Multifunctional Intelligent Hierarchical Fibrous Biomaterials Integrated with Multimodal Biosensing and Feedback-Based Interventions for Healing Infected Chronic Wounds

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Project Summary Chronic wounds arise as a consequence of diabetes, venous dysfunction, aging, surgeries or others and pose a major healthcare challenge in the United States. For example, 20-25% of diabetic patients develop foot ulcers (a type of chronic wounds) and about 63.4% of them develop infections. Failure to prevent or manage infections results in high healthcare cost, amputations, and an increased mortality. Despite recent progress in wound care, the effective treatment of infected chronic wounds remains challenging. One problem is the lack of biomaterial scaffolds that can simultaneously combat wound infection and promote wound tissue regeneration. The other problem is the inability to monitor the wound in real time and offer feedback-based, pharmacological interventions. Also, frequent hospital visits associated with existing methods increase the patient's exposure risk to contagious diseases (e.g., COVID-19). Thus, there is an urgent need to develop new telemedicine therapies for home-based, effective treatment of infected chronic wounds. The objective of this project is to develop intelligent hierarchical fibrous biomaterials, consisting of vertically aligned microfibers on the bottom (promoting granulation tissue for- mation), radially aligned nanofibers on the top (accelerating re-epithelialization), and multimodal bioelectronics integrated on nanofibers (monitoring the wound status and providing iontophoresis-controlled multiple drug de- livery), to treat infected chronic wounds. The central hypothesis is judiciously designed hierarchical fibrous bio- materials, together with on-demand multistage pharmacological interventions guided by real-time wound moni- toring, can effectively combat infections/biofilms and promote wound healing. Two specific aims include (1) fab- ricating and characterizing intelligent biomaterials and (2) evaluating efficacy of intelligent biomaterials in moni- toring wound status, combating infections and promoting wound healing using diabetic mice wounds and ex vivo human skin wounds. The proposed intelligent biomaterial is innovative as compared to existing smart dressings in light of its biodegradable hierarchical fibrous biomaterial that can promote wound tissue regeneration, its inte- grated multimodal bioelectronics capable of providing comprehensive information of wound status and offering feedback-based, multistage delivery of antibiotics and growth factors, and in vivo and ex vivo evaluations using both diabetic mice wounds and human skin explants to identify existing issues and accordingly improve designs and fabrications. Also, the correlations of the wound status/healing, sensor readouts and delivered drug amounts will be established in this research, which are still lacking. The research team's complementary expertise, past collaboration experiences and collaboratively generated preliminary results form the basis for the success of this project. Results from this project will contribute to development of translational telemedicine products that can improve the efficacy of chronic wound care, decrease healthcare costs, and most importantly reduce the rates of amputation and modality and improve quality of life of patients, which can also lay foundations for development of other closed-loop biomedical systems for treating heart diseases and promoting bone and neural regeneration.