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

项目总结 该项目将为皮肤组织工程的双学位医学/博士研究生提供多学科培训 和烧伤重建手术，解决了临床上尚未满足的具有完全再生能力的皮肤替代品的需求 潜力。烧伤是美国的主要临床负担，有近50万名患者接受了治疗 每年的死亡率为4.9%，估计每年的成本为20亿美元。烧伤的护理标准 损伤包括自体皮肤移植，但这些程序需要足够的收获场地，而这些地方是稀缺的。 在有严重创伤的病人身上。组织工程皮肤替代品为皮肤移植提供了一种很有前途的替代方案。 然而，目前的原型只包含两种类型的细胞；缺乏汗腺和皮脂腺，毛囊， 和色素沉着；并且可能不会刺激血管重建和神经支配。因为皮肤的最终目标是 移植是为了再生原汁原味的天然皮肤解剖和生理，有极大的发展需求 拥有更多细胞类型和完全再生潜力的生物工程皮肤。以满足对生物工程的需求 皮肤，生物打印技术已经被开发出来，以更准确地设计组织替代品 适当的三维结构组织。这项提议将检验3D生物打印皮肤移植将 支持体内全层创面中天然类皮肤的再生，类似于自体皮肤移植。为了测试这一点 假设，奖学金申请者提出了三个具体目标。目标1将描绘生物打印的皮肤如何 在体内加速表皮屏障的形成。这一目标将为申请者提供数字培训 平面测量法测量伤口闭合率，NOVATM真皮相位仪分析测量 随时间推移重新上皮化的程度。目标2将探索生物打印皮肤中新生血管是如何发生的 在活体内，将需要能力qrt聚合酶链式反应来检测内皮生长因子与免疫组化染色的比较 每平方毫米的毛细血管数。目标3将调查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来确定小鼠和人类组织的形成，毛囊 形成和产生黑色素。申请人已经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、ECM成像、生物材料专业知识的顾问 科学、伤口治疗、皮肤科和烧伤重建外科。他们已经制定了一个训练计划 通过(1)导师会议，(2)课程作业，(3)研究培训，和(4)临床培训，将允许 学生在技术和概念上都要发展成为独立的皮肤组织 工程师。这种在世界级研究所进行的治疗全层伤口的新方法将 作为学生培训的基础，并允许这位有前途的申请者发展成为一名医生- 科学家准备通过皮肤组织工程解决烧伤重建手术中未来的缺陷。

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.