(489e) Engineering Bioactive Hydrogels for Treating Full Thickness Dermal Wounds

Burns, a dermal wound affecting millions, often heals as fibrous scar tissue.  As such, tissue engineers seek to develop systems that will heal the wound with skin regeneration rather than with scarring. Hydrogel scaffolds are similar to natural extracellular matrices and can be precisely tailored for therapeutic purposes. We have utilized two types of bioactive polysaccharide hydrogels with tunable properties suitable for promoting vascularization and healing in treating full thickness dermal wounds. Dextran polymer is modified with functional ethylamine groups (AE) designed to promote interactions with surrounding host tissue.   Hyaluronic acid (HA) hydrogel is modified with binding adhesive domain (RGD) and matrix metallopeptidase (MMP) cleavable sites, designed to induce vascular network formation in vitro from encapsulated human vascular cells.

Full thickness dermal injury is created with either punched wounds on healthy or diabetic mice or by third degree burns models. Burn wounds treated with dextran hydrogels showed enhanced re-epithelialization, hair follicle recruitment and neovasculargenesis during the healing process. Current studies extended our dextran hydrogel treatment in a porcine model for full thickness burn injury. Burn wounds in immunodeficient mice were treated with HA hydrogel containing human vascular network. Human vasculatures integrated with the host vasculature during the early stages of the healing process, only to regress during later stages of healing or when the network became stabilized with the host’s smooth muscle cells. Studies of punched wounds in immunodeficient diabetic mice are on going to determine the contribution of healthy human vascular network to the healing process. Collectively, our results have shown that the customized bioactive polysaccharide hydrogel systems provide novel platforms for treating full-thickness dermal wounds.