Hydrogel properties influence ECM production by chondrocytes photoencapsulated in poly(ethylene glycol) hydrogels.

When using hydrogel scaffolds for cartilage tissue engineering, two gel properties are particularly important: the equilibrium water content (q, equilibrium swelling ratio) and the compressive modulus, K. In this work, chondrocytes were photoencapsulated in degrading and nondegrading poly(ethylene glycol)-based hydrogels to assess extracellular matrix (ECM) formation as a function of these gel properties. In nondegrading gels, the glycosaminoglycan (GAG) content was not significantly different in gels when q was varied from 4.2 to 9.3 after 2 and 4 weeks in vitro. However, gels with a q of 9.3 allowed GAGs to diffuse throughout the gels homogenously, but a q < or = 5.2 resulted in localization of GAGs pericellularly. Interestingly, in the moderately crosslinked gels with a K of 360 kPa, an increase in type II collagen synthesis was observed compared with gels with a higher (960 kPa) and lower (30 kPa) K after 4 weeks. With the incorporation of degradable linkages into the network, gel properties with an initially high K (350 kPa) and final high q (7.9) were obtained, which allowed for increased type II collagen synthesis coupled with a homogenous distribution of GAGs. Thus, a critical balance exists between gel swelling, mechanics, and degradation in forming a functional ECM.

[1]  J. F. Woessner,et al.  The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. , 1961, Archives of biochemistry and biophysics.

[2]  V C Mow,et al.  Variations in the intrinsic mechanical properties of human articular cartilage with age, degeneration, and water content. , 1982, The Journal of bone and joint surgery. American volume.

[3]  J. Buckwalter,et al.  Structural changes during development in bovine fetal epiphyseal cartilage. , 1981, Collagen and related research.

[4]  N. Peppas Hydrogels in Medicine and Pharmacy , 1987 .

[5]  A. Grodzinsky,et al.  Fluorometric assay of DNA in cartilage explants using Hoechst 33258. , 1988, Analytical biochemistry.

[6]  N. Peppas,et al.  Correlation between mesh size and equilibrium degree of swelling of polymeric networks. , 1989, Journal of biomedical materials research.

[7]  R. Dulbecco Encyclopedia of human biology , 1991 .

[8]  I. B. Larsen,et al.  Effect of human saliva on surface degradation of composite resins. , 1991, Scandinavian journal of dental research.

[9]  R Langer,et al.  Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers. , 1993, Journal of biomedical materials research.

[10]  E. Merrill,et al.  Partitioning and diffusion of solutes in hydrogels of poly(ethylene oxide). , 1993, Biomaterials.

[11]  Jeffrey A. Hubbell,et al.  Bioerodible hydrogels based on photopolymerized poly(ethylene glycol)-co-poly(.alpha.-hydroxy acid) diacrylate macromers , 1993 .

[12]  C. Rorabeck,et al.  Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay. , 1994, The Journal of clinical investigation.

[13]  P Aebischer,et al.  Hydrogel-based three-dimensional matrix for neural cells. , 1995, Journal of biomedical materials research.

[14]  J. Kimura,et al.  Chondrocyte and chondrosarcoma cell integrins with affinity for collagen type II and their response to mechanical stress. , 1995, Experimental cell research.

[15]  G W Plant,et al.  Neural tissue engineering: from polymer to biohybrid organs. , 1996, Biomaterials.

[16]  D. R. Carter,et al.  In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure , 1996, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[17]  D J Mooney,et al.  Development of biocompatible synthetic extracellular matrices for tissue engineering. , 1998, Trends in biotechnology.

[18]  Yilin Cao,et al.  Comparative study of the use of poly(glycolic acid), calcium alginate and pluronics in the engineering of autologous porcine cartilage. , 1998, Journal of biomaterials science. Polymer edition.

[19]  J. Elisseeff,et al.  In vitro prefabrication of human cartilage shapes using fibrin glue and human chondrocytes. , 1998, Annals of Plastic Surgery.

[20]  H Planck,et al.  Cartilage reconstruction in head and neck surgery: comparison of resorbable polymer scaffolds for tissue engineering of human septal cartilage. , 1998, Journal of biomedical materials research.

[21]  H. Nötzli,et al.  Collagen fibre arrangement in the tibial plateau articular cartilage of man and other mammalian species , 1998, Journal of anatomy.

[22]  J. Elisseeff,et al.  Transdermal photopolymerization of poly(ethylene oxide)-based injectable hydrogels for tissue-engineered cartilage. , 1999, Plastic and reconstructive surgery.

[23]  S. Bryant,et al.  The effects of crosslinking density on cartilage formation in photocrosslinkable hydrogels. , 1999, Biomedical sciences instrumentation.

[24]  D L Butler,et al.  Autologous mesenchymal stem cell-mediated repair of tendon. , 1999, Tissue engineering.

[25]  M. Lafage-Proust,et al.  Effects of static or dynamic mechanical stresses on osteoblast phenotype expression in three‐dimensional contractile collagen gels , 2000, Journal of cellular biochemistry.

[26]  H J Helminen,et al.  Biomechanical and structural characteristics of canine femoral and tibial cartilage. , 1999, Journal of biomedical materials research.

[27]  J O Hollinger,et al.  Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats. , 1999, Journal of biomedical materials research.

[28]  S. Woerly,et al.  Restorative surgery of the central nervous system by means of tissue engineering using NeuroGel implants , 2000, Neurosurgical Review.

[29]  S J Bryant,et al.  Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro , 2000, Journal of biomaterials science. Polymer edition.

[30]  John F. Bolton,et al.  Chondrocyte deformation within compressed agarose constructs at the cellular and sub-cellular levels. , 2000, Journal of biomechanics.

[31]  Z. Gugala,et al.  In vitro growth and activity of primary chondrocytes on a resorbable polylactide three-dimensional scaffold. , 2000, Journal of biomedical materials research.

[32]  Kristi S. Anseth,et al.  Release Behavior of High Molecular Weight Solutes from Poly(ethylene glycol)-Based Degradable Networks , 2000 .

[33]  J. Elisseeff,et al.  Photoencapsulation of chondrocytes in poly(ethylene oxide)-based semi-interpenetrating networks. , 2000, Journal of biomedical materials research.

[34]  Jon A. Rowley,et al.  Controlling Mechanical and Swelling Properties of Alginate Hydrogels Independently by Cross-Linker Type and Cross-Linking Density , 2000 .

[35]  Kristi S. Anseth,et al.  Fundamental studies of a novel, biodegradable PEG-b-PLA hydrogel , 2000 .

[36]  Kristi S. Anseth,et al.  Verification of scaling laws for degrading PLA‐b‐PEG‐b‐PLA hydrogels , 2001 .

[37]  C. Bowman,et al.  Kinetic modeling of the effect of solvent concentration on primary cyclization during polymerization of multifunctional monomers , 2001 .

[38]  Jennifer L. West,et al.  Tethered-TGF-β increases extracellular matrix production of vascular smooth muscle cells , 2001 .

[39]  Stephanie J Bryant,et al.  Controlling the spatial distribution of ECM components in degradable PEG hydrogels for tissue engineering cartilage. , 2003, Journal of biomedical materials research. Part A.