(594f) Engineering Bioactive Hydrogels for Vascularization

Bioactive hydrogels can be precisely tailored for vascular therapeutic purposes. To this end, we have developed a dextran-based hydrogel with tunable properties suitable for promoting vascularization in vivo. In our initial studies, the dextran polymer backbone was modified with four different functional groups: allyl isocyanate (AI), ethylamine (AE), chloroacetic acid (AC) and maleic anhydride (AM). The modified dextran macromers were then incorporated with polyethylene glycol diacrylate (PEGDA) to prepare a novel biodegradable dextran-based hydrogel. Physical and biological properties - such as swelling, degradation rate, in vitro and in vivo biocompatibility, and vascular endothelial growth factor (VEGF) release - were assessed on all forms of modified dextran hydrogels. From these studies, it was demonstrated that Dex-AE/PEGDA hydrogels exhibited improved biocompatibility and release properties compared to the other dextran-based hydrogels, but slower degradation and limited vascular ingrowth in vivo. In order to improve the in vivo properties of the Dex-AE/PEGDA hydrogel, we further modified its degree of substitution and crosslinking density. With these modifications, the new Dex-AE/PEGDA hydrogel was softer and exhibited faster growth factor release. To evaluate Dex-AE/PEGDA hydrogels in the context of vascular regeneration, both VEGF-encapsulated hydrogels and hydrogels lacking growth factor were subcutaneously transplanted into rats. Histological analysis indicated that the presence of VEGF favored tissue ingrowth and induced faster hydrogel degradation. Furthermore, the VEGF-encapsulated hydrogel recruited more blood vessel ingrowth than hydrogels without VEGF. These results implicate dextran-based hydrogels as a potent scaffold for vascular regeneration.