Synthesis of cell-adhesive dextran hydrogels and macroporous scaffolds

Dextran hydrogels have been previously investigated as drug delivery vehicles and more recently as macroporous scaffolds; however, the non-cell-adhesive nature of dextran has limited its utility for tissue engineering. To overcome this limitation, macroporous scaffolds of methacrylated dextran (Dex-MA) copolymerized with aminoethyl methacrylate (AEMA) were synthesized, thereby introducing primary amine groups for covalent immobilization of extracellular-matrix-derived peptides. The amino group density for hydrogels copolymerized with 0.5 wt% AEMA was found to be 36.1 +/- 0.4 mu mol/cm(3) by elemental analysis. To further enhance cellular interaction, poly(Dex-MA-co-AEMA) hydrogels were modified with either CRGDS or a mixture of CDPGYIGSR and CQAASIKVAV (1:1, v/v) using sulfo-(N-maleimidomethyl)cyclohexane-l-carboxylate (sulfo-SMCC). The immobilized peptide concentration was determined using amino acid analysis at: 2.6 +/- 0.9pmol/cm(3) for CRGDS-derived hydrogels and 2.2 +/- 0.3pmot/em 3 plus 1.9 +/- 0.2pmol/cm(3) for CDPGYIGSR plus CQAASIKVAV-derived hydrogels, respectively. Cellular interactions of primary embryonic chick dorsal root ganglia (DRGs) were compared on the hydrogels. Cell adhesion and neurite outgrowth on poly(Dex-MA) increased with copolymerization of AEMA and further improved with peptide modification and significantly for CDPGYIGSR/CQAASIKVAV-derived poly(Dex-MA-co-AEMA) hydrogels. Moreover, DRGs penetrated within the first 600 mu m of the scaffolds, thereby demonstrating the potential of this scaffold for guided cell and axonal regeneration in vivo. (c) 2006 Elsevier Ltd. All rights reserved.