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：
10063419
负责人：
ADAM JORGENSEN
金额：
$ 5.1万
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/10063419
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 Epithelial Extracellular Matrix Fellowship Fibroblasts Future Goals Hair Hair follicle structure Harvest Human Image In Vitro Infiltration Institutes Knowledge Life Measures Melanins Mentorship Military Personnel Morbidity - disease rate Mus Myofibroblast Natural regeneration Organ Transplantation 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 Vascularization bioprinting burn wound career cell regeneration cell type 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 organizational structure prototype regeneration potential restoration skin barrier standard of care student training third degree burn three dimensional structure 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.

项目概要该项目将为皮肤组织工程双学位医学博士/博士生提供多学科培训和烧伤重建手术，解决了对完全再生皮肤替代品的未满足的临床需求潜在的。烧伤是美国的主要临床负担，有近 50 万名患者接受治疗每年，死亡率为 4.9%，估计每年花费 20 亿美元。烧伤护理标准损伤包括自体皮肤移植，但这些手术需要足够的采集部位，而这些部位是稀缺的对于有严重伤口的患者。组织工程皮肤替代品为皮肤移植提供了一种有前景的替代方案。然而，当前的原型仅包含最多两种细胞类型；缺乏汗液和皮脂腺、毛囊，和色素沉着；并且可能不会刺激血运重建和神经支配。既然皮肤的最终目标移植是为了再生原生皮肤的真实解剖学和生理学，因此非常需要开发生物工程皮肤具有更多细胞类型和充分的再生潜力。为了满足生物工程的需要皮肤生物打印技术的发展可以更准确地设计组织替代品适当的 3D 结构组织。该提案将检验 3D 生物打印皮肤移植物将支持体内全层伤口中类天然皮肤的再生，类似于自体移植皮肤。为了测试这个假设，奖学金申请人提出了三个具体目标。目标 1 将描述如何生物打印皮肤加速体内表皮屏障的形成。这一目标将为申请人提供数字化培训面积测量分析用于测量伤口闭合率，NOVATM 真皮相位计分析用于测量随着时间的推移，再上皮化的程度。目标 2 将探索生物打印皮肤中新血管形成的发生方式体内，与 IHC 染色相比，需要有能力 qrtPCR 来测量内皮生长因子每平方毫米的毛细管数。目标 3 将研究黑素细胞迁移如何影响生物打印的皮肤色素沉着。这需要免疫组织化学染色来确定小鼠与人体组织形成、毛囊的形成和黑色素的产生。申请人组建了一个由赞助商、合作伙伴组成的多学科团队具有再生医学、ECM 成像、生物材料专业知识的赞助商、贡献者和顾问科学、伤口愈合、皮肤病学和烧伤重建手术。他们制定了培训计划包括 (1) 导师会议、(2) 课程作业、(3) 研究培训和 (4) 临床培训学生在技术和概念上发展成为独立的皮肤组织工程师。这种在世界一流的研究所进行的治疗全层伤口的新颖方法将作为学生培训的基础，并让这位有前途的申请人发展成为一名医生- 科学家准备通过皮肤组织工程解决烧伤重建手术的未来缺陷。