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: 10689794
• 负责人: Chia Soo
• 金额: $ 107.71万
• 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/10689794
• 关键词: Abdomen; Acceleration; 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; Good Manufacturing Process; 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; 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; cell motility; chronic wound; cleft lip and palate; clinical development; commercialization; commercialization readiness; comparison control; craniofacial; crosslink; design; disability; fibromodulin; healing; in vivo Model; innovation; manufacture; migration; mortality; novel; palate repair; preclinical study; product development; programs; psychologic; public health relevance; reconstruction; repaired; safety assessment; 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.

项目概要/摘要 具有丰富纤维化疤痕的伤口愈合或无法愈合的伤口代表了伤口的两端 伤口修复谱。颅面重建后高度可见区域的纤维化疤痕可能会导致 严重的功能和外观缺陷。类似地，伤口裂开——由于某种原因导致的伤口组织分离。 未能以足够的抗拉强度愈合——如果暴露重要结构，如内脏、 大脑，或者血管。即使不危及生命，裂开也会破坏关键的修复，例如肌腱、 疝气、唇裂和腭裂（修复后最常见的先天性颅面疾病之一） 开裂率高达22.76%）。此外，约 43% 的腹部切口疝病例继发于 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，所有可用的组织逼近装置（例如缝合线、钉书钉、粘合剂）仅携带组织 以纯粹机械的方式结合在一起。没有装置可以主动促进成纤维细胞迁移和 肌成纤维细胞收缩以增加伤口的抗拉强度。为了解决当前设备的限制，我们 开发了一种含有 SLI-F06 肽的透明质酸 (HA) 水凝胶 (HA-SLI-F06)。 SLI-F06促销 成纤维细胞迁移、收缩和胶原交联加速伤口拉伸强度重建 而HA则提供了促进细胞迁移的“桥梁”。注射用SLI-F06一流药物目前正在研发中 正在进行 1/2a 期临床试验，以尽量减少真皮疤痕的形成。然而，注入液体SLI-F06是时间- 对于较大的伤口来说消耗很大，对于筋膜等薄组织来说不切实际。本 PAR-19-333 商业化 准备试点 (CRP) 计划直接延续直接进入第二阶段 SBIR 奖项 R44DE026080，并且 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组织挤压装置同时应用，以增强 伤口愈合。猪功效数据显示，经处理的伤口的伤口拉伸强度显着增加 HA-SLI-F06 与对照相比。加快技术、监管/临床和业务里程碑的进程并消除风险 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， 制造和控制 (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 加快 通过结合可量化的工具来确保最佳的临床开发，并最大限度地降低监管风险 研究设计和有效的临床方法来评估安全性和有效性以满足 FDA 的要求；和目标 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范例，使外科医生能够轻松转换大多数机械 将组织逼近装置（例如缝合线、钉书钉、网片、粘合剂）转化为生物活性组织逼近 加速张力重建和减少伤口裂开的装置，同时也减少疤痕。

项目成果

Fibromodulin reduces scar formation in adult cutaneous wounds by eliciting a fetal-like phenotype.

• DOI: 10.1038/sigtrans.2017.50
• 发表时间: 2017
• 期刊: Signal transduction and targeted therapy
• 影响因子: 39.3
• 作者: Zheng Z;James AW;Li C;Jiang W;Wang JZ;Chang GX;Lee KS;Chen F;Berthiaume EA;Chen Y;Pan HC;Chen EC;Li W;Zhao Z;Zhang X;Ting K;Soo C
• 通讯作者: Soo C

Fibromodulin reprogrammed cells: A novel cell source for bone regeneration.

• DOI: 10.1016/j.biomaterials.2016.01.013
• 发表时间: 2016-03
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Li CS;Yang P;Ting K;Aghaloo T;Lee S;Zhang Y;Khalilinejad K;Murphy MC;Pan HC;Zhang X;Wu B;Zhou YH;Zhao Z;Zheng Z;Soo C
• 通讯作者: Soo C

Fibromodulin reduces scar size and increases scar tensile strength in normal and excessive-mechanical-loading porcine cutaneous wounds.

• DOI: 10.1111/jcmm.13516
• 发表时间: 2018-04
• 期刊: Journal of cellular and molecular medicine
• 影响因子: 5.3
• 作者: Jiang W;Ting K;Lee S;Zara JN;Song R;Li C;Chen E;Zhang X;Zhao Z;Soo C;Zheng Z
• 通讯作者: Zheng Z

Bioactive wound Closure Devices are highly Demanded.

生物活性伤口闭合装置的需求量很大。

• 发表时间: 2018
• 期刊: Clinics of surgery
• 作者: Ha,Pin;Golnazarian,NicoletteK;Soo,Chia;Zheng,Zhong
• 通讯作者: Zheng,Zhong