Localized Growth Factor Therapy for Surgical Hernia Repair

用于疝气修复手术的局部生长因子疗法

• 批准号: 8499488
• 负责人: Bruce Lamb
• 金额: $ 107.77万
• 依托单位: AFFINERGY, LLC
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-14 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8499488
• 关键词: Localized; Growth; Factor; Therapy; Surgical

DESCRIPTION (provided by applicant): Over 700,000 surgical hernia repairs are performed each year in the United States and despite recent advances, a significant rate of recurrence persists. The incorporation of biocompatible mesh to strengthen the abdominal fascia has largely replaced high-tension suturing techniques in hernia repair. Currently, the preferred biomaterials include durable synthetic mesh, which bears all the pitfalls of a permanent foreign body; or other collagen-based meshes, which are bioabsorbable but fail at an unacceptably high rate causing recurrent hernias. Surgeons are therefore left to choose either a foreign body or a weak repair. Our goal is to apply our site-specific delivery technology toward the improvement of current biomaterials, shortening the critical period between initial repair, and endogenous wound healing. Using phage display technology, we have isolated peptide sequences which selectively bind PDGF-BB and TGF-¿3 and collagen-based surgical repair materials with sub-micromolar relative affinity as synthetic peptides. During our Phase I research program, we have linked these peptides to generate a bifunctional molecule, capable of localized retention of biologically active doses of growth factor on the surface of collagen-based mesh materials. The technology presented here provides a unique means of sustaining the retention and delivery of growth factors to a surgical site, without altering the structural composition of collagen-based resorbable hernia repair mesh. The proposed Phase II research plan will continue the commercialization of our leading PDGF-BB:collagen peptide as a coating for collagen-based repair mesh. The TGF-¿3:collagen peptide will be put through a similar battery of tests and optimization efforts during a follow-up product development plan. First, we will employ our extensive experience in peptide chemistry and sequence optimization to devise an efficient pilot-scale peptide synthesis strategy capable of generating > 500 mg of peptide per batch. In parallel with these synthesis efforts, testing will begin on Affinergy's PDGF:collagen binding peptide using autologously harvested sources of growth factor, such as platelet rich plasma. Success in these efforts would remove any future need for a partner with proprietary rights to a recombinant growth factor. The PDGF-BB:collagen and peptide will then be subjected to the battery of biocompatibility testing required for regulatory approval. Peptide will also be examined for stability and function after simulated long-term storage and after exposure widely-used sterilization technique(s). Finally, a rodent model for soft tissue healing after mesh implantation will be used to establish both pharmacokinetics and wound healing rates using peptide-delivered PDGF-BB on collagen repair mesh. These data will provide the first evidence for in vivo efficacy of our peptide, and will be essential for regulatory submissions and partnership development. We feel that the proposed Phase II research plan accelerates the entrance of this product to market, refreshes our product pipeline and extends our core capabilities into critical areas for our continued growth as an innovative medical technology company. PUBLIC HEALTH RELEVANCE: Improving the rate of healing after surgical hernia repair would reduce pain, discomfort and follow-up care. The introduction of biologics into soft tissue healing represents a potential improvement, but due to a lack of clinically viable delivery mechanisms, these molecules remain under-utilized. This proposal aims to further the commercialization of a novel peptide linkage system for the local retention of growth factors on a collagen-based surgical repair mesh. We believe that this primary product concept has the potential to enhance healing after surgical hernia repair by adding growth factors to collagen meshes without altering their desireable properties. However, we also seek to extend our technology to the use of autologous growth factors from platelet rich plasma, to provide partnership flexibility, and accelerate our route to market. Because hernia repair is one of the most common surgical procedures world-wide, this product will provide substantially improved clinical outcomes. .

描述（由申请人提供）：在美国，每年有超过70万例手术疝修补，尽管最近取得了进展，但复发率仍然很高。在疝修补中，生物相容性补片强化腹筋膜已在很大程度上取代了高压缝合技术。目前，首选的生物材料包括耐用的合成网，它承担了永久性异物的所有缺陷；或者其他基于胶原蛋白的补片，它们是生物可吸收的，但失败率高得令人无法接受，导致复发性疝气。因此，外科医生只能选择异物或弱修复。我们的目标是将我们的位点特异性递送技术应用于现有生物材料的改进，缩短初始修复和内源性伤口愈合之间的关键时期。利用噬菌体展示技术，我们分离出选择性结合PDGF-BB和TGF-¿3以及具有亚微摩尔相对亲和力的胶原基手术修复材料的肽序列作为合成肽。在I期研究项目中，我们将这些肽连接起来，生成了一种双功能分子，能够在胶原基网状材料表面局部保留生物活性剂量的生长因子。本文介绍的技术提供了一种独特的方法来维持生长因子的保留和输送到手术部位，而不改变胶原基可吸收疝修补网的结构组成。拟议的II期研究计划将继续商业化我们领先的PDGF-BB：胶原肽作为胶原基修复网的涂层。TGF-¿3：胶原蛋白肽将在后续产品开发计划中进行类似的一系列测试和优化工作。首先，我们将利用我们在多肽化学和序列优化方面的丰富经验，设计一种高效的中试多肽合成策略，每批多肽能产生50 - 500毫克。与这些合成工作同时，affinenergy的PDGF（胶原结合肽）的测试也将开始，测试使用的是自体收集的生长因子，比如富含血小板的血浆。这些努力的成功将消除未来对拥有重组生长因子专有权利的合作伙伴的任何需求。然后，PDGF-BB胶原蛋白和肽将进行一系列生物相容性测试，以获得监管部门的批准。在模拟长期储存和暴露于广泛使用的灭菌技术后，还将检查肽的稳定性和功能。最后，我们将利用一种啮齿类动物的网状物植入后软组织愈合模型来建立肽递送的PDGF-BB在胶原修复网状物上的药代动力学和伤口愈合率。这些数据将为我们的肽的体内疗效提供第一个证据，并将对监管申请和合作伙伴关系发展至关重要。我们认为，拟议的二期研究计划加速了该产品进入市场，更新了我们的产品线，并将我们的核心能力扩展到关键领域，以促进我们作为一家创新型医疗技术公司的持续增长。