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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要该项目的目标是优化和评估 inSoma Bio 专有的基于重组弹性蛋白的生物材料 Fractomer® 作为一种有效、低成本的植皮支持基质，用于治疗严重烧伤烧伤最成功的治疗方法是手术切除，然后进行植皮；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。根据需要，已经开发了生物材料基质，例如 Integra Wound Matrix®，可以减少感染，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。价值超过 70 亿美元的真皮替代品市场以动物源性胶原蛋白为主，因为其良好的性能然而，由于安全性的原因，已经建立了从组织中分离胶原蛋白的工艺和历史先例。从动物身上获取的成本非常昂贵，单张 40 平方厘米的 Integra 片材成本为病人〜10k美元此外，胶原蛋白不能复制天然皮肤的弹性，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，因为弹性蛋白的产生在成年后几乎停止，收缩。由于缺乏弹性蛋白会导致新发育的皮肤出现疤痕，因此至少有三分之一的烧伤治疗。使用这些材料需要进行手术修复。inSoma 的 Fractomer® 生物材料由重组制成。弹性蛋白模拟蛋白，是生产新皮肤移植基质的理想基质该材料已被证明可以更好地复制皮肤的独特生物力学特性。体内测试期间的细胞浸润、有组织的胶原蛋白沉积、血管化和生物相容性小鼠和猪模型，由于其温度敏感的相变特性，可以很容易地在此处提出的第一阶段计划中，该公司将其模制成几乎任何形式，包括类皮肤片材。将继续优化 Fractomer 片材结构和形成方法，以生产支撑的材料通过血管化、细胞浸润和有组织的胶原蛋白沉积实现真皮再生。烧伤伤口模型将用于将 Fractomer 与当前的黄金标准 Integra Wound Matrix® 进行比较移植结果的预期改善（例如，更少的收缩并且没有）采用基于弹性蛋白的 Fractomer 移植材料代表了一种高度破坏性的技术产品进入当前的真皮修复基质市场。