Hyaluronic acid-based hydrogels for cartilage repair
University of Delaware
We are interested in developing hyaluronic acid (HA)- based hydrogels that can be used for cartilage repair and regeneration. To this end, nanoporous HA hydrogel particles (HGPs) with an average diameter of 6- 7 ?m were synthesized in an inverse water- in - oil emulsion system. A synthetic peptide, CK2.1, with chondro - inductive potentials, was covalently conjugated to HA HGPs via a hydrolytically degradable linker and was released from HGPs in controlled manner over 7 days. Alternatively, reductive animation reaction was employed for covalent immobilization of gelatin to HGPs (gHGPs). Separately, glycidyl methacrylate was allowed to react with HA to yield HA- glycidyl methacrylate (HAGMA) conjugates. HA- based doubly crosslinked network hydrogels (DXNs) were synthesized via UV - initiated radical crosslinking of HAGMA macromonomers in the presence of HGPs. When gHGPs were used in place of HGPs, cell- adhesive HA DXNs were obtained. Human mesenchymal stem cells (hMSCs) entrapped in HAGMA- gHGP gels were able to attach to the matrix through focal adhesion. The cell - adhesive HA DXNs induced the chondrogenic differentiation of hMSCs in MSC maintenance media, as evidenced by the exp ression of cartilage- specific matrix components (eg collagen II, aggrecan and sulfated glycosaminoglycan, sGAG). The viscoelastic properties of HA DXNs were assessed at low frequencies (<10 Hz) by a commercial rheometer and at high frequencies ( 10- 100 Hz ) using a home- built torsional wave apparatus (TWA). Compared to the cell - free DXNs, the cell/gel constructs were stiffer. The G’ value of cell- seeded HAGMA- gHGP gels were 1210±70 Pa and 1502±220 Pa at frequencies of 0.1- 10 Hz and around 50 Hz, respectively.