Alginate hydrogels as synthetic extracellular matrix materials

Alginate hydrogels are used extensively in cell encapsulation, cell transpl antation, and tissue engineering applications. Alginates possess many favor able properties required in biomaterials, but are unable to specifically in teract with mammalian cells. We have therefore covalently modified alginate polysaccharides with RGD-containing cell adhesion ligands utilizing aqueou s carbodiimide chemistry. The chemistry has been optimized and quantified w ith reaction efficiencies reaching 80% or greater. The concentration of pep tide available for reaction was then varied to create hydrogels with a rang e of ligand densities. Mouse skeletal myoblasts were cultured on alginate h ydrogel surfaces coupled with GRGDY peptides to illustrate achievement of c ellular interaction with the otherwise non-adhesive hydrogel substrate. Myo blasts adhere to GRGDY-modified alginate surfaces, proliferate, fuse into m ultinucleated myofibrils, and express heavy-chain myosin which is a differe ntiation marker for skeletal muscle. Myoblast adhesion and spreading on the se GRGDY-modified hydrogels was inhibited with soluble ligand added to the seeding medium, illustrating the specificity of adhesion to these materials . Alginate may prove to be an ideal material with which to confer specific cellular interactive properties, potentially allowing for the control of lo ng-term gene expression of cells within these matrices. (C) 1998 Elsevier S cience Ltd. All rights reserved.