Development of Hydrogel Wound Dressings for Chronic Wound Healing

Chronic wounds are a growing healthcare issue afflicting over 40 million people in the United States. Despite the billions of dollars spent each year, complications from diabetic ulcers result in a large number of lower extremity amputations. Current dressings fail to address the complex nature of the wound environment and are often only able to address one aspect of wound healing providing marginal wound closure rates and resulting in treatment failure. To address the limitations of standard treatments, we have developed a biodegradable and bioactive hydrogel dressing that incorporates a novel antimicrobial agent to eliminate and prevent infection. Here, we have developed a wound healing platform that promotes wound fluid maintenance through tunable hydrogel geometries, targeted cellular interactions, and bacterial inhibition. In this work, a tunable biomaterial platform with integrin-mediated cellular interactions, controlled degradation profiles, and antimicrobial properties was developed to treat a variety of complex wound environments. Engineered Streptococcal collagen-like (Scl2) proteins were optimized with improved stability and promotion of cellular attachment. These poly(ethylene glycol)-based hydrogels were fabricated in hydrogel microspheres and 3D-printed porous hydrogel foams to develop a platform to treat complex wound environments. Swelling ratio and rate were investigated to determine water uptake and equilibrium swelling times. Furthermore, biocompatibility and biodegradation of poly(ethylene glycol)-dithiothreitol hydrogels were modulated and in vivo degradation profiles were investigated. The development of a tunable platform with rapid degradation in vivo has potential to be utilized as a resorbable dressing that eliminates inflammatory concerns due to residual dressing fragments. Finally, gallium maltolate (GaM), a novel antimicrobial agent, was incorporated into these hydrogel scaffolds and evaluated in vitro and in vivo in a splinted wound model. Release profiles, bacterial inhibition, and wound closure was investigated in these GaM loaded hydrogels. Overall, the development of this wound healing platform with conferred antimicrobial activity and tunable degradation properties resulted in an improved wound dressing system with controlled moisture balance, infection control, and potential for cell mediated wound healing. Furthermore, these technologies can be translated into other regenerative applications and scaffold geometries demonstrating the broader impacts of this wound healing platform