A newly developed chemically crosslinked dextran-poly(ethylene glycol) hydrogel for cartilage tissue engineering.

Cartilage tissue engineering, in which chondrogenic cells are combined with a scaffold, is a cell-based approach to regenerate damaged cartilage. Various scaffold materials have been investigated, among which are hydrogels. Previously, we have developed dextran-based hydrogels that form under physiological conditions via a Michael-type addition reaction. Hydrogels can be formed in situ by mixing a thiol-functionalized dextran with a tetra-acrylated star poly(ethylene glycol) solution. In this article we describe how the degradation time of dextran-poly(ethylene glycol) hydrogels can be varied from 3 to 7 weeks by changing the degree of substitution of thiol groups on dextran. The degradation times increased slightly after encapsulation of chondrocytes in the gels. The effect of the gelation reaction on cell viability and cartilage formation in the hydrogels was investigated. Chondrocytes or embryonic stem cells were mixed in the aqueous dextran solution, and we confirmed that the cells survived gelation. After a 3-week culturing period, chondrocytes and embryonic stem cell-derived embryoid bodies were still viable and both cell types produced cartilaginous tissue. Our data demonstrate the potential of dextran hydrogels for cartilage tissue engineering strategies.

[1]  J. Jansen,et al.  Effect of dual growth factor delivery on chondrogenic differentiation of rabbit marrow mesenchymal stem cells encapsulated in injectable hydrogel composites. , 2009, Journal of biomedical materials research. Part A.

[2]  J. Jukes,et al.  Potential of embryonic stem cells for in vivo bone regeneration. , 2008, Regenerative medicine.

[3]  J. Elisseeff,et al.  Derivation of Chondrogenically-Committed Cells from Human Embryonic Cells for Cartilage Tissue Regeneration , 2008, PloS one.

[4]  S. Bryant,et al.  Cell encapsulation in biodegradable hydrogels for tissue engineering applications. , 2008, Tissue engineering. Part B, Reviews.

[5]  J. Jukes,et al.  Endochondral bone tissue engineering using embryonic stem cells , 2008, Proceedings of the National Academy of Sciences.

[6]  W. Hennink,et al.  In situ gelling hydrogels for pharmaceutical and biomedical applications. , 2008, International journal of pharmaceutics.

[7]  J. Jukes,et al.  Critical Steps toward a tissue-engineered cartilage implant using embryonic stem cells. , 2008, Tissue engineering. Part A.

[8]  K. Yun,et al.  Inducing chondrogenic differentiation in injectable hydrogels embedded with rabbit chondrocytes and growth factor for neocartilage formation. , 2008, Journal of bioscience and bioengineering.

[9]  J. Feijen,et al.  Release of model proteins and basic fibroblast growth factor from in situ forming degradable dextran hydrogels. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[10]  B. Baroli,et al.  Hydrogels for tissue engineering and delivery of tissue-inducing substances. , 2007, Journal of pharmaceutical sciences.

[11]  Robert Langer,et al.  Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells , 2007, Proceedings of the National Academy of Sciences.

[12]  J. Feijen,et al.  Rapidly in situ-forming degradable hydrogels from dextran thiols through Michael addition. , 2007, Biomacromolecules.

[13]  Wim E Hennink,et al.  Biodegradable dextran hydrogels for protein delivery applications , 2007, Expert review of medical devices.

[14]  J. Feijen,et al.  Novel in situ forming, degradable dextran hydrogels by Michael addition chemistry : Synthesis, rheology, and degradation , 2007 .

[15]  P. Manson,et al.  In Vivo Chondrogenesis of Mesenchymal Stem Cells in a Photopolymerized Hydrogel , 2007, Plastic and reconstructive surgery.

[16]  Nathaniel S. Hwang,et al.  Chondrogenic differentiation of human embryonic stem cell-derived cells in arginine-glycine-aspartate-modified hydrogels. , 2006, Tissue engineering.

[17]  Zhiyuan Zhong,et al.  In-situ formation of biodegradable hydrogels by stereocomplexation of PEG-(PLLA)8 and PEG-(PDLA)8 star block copolymers. , 2006, Biomacromolecules.

[18]  Somponnat Sampattavanich,et al.  Effects of Three‐Dimensional Culture and Growth Factors on the Chondrogenic Differentiation of Murine Embryonic Stem Cells , 2006, Stem cells.

[19]  Wim E Hennink,et al.  Self-gelling hydrogels based on oppositely charged dextran microspheres. , 2005, Biomaterials.

[20]  R. Langer,et al.  Adhesion-mediated signal transduction in human articular chondrocytes: the influence of biomaterial chemistry and tenascin-C. , 2004, Experimental cell research.

[21]  S. Kawai,et al.  Chondrogenic differentiation of murine embryonic stem cells: Effects of culture conditions and dexamethasone , 2004, Journal of cellular biochemistry.

[22]  J. Hubbell,et al.  Synthesis and physicochemical characterization of end-linked poly(ethylene glycol)-co-peptide hydrogels formed by Michael-type addition. , 2003, Biomacromolecules.

[23]  P. Martens,et al.  Tailoring the degradation of hydrogels formed from multivinyl poly(ethylene glycol) and poly(vinyl alcohol) macromers for cartilage tissue engineering. , 2003, Biomacromolecules.

[24]  Kytai Truong Nguyen,et al.  Photopolymerizable hydrogels for tissue engineering applications. , 2002, Biomaterials.

[25]  J. Hubbell,et al.  Systematic modulation of Michael-type reactivity of thiols through the use of charged amino acids. , 2001, Bioconjugate chemistry.

[26]  J. Hubbell,et al.  Protein delivery from materials formed by self-selective conjugate addition reactions. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[27]  D. Mooney,et al.  Hydrogels for tissue engineering. , 2001, Chemical reviews.

[28]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[29]  P. Ma,et al.  Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: part 1. Structure, gelation rate and mechanical properties. , 2001, Biomaterials.

[30]  V. Bobić,et al.  Articular Cartilage - to Repair or not to Repair , 2000 .

[31]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[32]  H J Mankin,et al.  Articular cartilage repair and transplantation. , 1998, Arthritis and rheumatism.

[33]  A I Caplan,et al.  In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. , 1998, Experimental cell research.

[34]  C. Ohlsson,et al.  Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. , 1994, The New England journal of medicine.

[35]  A. Smith,et al.  Buffalo rat liver cells produce a diffusible activity which inhibits the differentiation of murine embryonal carcinoma and embryonic stem cells. , 1987, Developmental biology.

[36]  G. Martin,et al.  Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Kaufman,et al.  Establishment in culture of pluripotential cells from mouse embryos , 1981, Nature.

[38]  Zhiyuan Zhong,et al.  Enzyme-mediated fast in situ formation of hydrogels from dextran-tyramine conjugates. , 2007, Biomaterials.

[39]  G. Daculsi,et al.  Cartilage and bone tissue engineering using hydrogels. , 2006, Bio-medical materials and engineering.

[40]  A. Metters,et al.  Network formation and degradation behavior of hydrogels formed by Michael-type addition reactions. , 2005, Biomacromolecules.

[41]  T. Sheffield,et al.  Thermally cross-linked oligo(poly(ethylene glycol) fumarate) hydrogels support osteogenic differentiation of encapsulated marrow stromal cells in vitro. , 2004, Biomacromolecules.

[42]  C. van Nostrum,et al.  Novel crosslinking methods to design hydrogels. , 2002, Advanced drug delivery reviews.

[43]  A M Mackay,et al.  Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow. , 1998, Tissue engineering.