Novel peptide-impregnated hydrogel as a wound healing device

新型肽浸渍水凝胶作为伤口愈合装置

• 批准号: 10474270
• 负责人: Chia Soo
• 金额: $ 133.83万
• 依托单位: SCARLESS LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10474270
• 关键词: Abdomen; Address; Adhesives; Area; Award; Biology; Blood Vessels; Botox; Brain; Businesses; Capital; Cell physiology; Cells; Chemistry; Cicatrix; Clinical; Clinical Research; Clinical Trials; Collagen; Consumption; Cosmetic surgery; Cosmetics; Data; Dermal; Development; Devices; Ensure; FDA approved; Failure; Family suidae; Fascia; Fibroblasts; Fibrosis; Formulation; Gel; Goals; Hernia; Human; Hyaluronic Acid; Hydrogels; Individual; Injectable; Injections; Intellectual Property; Investigational Drugs; Life; Liquid substance; Marketing; Mechanics; Methods; Muscle; Myofibroblast; Operative Surgical Procedures; Peptides; Pharmaceutical Preparations; Phase; Postoperative Complications; Production; Quality of life; Readiness; Reporting; Research Design; Resources; Risk; Safety; Secondary to; Small Business Innovation Research Grant; Structure; Surface; Surgeon; Surgical incisions; Surgical sutures; Tendon structure; Tensile Strength; Therapeutic; Thinness; Time; Tissues; Toxic effect; Viscera; Wound models; base; cell motility; chronic wound; cleft lip and palate; clinical development; commercialization; craniofacial; crosslink; design; disability; fibromodulin; healing; in vivo Model; innovation; migration; mortality; novel; palate repair; preclinical study; product development; programs; psychologic; public health relevance; reconstruction; repaired; safety study; soft tissue; tendon rupture; tissue repair; tool; wound; wound closure; wound healing; wound treatment

PROJECT SUMMARY / ABSTRACT Wounds healing with exuberant fibrotic scarring or wounds that fail to heal represent two opposing ends of the wound repair spectrum. Fibrotic scarring in highly visible areas after craniofacial reconstruction can result in severe functional and cosmetic disability. Similarly, wound dehiscence—wound tissue separation due to a failure to heal with adequate tensile strength—can be life-threatening if it exposes vital structures such as viscera, brain, or blood vessels. Even if non-life-threatening, dehiscence can disrupt critical repairs such as in tendons, hernias, cleft lips and palates (one of the most prevalent congenital craniofacial conditions with post-repair dehiscence rates up to 22.76%). Additionally, ~43% of abdominal incisional hernia cases are secondary to wound dehiscence. More importantly, wound dehiscence mortality rates can be as high as 14%-50%. Unfortunately, all available tissue approximation devices (e.g., sutures, staples, adhesives) only bring tissues together in a purely mechanical fashion. There are no devices to actively promote fibroblast migration and myofibroblast contraction to increase wound tensile strength. To address current device limitations, we developed an SLI-F06 peptide-containing hyaluronic acid (HA) hydrogel (HA-SLI-F06). SLI-F06 promotes fibroblast migration, contraction, and collagen cross-linking to accelerate wound tensile strength reestablishment while HA provides a “bridge” to facilitate cellular migration. An injectable SLI-F06 first-in-class drug is currently in a Phase 1/2a clinical trial to minimize dermal scar formation. However, injecting the liquid SLI-F06 is time- consuming for larger wounds and impractical for thin tissues such as fascia. This PAR-19-333 Commercialization Readiness Pilot (CRP) Program directly continues the Direct-to-Phase II SBIR award R44DE026080, and is designed to accelerate the Clinical Trial Application for the novel bioactive HA-SLI-F06 hydrogel. HA-SLI-F06 can be applied contemporaneously with most any tissue approximation devices during surgery to enhance wound healing. Pig efficacy data showed a significant wound tensile strength increase in wounds treated with HA-SLI-F06 compared to controls. To expedite and derisk technical, regulatory/clinical, and business milestone activities that could impact or delay HA-SLI-F06 commercialization, we propose: AIM 1 to develop the Chemistry, Manufacturing, and Controls (CMC) to minimize technical HA-SLI-F06 production risks; AIM 2 to conduct essential safety studies to support HA-SLI-F06 application in a broad range of soft tissues; AIM 3 to expedite clinical development and minimize regulatory risks by incorporating quantifiable tools to ensure optimal clinical study design and efficient clinical methods to assess safety and efficacy to meet the FDA requirements; and AIM 4 to fully integrate our intellectual property, market focus, and business strategies to maximize valuation. If successful, this product will represent a new paradigm enabling surgeons to easily convert most any mechanical tissue approximation device (e.g., sutures, staples, mesh, adhesives) into a bioactive tissue approximation device to accelerate tensile reestablishment and reduce wound dehiscence, while also decreasing scarring.

项目摘要 /摘要 伤口愈合，良好 伤口修复谱。颅面重建后，在高度可见的区域中的纤维化疤痕可能导致 严重的功能性和化妆品残疾。同样，伤口裂开 - 由于 无法以足够的拉伸强度愈合 - 如果它暴露于内脏等重要结构，会威胁生命 大脑或血管。即使无生命危险，开裂也可能破坏肌腱中的临界维修， 疝气，嘴唇和味觉（最普遍的先天性颅面状况之一 开发率高达22.76％）。此外，〜43％ 伤口开裂。更重要的是，伤口裂开的死亡率可能高达14％-50％。 不幸的是，所有可用的组织近似设备（例如缝合线，钉书钉，粘合剂）仅带来组织 以纯粹的机械方式在一起。没有设备可以积极促进成纤维细胞迁移和 肌纤维细胞合同以增加伤口抗拉强度。为了解决当前的设备限制，我们 开发了含SLI-F06肽的含有肽的氢酸（HA）水凝胶（HA-SLI-F06）。 SLI-F06促进 成纤维细胞迁移，收缩和胶原蛋白交联，加速伤口拉伸强度重建 而HA提供了一个“桥”来促进细胞迁移。当前是一种可注射的SLI-F06一流药物 在第1/2A期临床试验中，以最大程度地减少皮肤疤痕的形成。但是，注射液体sli-f06是时间 - 用于较大的伤口，对于筋膜等薄组织，不切实际。这项标准杆19-333商业化 就绪飞行员（CRP）计划直接继续直接到阶段II SBIR奖R44DE026080，IS 旨在加快新型生物活性HA-SLI-F06水凝胶的临床试验申请。 ha-sli-f06 可以在手术期间与大多数组织近似设备同时应用 伤口愈合。猪效率的数据显示，用 与对照组相比，HA-SLI-F06。加快技术，法规/临床和商业里程碑 可能影响或延迟HA-SLI-F06商业化的活动，我们建议：目标1开发化学， 制造和控制（CMC），以最大程度地降低技术HA-SLI-F06生产风险；瞄准2进行 基本的安全研究，以支持在各种软时范围内应用HA-SLI-F06应用；瞄准3加快 通过合并可量化的工具以确保最佳临床 研究设计和有效的临床方法，以评估满足FDA要求的安全性和有效性；和目标 4要完全整合我们的知识产权，市场重点和业务策略，以最大程度地提高价值。如果 成功，该产品将代表一个新的范式，使外科医生可以轻松转换大多数机械 组织近似装置（例如缝合线，钉书钉，网格，粘合剂）进入生物活性组织近似 加速拉伸重建并减少伤口裂开的设备，同时减少疤痕。