A biomimetic hydrogel based on methacrylated dextran-graft-lysine and gelatin for 3D smooth muscle cell culture

Many synthetic hydrogels for cell encapsulation have hitherto been based on polyethylene glycol which is non-natural, non-biodegradable and only terminal-functionalizable, all of which are drawbacks for tissue engineering or cell delivery. The polysaccharide dextran is also highly hydrophilic but biodegradable and pendant-functionalizable and more closely resembles glycosaminoglycans to mimic the natural extracellular matrix. This study reports synthesis of a methacrylate and lysine functionalized dextran and development of hydrogel composite systems based on this material and methacrylamide modified gelatin. The mechanical stiffness and degree of swelling of the hydrogels were varied by manipulation of the degree of functionalization of dextran and gelatin and concentration/composition of precursor solution. Human umbilical artery smooth muscle cells (SMCs) were encapsulated inside hydrogels during gel hardening with photopolymerization. Rapid cell spreading, extensive cellular network formation and high SMC proliferation occurred within softer hydrogels (with shear storage moduli ranging from 898 to 3124Pa). The encapsulated SMCs appear to be relatively contractile in the initial culture than on tissue culture polystyrene dish due to physical constraint imposed by the hydrogels but they become more synthetic with time possibly due to the inability of cells to reach confluence inside these cell-mediated degradable hydrogels. From the impressive cell proliferation and network formation, these new hydrogels combining polysaccharide and protein derivatives appear to be excellent candidates for further development as bioactive scaffolds for use in vascular tissue engineering and regeneration.