Multicomponent hydrogels activating wound-induced hair neogenesis for scarless wound healing.

Proposal Summary/Abstract Candidate: Dr. Leo Wang holds a BA, MS, MD, and PhD from the University of Pennsylvania, where he completed dermatology residency and currently is a Clinical Instructor and postdoctoral fellow working with Dr. George Cotsarelis in the Department of Dermatology. In 2025, Dr. Wang will be appointed as Assistant Professor in the tenure track and provided a generous startup and laboratory space as an independent researcher. Support from the DP5 award will enable the pursuit of the proposed research in Dr. Wang’s future laboratory. Environment: The proposed research will be conducted in the Department of Dermatology at the University of Pennsylvania, which is committed to Dr. Wang’s career development and mentorship. The Department of Dermatology is consistently top ranked in NIH funding with the support of a NIH P30 Skin Biology and Disease Resource-based Center, which enhances research and collaboration across the University. The School of Engineering and Applied Sciences is a block away from the School of Medicine, allowing Dr. Wang to maintain multidisciplinary collaborations. Research: Human skin wounds typically heal with fibrotic scars, leading to impaired form and function, characterized by the loss of appendages like hair follicles. Scarless wound healing requires hair follicles, which are rich in stem cells and factors that can prevent and treat scars. While humans do not regenerate hair follicles, mice do so in large full-thickness wounds through wound-induced hair neogenesis (WIHN), involving sequential upregulation of Wnt and Sonic hedgehog (Shh) signaling. This proposal aims to spatiotemporally activate Wnt and Shh signaling using a two-component hydrogel that releases CHIR99021, a Wnt agonist, and HhAg1.5, a Shh agonist, to promote hair follicle neogenesis and treat scars. Hydrogels will be engineered with microcapsules for tunable release of CHIR and HhAg, tested to induce WIHN and prevent scarring, and fabricated into microneedle patches to simultaneously wound and induce hair neogenesis, and treat fibrotic, mature human scars. This research will demonstrate that biomaterials can control exogenous signals to prevent and treat scars through hair follicle neogenesis, advancing the understanding of WIHN and expanding approaches to controlled delivery. Most importantly, this will lead to a therapeutic that can be injected into skin after surgery or trauma to prevent scars, or applied as patches to treat mature scars, which could transform clinical care.