In Situ Skin Regeneration and Angiogenesis for Full-Thickness Burns

及时封闭创面是预防大面积烧伤患者感染和脓毒症的关键 受伤。与治疗这些患者相关的最常见的挑战是缺乏可用的供体皮肤。 尽管治疗深度烧伤的新技术不断涌现，但目前只有一种可用于商业用途。 用于治疗全层烧伤(培养的自体上皮移植，CEAS)。CEAS是一种挽救生命的治疗方法 然而，它们非常易碎，容易损坏，需要3周的时间才能制造出来。最早 伤口闭合可降低感染、液体流失、死亡率和疤痕形成的风险，快速和 需要永久闭合全层伤口，以提高存活率和改善预后。海流 使用细胞喷雾快速原位再生全层创面的障碍包括缺乏可存活的真皮， 低植入效率和多变的喷雾细胞存活率。我们的团队最近开发出了同种异体 具有激光消融真皮乳头的真皮替代物可显著促进角质形成细胞的增殖。这 再生平台，由新鲜分离的自体细胞喷雾和现成的同种异体真皮组成 具有激光微图案化真皮乳头和生长因子负载快速释放纳米粒的模板，是 建议通过增强喷雾皮肤细胞的粘附性和存活率来促进伤口的快速永久愈合 和快速的血管生成。在目标1中，喷雾皮肤细胞植入和存活率将作为一项功能进行检查。 激光微纹真皮乳头的形式(宽度、长度、角度)。目标2寻求进一步增强 通过增强血管生成促进皮肤细胞存活和表皮再生。血管的作用 释放血管内皮细胞生长因子/血小板衍生生长因子，高表面积体积比 聚多巴胺(PDA)纳米粒对血管生成速度和程度及下游表皮的影响 再生将在小鼠模型中进行评估，然后是高度平移的猪模型。在《目标3》中， 将制作梯度胶原-丝质支架，以减少伤口的收缩，同时提供物理 以及促进表皮再生的化学环境。最后，对完全优化后的激光器的效率进行了测试 微图案化真皮模板(真皮乳头形式、血管内皮生长因子/PDGF-PDA载量和浓度以及 支架力学)将在猪烧伤模型中与标准的自体移植和喷雾进行比较 只有皮肤细胞。拟议的研究利用了再生医学、血管形成和大血管移植方面的专业知识 动物模型开发一种新的、即用即用的技术，可以显著改变治疗方法 患者遭受大面积烧伤，并改善预后和生活质量。

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.