(123g) Bioactive Materials for Tissue Repair

Complications associated with ineffective tissue repair including in slow or non-healing wounds, cost the US healthcare system ~$20 billion / year and amount to ~5% of the total cost of Medicare and Medicaid. In cases of surgical closure, lack of immediate tissue approximation, high potential for scarring, including in visible areas of the body, susceptibility to infection, and long procedure times necessitate new approaches for tissue repair especially for unmet needs where current approaches are suboptimal in performance. Light-activated tissue sealing is an emerging strategy that facilitates rapid, liquid-tight approximation of ruptured tissues, but the lack of effective biomaterials compromises efficacy of tissue repair. I will discuss our advances in the generation, characterization, evaluation, and of laser-activated sealant (LASE) biomaterials for the rapid sealing and repair of incisional wounds. Use of bioactive therapeutics that facilitate early tissue repair or combat infection further enhanced the efficacy of this approach. In addition to acute trauma, slow-healing and chronic wounds, including in diabetic and obese patients, are a significant cause for morbidity. Advanced biologics have shown some promise but have largely not succeeded in cases of intractable wound pathologies, and the last biologic approved for diabetic wounds was over 25 years ago. I will describe our new findings on the delivery of immunomodulating bioactive molecules e.g., histamine receptor agonists and silk-nanomaterials for kickstarting early stages of tissue repair, which are largely dysfunctional in diabetic wounds. I will also discuss new findings on the effect of polypeptide structure-immunomodulation activity and transcriptional responses to silk nanomaterials in wounds. An approach to temporal delivery in which, timing the delivery of bioactives to modulate individual stages of tissue repair leads to early wound closure in healthy and diabetic obese mice will also be discussed. Novel biomacromolecules designed to stimulate histamine pathways for effective tissue repair will also be discussed. Our approach on biomaterials innovation, light-activated sealing, histamine receptor agonism, and temporal bioactive delivery will lead to new therapeutic interventions for tissue repair and regeneration.