In Situ Skin Regeneration and Angiogenesis for Full-Thickness Burns

全层烧伤的原位皮肤再生和血管生成

• 批准号: 10587297
• 负责人: Mahmood Khan
• 金额: $ 65.8万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10587297
• 关键词: Adhesions; Allogenic; Animal Model; Area; Autologous; Autologous Transplantation; Biopolymers; Burn injury; Cell Adhesion; Cell Survival; Cells; Chemicals; Cicatrix; Collagen; Collagen Type I; Data; Dermal; Dermis; Development; Emerging Technologies; Engineered skin; Engraftment; Environment; Epidermal Ridges; Epidermis; Epithelium; Family suidae; Goals; Growth Factor; In Situ; Infection prevention; Lasers; Length; Length of Stay; Life; Liquid substance; Mechanics; Modeling; Myofibroblast; Natural regeneration; Nutrient; Oxygen; PDGFA gene; Patients; Pattern; Perfusion; Platelet-Derived Growth Factor; Predisposition; Procedures; Proliferating; Publications; Quality of life; Regenerative Medicine; Risk Reduction; Role; Sepsis; Silk; Skin; Skin graft; Speed; Surface; Technology; Testing; Thick; Tissue Donors; VEGFA gene; Vascular Endothelial Growth Factors; Vascularization; Width; angiogenesis; burn model; burn wound; design; functional improvement; improved; improved outcome; in vivo; infection risk; keratinocyte; manufacture; mortality; mouse model; nanoparticle; new technology; novel; paracrine; platelet-derived growth factor BB; porcine model; regenerative; release factor; scaffold; second degree burn; skin regeneration; stemness; survival outcome; third degree burn; tongue papilla; wound; wound closure; wound healing

Prompt closure of wounds is critical to prevention of infection and sepsis in patients suffering massive burn injuries. The most common challenge associated with treating these patients is the lack of available donor skin. Although new technologies are emerging to treat deep partial thickness burns, only one is commercially available for the treatment of full-thickness burns (cultured epithelial autografts, CEAs). CEAs are a life-saving treatment option; however, they are extremely fragile, prone to damage and require > 3 weeks to manufacture. As early wound closure reduces the risk of infection, fluid loss, mortality and scarring, strategies to quickly and permanently close full-thickness wounds are needed to increase survival and improve outcomes. The current obstacles to rapid in situ regeneration of full-thickness wounds using cell sprays include the lack of viable dermis, low engraftment efficiency and variable survivability of spray-on cells. Our team recently developed allogeneic dermal substitutes with laser ablative dermal papillae that significantly enhanced keratinocyte proliferation. This regenerative platform, consisting of freshly isolated autologous cell sprays and an off-the-shelf, allogeneic dermal template with laser micropatterned dermal papillae and growth factor loaded rapid release nanoparticles, is proposed to facilitate rapid, permanent wound closure via enhanced adhesion and survival of spray-on skin cells and rapid angiogenesis. In Aim 1, spray-on skin cell engraftment and survivability will be examined as a function of the form of the laser micropatterned dermal papillae (width, length, angle). Aim 2 seeks to further enhance spray-on skin cell survivability and epidermal regeneration via enhanced angiogenesis. The role of vascular endothelial growth factor (VEGF)/ platelet-derived growth factor (PDGF)-releasing, high surface area to volume polydopamine (PDA) nanoparticles on the rate and extent of angiogenesis and downstream epidermal regeneration will be assessed in a mouse model followed by a highly translational porcine model. In Aim 3, gradient collagen-silk scaffolds will be fabricated to reduce contraction of the wounds while providing a physical and chemical environment that promotes epidermal regeneration. Finally, the efficacy of the fully optimized laser micropatterned dermal template (dermal papillae form, VEGF/PDGF-PDA loading and concentration and scaffold mechanics) will be examined in a porcine burn model compared to standard autografting and spray-on skin cells alone. The proposed studies leverage the expertise in regenerative medicine, vascularization and large animal models to develop a novel, immediate use technology that can dramatically transform treatment for patients suffering from massive burn injuries and improve outcomes and quality of life.

迅速关闭伤口对于预防大量烧伤的患者的感染和败血症至关重要 受伤。与治疗这些患者有关的最常见挑战是缺乏可用的供体皮肤。 尽管新技术正在出现以治疗深度厚度燃烧，但只有一种可商购 为了治疗全厚度燃烧（培养的上皮自体移植，CEAS）。 CEAS是一种挽救生命的待遇 选项;但是，它们非常脆弱，容易损坏，需要> 3周才能制造。尽早 伤口闭合会降低感染，流体丧失，死亡率和疤痕，策略的风险，快速和 需要永久闭合全厚性伤口来增加生存并改善预后。电流 使用细胞喷雾剂的全厚性伤口快速原位再生的障碍包括缺乏可行的真皮， 喷雾细胞的低植入效率和可变生存能力。我们的团队最近开发了同种异体 用激光烧蚀皮肤乳头乳头替代品，可显着增强角质形成细胞增殖。这 再生平台，由新鲜孤立的自体细胞喷雾剂和现成的同种异体真皮组成 带有激光微图案皮肤乳头和生长因子的模板加载快速释放纳米颗粒，为 提议通过增强的喷涂皮肤细胞的粘附和存活来促进快速，永久性的伤口闭合 和快速的血管生成。在AIM 1中，将检查喷雾细胞植入和生存能力作为功能 激光微图案皮肤乳头（宽度，长度，角度）的形式。 AIM 2试图进一步增强 通过增强的血管生成，喷涂皮肤细胞的生存能力和表皮再生。血管的作用 内皮生长因子（VEGF）/血小板衍生的生长因子（PDGF） - 释放，高表面积至体积 关于血管生成的速率和程度和下游表皮的聚多巴胺（PDA）纳米颗粒 再生将在小鼠模型中评估，然后是高度转化的猪模型。在AIM 3中， 梯度胶原蛋白 - silk脚手架将被制造以减少伤口的收缩，同时提供物理 和促进表皮再生的化学环境。最后，完全优化激光的功效 微图案真皮模板（皮肤乳头状形式，VEGF/PDGF-PDA加载和浓度以及 与标准的自动化和喷涂相比，将在猪燃烧模型中检查脚手架力学） 单独使用皮肤细胞。拟议的研究利用了再生医学，血管和大型研究的专业知识 动物模型开发一种新颖的，即时使用技术，可以极大地改变治疗 遭受严重烧伤的患者，改善结果和生活质量。