A recombinant elastin skin substitute for the treatment of burns

项目摘要 该项目的目标是优化和评估in Soma Bio的专利重组弹性蛋白 生物材料Fractomer®作为治疗严重烧伤的有效、低成本植皮支持基质 伤口。烧伤的治疗最成功的方法是手术切除，然后植皮； 严重受损的患者没有足够的健康皮肤来支持自体移植手术。要解决这个问题 根据需要，已经开发了减少感染的生物材料基质，例如Integra Wound Matrix®， 适用于烧伤创面，促进血管生成，支持真皮组织再生。海流 价值超过70亿美元的真皮替换市场由动物来源的胶原蛋白主导，因为 已建立的从组织中分离胶原蛋白的工艺和安全的历史先例。然而，由于 从动物收获的成本，他们是出了名的昂贵，一张40 cm2的Integra纸需要花费 病人~10000美元。此外，胶原蛋白不能复制天然皮肤的弹性，只有弹性蛋白，而不是胶原蛋白， 为皮肤提供弹性和柔韧的特性。随着弹性蛋白的产生在成年期几乎停止，收缩 由于缺乏弹性蛋白会导致新生皮肤的惊吓。因此，至少三分之一的烧伤治疗 使用这些材料需要手术修改。InSoma的Fractomer®生物材料由重组 弹性蛋白模拟蛋白，是生产新的皮肤移植基质的理想基质， 更好地复制皮肤独特的生物力学特性。这种材料已经被证明在体内支持 体内试验期间的细胞渗透、有组织的胶原沉积、血管形成和生物相容性 小鼠和猪的模型，由于其温度敏感的相变特性，可以很容易地 几乎可以模制成任何形式，包括像皮肤一样的床单。在这里提出的第一阶段计划期间，该公司 将继续优化Fractomer薄板结构和成型方法，以生产支持 真皮再生通过血管化、细胞渗透和有组织的胶原沉积来实现。一头猪 烧伤创面模型将被用来比较Fractomer和目前的黄金标准Integra Wound Matrix® 在皮肤移植支持基质中。移植结果的预期改善(例如，较少的宫缩和无 完全排斥)通过使用基于弹性蛋白的Fractomer移植材料代表了一种高度破坏性的 产品推向目前真皮修复基质市场。

Project Summary The goal of this project is to optimize and evaluate inSoma Bio’s proprietary recombinant elastin-based biomaterial, Fractomer®, as an effective, low-cost skin grafting support matrix for the treatment of severe burn wounds. Burns are most successfully treated by surgical excision followed by skin grafting; however many patients with severe damage do not have sufficient healthy skin to support autograft procedures. To address this need, biomaterial matrices, such as Integra Wound Matrix®, have been developed which reduce infection, facilitate vascularization, and support regeneration of dermis tissue when applied to burn wounds. The current market for dermal replacement, valued at over $7 billion, is dominated by animal-derived collagen due to well established processes for isolating collagen from tissue and historical precedent for safety. However, due to the cost of harvest from animals, they are notoriously expensive, with a single 40 cm2 sheet of Integra costing the patient ~$10k. In addition, collagen cannot replicate the elasticity of natural skin, with elastin, not collagen, providing skin with its resilient and pliable properties. As elastin production all but halts in adulthood, contraction due to lack of elastin leads to scaring in newly developed skin. As a result, at least one third of burn treatments using these materials require surgical revision. inSoma’s Fractomer® biomaterial is made from recombinant elastin-mimetic proteins and represents an ideal substrate for the production of new skin grafting matrices which better replicate the unique biomechanical properties of skin. The material has been shown to support in vivo cellular infiltration, organized collagen deposition, vascularization, and biocompatibility during in vivo testing in both murine and porcine models and, due to its temperature-sensitive phase transition properties, can be readily molded into virtually any form including skin-like sheets. During the Phase I program proposed here, the company will continue optimizing Fractomer sheet structure and formation methods to produce a material which supports dermal regeneration through vascularization, cellular infiltration, and organized collagen deposition. A porcine model of burn wounds will be used to compare Fractomer to Integra Wound Matrix®, the current gold standard in skin grafting support matrices. The expected improvement in graft outcomes (e.g., fewer contractions and no outright rejections) by employing the elastin-based Fractomer graft material represents a highly disruptive product to the current dermal repair matrix market.