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Synthetic Developmental Tissue Engineering of Human Hair Follicles

人类毛囊的合成发育组织工程

基本信息

批准号：
10609188
负责人：
Hasan Erbil Abaci
金额：
$ 5.78万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-12 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10609188
关键词：
3-Dimensional 3D Print Address Afferent Neurons Alopecia Biological Assay Biomedical Engineering Blood Vessels Burn injury Cells Chronic Cicatrix Coculture Techniques Collaborations Complex Cues Data Dermal Detection Development Dissection Engineered skin Engineering Engraftment Ensure Epidermolysis Bullosa Extracellular Matrix Fibroblasts Gene Expression Profile Generations Genes Genetic Genetic Skin Diseases Genetic Transcription Goals Hair Hair Cells Hair Diseases Hair follicle structure Hepatocyte Human Human Engineering Immune In Vitro Infection Manuals Medical Mentorship Mesenchymal Methods Microfabrication Monitor Morphogenesis Mus Natural regeneration Neurons Organ Pathway Analysis Patients Physiological Regenerative Medicine Regulator Genes Replacement Therapy Research Reverse engineering Skin Skin Substitutes Skin Tissue Skin graft Skin injury Somatic Cell Systems Biology Techniques Technology Therapeutic Tissue Engineering Ulcer Vascularization Work appendage base bioprinting cell type chronic wound decubitus ulcer density design diabetic ulcer differential expression effective therapy gene induction gene network genetic approach genetic signature heat injury improved improved outcome in vivo interest novel overexpression restoration skin disorder success tongue papilla transcription factor wound healing

项目摘要

Project Summary Human skin equivalents (HSEs) have provided an effective therapy for patients with significant skin loss due to burns, ulcers and genetic skin diseases; however they still have various limitations including poor viability and lack of appendages or mismatch in hair density. We have recently improved the viability of skin grafts by establishing a method to micropattern vasculature in HSEs. On the other hand, it still remains a prevailing challenge to engineer functional skin grafts with hair follicles since long-term cultured human dermal papilla cells (DPCs) in vitro lose their hair-inducing capacity. The overall goal of this project is to engineer viable and functional skin equivalents with appendages using cultured human cells. We will employ bioengineering, genetics and systems biology approaches to reprogram cultured DPCs and dermal fibroblasts into hair inductive cells. These cells will then be used to generate hair-bearing 3D skin equivalents, enabling the development of truly functional skin substitutes for patients with significant skin/hair loss. In particular, we will use i) microfabrication techniques to recapitulate 3D hair follicle microenvironment (microenvironmental approach) and ii) reverse engineering gene network analysis to reprogram hair inductive gene signatures of cultured DPCs and fibroblasts (genetic approach). Finally, taking advantage of our recently established technique for vascularization, we will develop viable HSEs that, after engraftment, can controllably regenerate hair and remain fully integrated due to enhanced revascularization. The ability to regenerate an entire hair follicle from cultured human cells will have an overwhelming positive impact on the medical management of different types of alopecia, epidermolysis bullosa as well as chronic wounds, severe infections, and burns, all of which represent major unmet medical needs. The ability to generate a hair-bearing skin is a crucial step towards making a truly functional human skin and would mark a dramatic conceptual advance in regenerative medicine approaches to disorders of the skin and hair follicle, such as hair loss, as well as improve the outcome of severe skin injuries leading to disfiguring scars.

项目总结