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Integration And Remodeling Of Bioprinted Skin In Full-Thickness Wound Healing

生物打印皮肤在全层伤口愈合中的整合和重塑

基本信息

批准号：
10525225
负责人：
ADAM JORGENSEN
金额：
$ 5.43万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-11-18 至 2023-11-17
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10525225
关键词：
3-Dimensional Acceleration Achievement Address Adipocytes Anatomy Autologous Autologous Transplantation Automobile Driving Biocompatible Materials Biomedical Engineering Biomimetics Blood Vessels Blood capillaries Burn injury Cell Proliferation Cells Cicatrix Clinical Competence Complex Contracture Cosmetics Dermal Dermatology Dermis Endothelial Cells Endothelial Growth Factors Environment Epidermis Epithelium Extracellular Matrix Fellowship Fibroblasts Future Goals Hair Hair follicle structure Harvest Human Image In Vitro Infiltration Knowledge Life Measures Melanins Mentorship Military Personnel Morbidity - disease rate Mus Myofibroblast Natural regeneration PECAM1 gene Papillary Patients Phase Physicians Physiology Pigmentation physiologic function Pigments Population Procedures Production Quality of life Quantitative Reverse Transcriptase PCR Reconstructive Surgical Procedures Regenerative Medicine Research Personnel Research Training Science Scientist Sebaceous Glands Site Skin Skin Pigmentation Skin Substitutes Skin Tissue Skin graft Stains Structure Students Subcutaneous Tissue Sweat Glands Techniques Testing Thick Time Tissue Engineering Tissues Training Transforming Growth Factor beta Transplantation Treatment Cost United States Vascular Endothelial Cell Vascularization bioprinting burn wound career cell type clinical training cost estimate density digital doctoral student epithelial wound human tissue improved in vivo innovation insight keratinocyte meetings melanocyte meter migration mortality multidisciplinary neovascularization nerve supply novel strategies prototype regeneration potential restoration skin barrier standard of care student training third degree burn von Willebrand Factor wound wound bed wound closure wound healing

项目摘要

PROJECT SUMMARY This project will provide multidisciplinary training for a dual-degree MD/PhD student in skin tissue engineering and burn reconstructive surgery, addressing an unmet clinical need for a skin substitute with full-regeneration potential. Burn injuries are a major clinical burden in the United States, with nearly 500,000 patients treated annually, a mortality rate of 4.9%, and an estimated cost of $2 billion per year. The standard of care for burn injuries includes autologous skin grafting, but these procedures require sufficient harvest sites that are scarce in patients with severe wounds. Tissue-engineered skin substitutes offer a promising alternative to skin grafts. However, current prototypes contain only up to two cell types; lack sweat and sebaceous glands, hair follicles, and pigmentation; and may not stimulate revascularization and innervation. Since the ultimate goal of a skin graft is to regenerate authentic anatomy and physiology of native skin, there is an immense need to develop bioengineered skin with more cell types and full regeneration potential. To meet the need for bioengineered skin, bioprinting techniques have been developed to more accurately engineer tissue substitutes with appropriate 3D structural organization. This proposal will test the hypothesis that a 3D bioprinted skin graft will support regeneration of native-like skin in full-thickness wounds in vivo, similar to skin autografts. To test this hypothesis, the fellowship applicant has proposed three Specific Aims. Aim 1 will delineate how bioprinted skin accelerates epidermal barrier formation in vivo. This aim will provide the applicant with training in digital planimetry analysis to measure rates of wound closure, and NOVATM dermal phase meter analysis to measure the extent of re-epithelialization over time. Aim 2 will explore how neovascularization occurs in bioprinted skin in vivo and will require competence qrtPCR to measure endothelial growth factors compared with IHC stained capillaries per mm2. Aim 3 will investigate how melanocyte migration impacts bioprinted skin pigmentation. This will require immunohistochemical staining to determine mouse vs. human tissue formation, hair follicle formation, and melanin production. The applicant has assembled a multidisciplinary team of sponsors, co- sponsors, contributors, and consultants with expertise in regenerative medicine, ECM imaging, biomaterials science, wound healing, dermatology, and burn reconstructive surgery. They have established a training plan with (1) Mentorship Meetings, (2) Coursework, (3) Research Training, and (4) Clinical Training that will allow the student to develop both technically and conceptually towards becoming an independent skin tissue engineer. This novel approach to treatment of full-thickness wounds, conducted at a world-class institute, will serve as a basis for the student's training, and allow this promising applicant to develop as a physician- scientist poised to address future deficits in burn reconstructive surgery through skin tissue engineering.

项目总结