Novel peptide-impregnated hydrogel as a wound healing device

项目摘要/摘要 创面愈合时伴有旺盛的纤维性瘢痕或无法愈合的创面代表着创面的两端。 伤口修复光谱。颅面重建后高可见区域的纤维性瘢痕可导致 严重的功能和美容残疾。同样，伤口裂开-伤口组织分离由于 不能以足够的抗张强度愈合-如果暴露出重要的结构，如内脏，可能会危及生命， 脑部，或血管。即使没有生命危险，断裂也会扰乱关键的修复，比如肌腱的修复， 疝气、唇裂和腭裂(修复后最常见的先天性头面部疾病之一 裂孔率高达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，所有可用的组织近似设备(例如，缝合线、缝合器、粘合剂)只带来组织 以一种纯粹的机械方式聚集在一起。没有设备可以积极促进成纤维细胞的迁移和 肌成纤维细胞收缩以增加伤口的抗张强度。为了解决当前的设备限制，我们 研制了SLI-F06多肽透明质酸(HA)水凝胶(HA-SLI-F06)。SLI-F06推广 成纤维细胞迁移、收缩和胶原交联加速伤口抗张强度重建 而HA为促进细胞迁移提供了一座“桥梁”。一种可注射的SLI-F06一级药物目前 在1/2a期临床试验中，以尽量减少皮肤疤痕的形成。然而，注入液体SLI-F06是时间- 对于较大的伤口是消耗，而对于筋膜等薄组织是不切实际的。此标准杆19-333商业化 就绪性试点(CRP)计划直接延续直接到第二阶段SBIR奖励R44DE026080， 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 可在手术中与几乎任何组织近似设备同时应用，以增强 伤口愈合。猪的疗效数据显示，处理后伤口的抗张强度显著增加。 HA-SLI-F06与对照组的比较。加快和降低技术、法规/临床和业务里程碑 可能影响或推迟HA-SLI-F06商业化的活动，我们建议：目标1发展化学， 制造和控制(CMC)，以将技术HA-SLI-F06生产风险降至最低；AIM 2进行 基本安全性研究，以支持HA-SLI-F06在广泛的软组织中的应用；AIM 3，以加快 通过整合可量化的工具来确保最佳临床开发，并将监管风险降至最低 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； 4充分整合我们的知识产权、市场焦点和业务战略，以实现估值最大化。如果 成功后，该产品将代表一种新的范例，使外科医生能够轻松地将几乎任何机械设备 组织近似装置(例如，缝合线、缝合器、网状物、粘合剂)形成生物活性组织近似 该装置可加速张力重建，减少伤口裂开，同时还可减少疤痕。

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.