Novel peptide-impregnated hydrogel as a wound healing device

项目总结/摘要 具有旺盛的纤维化瘢痕的伤口愈合或未能愈合的伤口代表了创伤愈合的两个相对端。 创伤修复谱颅面重建后高度可见区域的纤维化瘢痕可导致 严重的功能和外观残疾。同样，伤口裂开-伤口组织分离， 不能以足够的抗张强度愈合-如果它暴露重要的结构如内脏， 大脑或血管。即使不危及生命，裂开也会破坏关键的修复，如肌腱， 疝、唇裂和腭裂（最常见的先天性颅面疾病之一， 开裂率达22.76%。此外，约43%的腹壁切口疝病例继发于 伤口裂开。更重要的是，伤口裂开死亡率可高达14%-50%。 不幸的是，所有可用的组织接近装置（例如，缝合线、斯台普斯、粘合剂）只能将组织 以一种纯粹的机械方式结合在一起。目前还没有积极促进成纤维细胞迁移的装置， 肌成纤维细胞收缩以增加伤口拉伸强度。为了解决当前设备的局限性，我们 开发了含有SLI-F06肽的透明质酸（HA）水凝胶（HA-SLI-F06）。SLI-F06促进 成纤维细胞迁移、收缩和胶原交联以加速伤口拉伸强度重建 而HA则提供了一座促进蜂窝迁移的“桥梁”。目前，一种可注射的SLI-F06一流药物 在1/2a期临床试验中，以最大限度地减少皮肤瘢痕形成。然而，注入液体SLI-F06是时间- 对于较大的伤口是消耗的，而对于薄的组织如筋膜是不实用的。此次PAR-19-333商业化 准备试点（CRP）计划直接延续了直接进入第二阶段SBIR奖R44 DE 026080， 旨在加速新型生物活性HA-SLI-F06水凝胶的临床试验应用。HA-SLI-F06 可以在手术期间与大多数任何组织接近装置同时应用 伤口愈合猪效力数据显示，在用抗张剂处理的伤口中， HA-SLI-F06与对照相比。加快技术、法规/临床和业务里程碑并降低风险 可能影响或延迟HA-SLI-F06商业化的活动，我们建议：AIM 1开发化学， 生产和控制（CMC），以最大限度地降低HA-SLI-F06生产技术风险; AIM 2进行 支持HA-SLI-F06在广泛软组织中应用的基本安全性研究; AIM 3加速 临床开发，并通过纳入可量化的工具来最大限度地降低监管风险，以确保最佳的临床 研究设计和有效的临床方法，以评估安全性和有效性，以满足FDA的要求;和AIM 4.充分整合我们的知识产权、市场焦点和业务策略，以实现估值最大化。如果 成功，该产品将代表一个新的范例，使外科医生能够轻松地转换大多数任何机械 组织接近装置（例如，缝合线、斯台普斯、网片、粘合剂）进入生物活性组织对合 该器械可加速张力重建并减少伤口裂开，同时还可减少瘢痕形成。

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.