Engineering Hair Follicles in Vascularized D Skin Models

ABSTRACT Each year more than one million patients are hospitalized in the U S for significant skin loss due to thermal and pressure injuries chronic diabetic ulcers or genetic skin diseases The ability to generate engineered human skin equivalents HSEs has provided a promising and effective therapy for these patients However currently available HSEs still have various limitations including poor viability and lack of appendages or mismatch in hair density Skin is a complex organ which contains more than different cell types and various components such as vasculature hair follicles sensory neurons and immune cells The field of skin tissue engineering and regenerative medicine is currently limited by the lack of skin models that recapitulate the anatomy and physiology of human skin This research will advance the generation of high fidelity engineered skin grafts with functional appendages to be used in skin replacement therapy as well as modeling skin disorders in D Our recent work has improved the viability of skin grafts by establishing a method to micropattern vasculature in HSEs however it still remains a prevailing challenge to incorporate hair follicles into engineered skin grafts in order to improve wound healing and skin function The goal of this project is to engineer viable and functional skin equivalents with hair follicles and vasculature using exclusively cultured human cells for future use in drug screening and clinical applications These studies will address several prevailing challenges in the field of skin hair tissue engineering by achieving i efficient hair induction using cultured human DPC ii initiation of hair morphogenesis in D human skin equivalents in vitro iii control over region specific hair density iv viable skin grafts through promoting adequate vascularization and v combination of a vasculature network with hair follicles to build increase the complexity of existing D skin models This project is highly responsive to several of the areas of interest in this RFA AR including Sophisticated skin models that incorporate multiple skin components such as hair follicles vasculature nerves sweat glands immune cells and fat Add complexity to existing model systems and Engineering functional stem cell niches in D musculoskeletal and skin models We will employ bioengineering genetics pharmacological and systems biology approaches to address this hypothesis allowing for the development of truly functional and viable skin substitutes for patients with significant skin hair loss and providing D in vitro screening models of skin and hair follicles for pharmaceutical development applications NARRATIVE The field of skin tissue engineering and regenerative medicine is currently limited by the lack of skin models that recapitulate the anatomy and physiology of human skin The goal of this project is to engineer viable and functional skin equivalents with hair follicles and vasculature using exclusively cultured human cells for future use in drug screening and clinical applications We will employ bioengineering genetics pharmacological and systems biology approaches to address this hypothesis allowing for the development of truly functional and viable skin substitutes for patients with significant skin hair loss and providing D in vitro screening models of skin and hair follicles for pharmaceutical development applications