Development of Biodegradable, Peptide-Releasing Fiber Mats to Limit Burn Injury Progression

Abstract

Burns are not localized to the initial site of trauma but rather progress both horizontally and/or vertically, often converting partial-thickness burns into full-thickness burns within hours to days. Although burn care has advanced throughout the years, there is still an unmet need for treatments that can limit burn injury progression. To achieve this goal, the development of a topical, biocompatible therapy that can prevent cell death is required. A fibronectin-derived bioactive peptide (P12) has been elucidated by the Clark laboratory and shows significant promise in the treatment of burns; P12 prevented cell death in vitro and its intravenous administration limited burn progression in vivo. For localized burns (less than 20% total body surface area) in patients not requiring critical care, the topical route of delivery is more favorable due to its ease of application and localized treatment to the wound. Thus, the goal of this Dissertation research was to develop a biodegradable matrix from the latest generation of L-tyrosine-derived polycarbonate terpolymers for topical P12 delivery to localized burns. Two terpolymer compositions were chosen and electrospun to fabricate ultrafast (8 hours) and fast (4 days) P12-releasing fiber mats. Both terpolymers were fast degrading and retained less than 20% of their initial molecular weight after 7 days. However, polymer erosion and P12 release were dependent on polymer composition. P12 release was predominantly controlled by polymer erosion of ultrafast fibers, whereas the mechanism of release from fast fibers was governed by P12 diffusion. Both P12-loaded fiber mat formulations have a shelf-life of at least 9 months when stored at -20 ¶øC and are stable when sterilized with ultraviolet light. The in vivo biocompatibility of these fibers was confirmed in a porcine excisional wound model by the (i) lack of inflammatory response to the terpolymers and their degradation products, and (ii) normal progression of healing evaluated for 28 days. Finally, a porcine excised hot comb burn model suitable for testing topical therapies was developed and used to evaluate the efficacy of P12-loaded fiber mats on the limitation of burn injury progression. The in vivo results suggest that P12-loaded ultrafast fiber mats may potentially limit burn injury progression. In conclusion, electrospun tyrosine-derived fiber mats offer the potential for topical clinical therapies that require ultrafast or fast delivery of the therapeutic agent.