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 micromol/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-1-carboxylate (sulfo-SMCC). The immobilized peptide concentration was determined using amino acid analysis at: 2.6+/-0.9 micromol/cm(3) for CRGDS-derived hydrogels and 2.2+/-0.3 micromol/cm(3) plus 1.9+/-0.2 micromol/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 microm of the scaffolds, thereby demonstrating the potential of this scaffold for guided cell and axonal regeneration in vivo.
Lévesque
Stéphane G
SG
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ont., Canada M5S 3E5.
Shoichet
Molly S
MS
D000269:Adhesives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D003911:Dextrans / Q000737:chemistry*; D005021:Ethylamines / Q000737:chemistry*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008689:Methacrylates / Q000737:chemistry*; D016501:Neurites / Q000187:drug effects; D009842:Oligopeptides / Q000737:chemistry; D016062:Porosity; D000267:Tissue Adhesions; D023822:Tissue Engineering
D000269:Adhesives; D003911:Dextrans; D005021:Ethylamines; D020100:Hydrogels; D008689:Methacrylates; D009842:Oligopeptides; C514459:aminoethyl methacrylate; C514458:methacrylated dextran