A recombinant elastin skin substitute for the treatment of burns

用于治疗烧伤的重组弹性蛋白皮肤替代品

• 批准号: 10601801
• 负责人: Stefan Roberts
• 金额: $ 28.24万
• 依托单位: INSOMA BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10601801
• 关键词: Address; Adult; Animals; Autologous Transplantation; Biocompatible Materials; Biomechanics; Biopsy; Blood Vessels; Board Certification; Burn injury; Cells; Cellular Infiltration; Cicatrix; Collagen; Collagen Fiber; Cytoskeleton; Data; Debridement; Deposition; Dermal; Dermis; Development; Elasticity; Elastin; Evaluation; Excision; Failure; Family suidae; Fermentation; Fibrosis; Formulation; Generations; Goals; Growth; Harvest; Histology; Human; In Vitro; Infection; Infiltration; Inflammatory Response; Injury; Marketing; Methods; Modeling; Modification; Modulus; Molds; Mus; Natural regeneration; Operative Surgical Procedures; Outcome; Pathologist; Patient-Focused Outcomes; Patients; Phase; Phase Transition; Physiology; Pliability; Polymers; Porosity; Positioning Attribute; Preparation; Procedures; Process; Production; Property; Proteins; Protocols documentation; Recombinant Proteins; Recombinants; Rod; Safety; Second Look Surgery; Site; Skin; Skin Substitutes; Skin Tissue; Skin graft; Skin repair; Smooth Muscle; Stretching; Structure; Supervision; Surgical sutures; Temperature; Testing; Thick; Time; Tissues; Vascularization; acute wound; angiogenesis; biomaterial compatibility; brass; burn model; burn therapy; burn wound; chronic wound; cost; cost effective; crosslink; density; design; flexibility; healing; improved; in vivo; in vivo evaluation; keratinocyte; manufacturing process; manufacturing scale-up; mechanical properties; mimetics; mouse model; porcine model; preclinical toxicity; programs; protein purification; repaired; resilience; severe burns; skin regeneration; standard of care; subcutaneous; success; virtual; wound; wound healing; wound treatment; wound vascularization

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.

项目摘要 本项目的目标是优化和评估inSoma Bio的专有重组弹性蛋白为基础的 生物材料Fractomer®作为一种有效、低成本的皮肤移植支持基质，用于治疗严重烧伤 伤口烧伤最成功的治疗方法是手术切除，然后植皮;然而， 严重损伤的患者没有足够的健康皮肤来支持自体移植手术。为了解决这个 根据需要，已经开发了生物材料基质，例如Integra Wound Matrix®，其减少感染， 当应用于烧伤伤口时，促进血管形成并支持真皮组织的再生。当前 真皮替代品市场价值超过70亿美元，主要由动物源性胶原蛋白主导， 从组织中分离胶原蛋白的既定工艺和安全性的历史先例。但由于 从动物身上收获的成本，他们是出了名的昂贵，与一个单一的40平方厘米的Integra成本 患者~ 1万美元。此外，胶原蛋白不能复制天然皮肤的弹性，用弹性蛋白，而不是胶原蛋白， 使皮肤具有弹性和柔韧性。由于弹性蛋白的产生在成年期几乎停止， 由于缺乏弹性蛋白，导致新发育的皮肤出现疤痕。因此，至少三分之一的烧伤治疗 使用这些材料需要手术修复。inSoma的Fractomer®生物材料由重组 弹性蛋白模拟蛋白，并且代表了用于生产新的皮肤移植基质的理想基质， 更好地复制皮肤的独特生物力学特性。该材料已被证明支持在体内 在体内试验过程中， 鼠和猪模型，并且由于其温度敏感的相变性质，可以容易地 模制成几乎任何形式，包括皮肤状片。在这里提出的第一阶段计划中，该公司 将继续优化Fractomer板材结构和成型方法，以生产一种支持 通过血管化、细胞浸润和有组织的胶原蛋白沉积进行真皮再生。猪 烧伤模型将用于比较Fractomer与Integra Wound Matrix®（当前的金标准） 皮肤移植支持基质中。移植物结局的预期改善（例如，收缩更少， 直接拒绝）代表了一种高度破坏性的 目前的皮肤修复基质市场。