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.

项目摘要该项目将为皮肤组织工程中的双度MD/PHD学生提供多学科培训并燃烧重建手术，以满足的临床需求未满足，以全新的临床替代品潜在的。烧伤受伤是美国的主要临床负担，接受了近500,000名患者每年，死亡率为4.9％，估计每年成本20亿美元。烧伤的护理标准伤害包括自体皮肤移植，但是这些过程需要足够的收获地点在严重伤口的患者中。组织工程的皮肤替代品为皮肤移植物提供了有希望的替代品。但是，当前的原型仅包含多达两种细胞类型。缺乏汗水和皮脂腺，毛囊，和色素沉着；并且可能不会刺激血运重建和神经。由于皮肤的最终目标移植物是为了再生原生皮的真实解剖学和生理学，巨大的需要发展具有更多细胞类型和充分再生潜力的生物工程皮肤。满足生物工程的需求皮肤，生物打印技术已经开发出来更准确地与组织替代品设计适当的3D结构组织。该提案将检验以下假设：3D生物打印的皮肤移植在体内的全厚性伤口中支持本地皮肤样皮肤的再生，类似于皮肤自体移植。测试这个假设，奖学金申请人提出了三个具体目标。 AIM 1将描绘出生物打印的皮肤在体内加速表皮屏障形成。这个目标将为申请人提供数字培训计划分析以测量伤口闭合率和Novatm真皮相表分析以测量随着时间的流逝，重新上皮化的程度。 AIM 2将探索生物打印的皮肤中新生血管化是如何发生的体内，将需要QRTPCR能力来测量内皮生长因子与IHC染色相比毛细血管 / mm2。 AIM 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。这将需要免疫组织化学染色，以确定小鼠与人体组织形成，毛囊形成和黑色素产生。申请人组建了一个由赞助商组成的多学科团队，共同赞助商，贡献者和具有再生医学专业知识，ECM成像，生物材料专业知识的顾问科学，伤口愈合，皮肤病学和烧伤重建手术。他们已经建立了培训计划（1）指导会议，（2）课程工作，（3）研究培训和（4）临床培训将允许学生在技术上和概念上发展成为独立的皮肤组织工程师。在世界一流学院进行的这种全厚性伤口治疗的新型方法将作为学生培训的基础，允许该有前途的申请人成长为医师 - 科学家准备通过皮肤组织工程来解决燃烧重建手术的未来缺陷。