and wear behavior of poly(vinyl alcohol)/poly(vinyl pyrrolidone) hydrogels for articular cartilage replacement. J Biomed Mater Res A 83(2): 471–479.
- 23Kim YJ, Sah RL, Doong JY, et al. 1988; Fluorometric assay of DNA in cartilage explants using Hoechst 33258. Anal Biochem 174(1): 168–176.
- 24Kobayashi M, Oka M. 2004; Characterization of a polyvinyl alcohol–hydrogel artificial articular cartilage prepared by injection molding. J Biomater Sci 15(6): 741–751.
- 25Korhonen R, Laasanen M, Toyras J, et al. 2002; Comparison of the equilibrium response of articular cartilage in unconfined compression, confined compression, and indentation. J Biomech 35: 903–909.
- 26Lammi MJ. 2004; Current perspectives on cartilage and chondrocyte mechanobiology. Biorheology 41(3–4): 593–596.
- 27Lee SY, Pereira BP, Yusof N, et al. 2009; Unconfined compression properties of a porous poly(vinyl alcohol)-chitosan-based hydrogel after hydration. Acta Biomater 5(6): 1919–1925.
- 28Liu X, Fussell G, Marcolongo M, et al. 2009; Characterization of associating hydrogels of poly(vinyl alcohol) and poly(vinyl pyrrolidone). J Appl Polym Sci 112: 541–549.
- 29Lowman A, Peppas N. 1999; Hydrogels. In Encyclopedia of Controlled Drug Delivery, E Mathiowitz (ed.). Wiley: New York.
- 30Maher SA, Doty SB, Torzilli PA, et al. 2007; Nondegradable hydrogels for the treatment of focal cartilage defects. J Biomed Mater Res A 83(1): 145–155.
- 31Mallapragada SK, Peppas N. 1996; Dissolution mechanism of semicrystalline poly(vinyl alcohol) in water. J Polym Sci B Polym Phys 34: 1339–1346.
- 32Martens PJ, Bryant SJ, Anseth KS. 2003; Tailoring the degradation of hydrogels formed from multivinyl poly(ethylene glycol) and poly(vinyl alcohol) macromers for cartilage tissue engineering. Biomacromolecules 4(2): 283–292.
- 33Martin JA, Buckwalter JA. 1998; Effects of fibronectin on articular cartilage chondrocyte proteoglycan synthesis and response to insulin-like growth factor-I. J Orthop Res 16(6): 752–757.
- 34Martin JA, Buckwalter JA. 2002; Aging, articular cartilage chondrocyte senescence and osteoarthritis. Biogerontology 3(5): 257–264.
- 35Mauck RL, Soltz MA, Wang CC, et al. 2000; Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J Biomech Eng 122(3): 252–260.
- 36Mohan N, Nair PD. 2008; Polyvinyl alcohol-poly(caprolactone) semi IPN scaffold with implication for cartilage tissue engineering. J Biomed Mater Res B Appl Biomater 84(2): 584–594.
- 37Nuttelman CR, Mortisen DJ, Henry SM, et al. 2001; Attachment of fibronectin to poly(vinyl alcohol) hydrogels promotes NIH3T3 cell adhesion, proliferation, and migration. J Biomed Mater Res 57(2): 217–223.
- 38Park JS, Woo DG, Sun BK, et al. 2007; In vitro and in vivo test of PEG/PCL-based hydrogel scaffold for cell delivery application. J Control Release 124(1–2): 51–59.
- 39Passaretti D, Silverman RP, Huang W, et al. 2001; Cultured chondrocytes produce injectable tissue-engineered cartilage in hydrogel polymer. Tissue Eng 7(6): 805–815.
- 40Pennypacker JP, Hassell JR, Yamada KM, et al. 1979; The influence of an adhesive cell surface protein on chondrogenic expression in vitro. Exp Cell Res 121(2): 411–415.
- 41Peppas N. 1997; Hydrogels. In Biomaterials Science: An Introduction to Materials in Medicine, BD Ratner, AS Hoffman, FJ Schoen, JE Lemons (eds). Academic Press: San Diego, CA.
- 42Ratner BD, Hoffman AS. 1976; Synthetic hydrogels for biomedical applications. In Hydrogels for Medical and Related Applications, ACS Symposium Series, J Andrade (ed.). American Chemical Society: Washington, DC, USA; 1–36.
10.1021/bk-1976-0031.ch001 Google Scholar
- 43Silverman RP, Bonasser L, Passaretti D, et al. 2000; Adhesion of tissue-engineered cartilate to native cartilage. Plast Reconstr Surg 105(4): 1393–1398.
- 44Solchaga LA, Temenoff JS, Gao J, et al. 2005; Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds. Osteoarthr Cartilage 13(4): 297–309.
- 45Spiller KL, Laurencin SJ, Charlton D, et al. 2008; Superporous hydrogels for cartilage repair: evaluation of the morphological and mechanical properties. Acta Biomater 4(1): 17–25.
- 46Spiller KL, Laurencin SJ, Lowman AM. 2009; Characterization of the behavior of porous hydrogels in model osmotically-conditioned articular cartilage systems. J Biomed Mater Res B Appl Biomater 90(2): 752–759.
- 47Spiteri CG, Pilliar RM, Kandel RA. 2006; Substrate porosity enhances chondrocyte attachment, spreading, and cartilage tissue formation in vitro. J Biomed Mater Res A 78(4): 676–683.
- 48Stammen JA, Williams S, Ku DN, et al. 2001; Mechanical properties of a novel PVA hydrogel in shear and unconfined compression. Biomaterials 22(8): 799–806.
- 49Thomas J, Lowman A, Marcolongo M. 2003; Novel associated hydrogels for nucleus pulposus replacement. J Biomed Mater Res A 67(4): 1329–1337.
- 50Vunjak-Novakovic G, Obradovic B, Martin I, et al. 1998; Dynamic cell seeding of polymer scaffolds for cartilage tissue engineering. Biotechnol Progr 14(2): 193–202.
- 51Wang D, Williams CG, Yang F, et al. 2004; Enhancing the tissue–biomaterial interface: tissue-initiated integration of biomaterials. Adv Funct Mater 14(12): 1152–1159.
- 52Wendt D, Marsano A, Jakob M, et al. 2003; Oscillating perfusion of cell suspensions through three-dimensional scaffolds enhances cell seeding efficiency and uniformity. Biotechnol Bioeng 84(2): 205–214.
- 53Woodfield TB, Miot S, Martin I, et al. 2006; The regulation of expanded human nasal chondrocyte redifferentiation capacity by substrate composition and gas plasma surface modification. Biomaterials 27(7): 1043–1053.
- 54Yamaoka H, Asato H, Ogasawara T, et al. 2006; Cartilage tissue engineering using human auricular chondrocytes embedded in different hydrogel materials. J Biomed Mater Res A 78(1): 1–11.
- 55Zhou G, Liu W, Cui L, et al. 2006; Repair of porcine articular osteochondral defects in non-weightbearing areas with autologous bone marrow stromal cells. Tissue Eng 12(11): 3209–3221.