Localized Growth Factor Therapy for Surgical Hernia Repair

描述（由申请人提供）：美国每年进行超过700，000例疝修补手术，尽管最近取得了进展，但复发率仍然很高。在疝修补术中，采用生物相容性补片加强腹部筋膜已在很大程度上取代了高张力疝修补技术。目前，优选的生物材料包括耐用的合成补片，其承受永久性异物的所有缺陷;或其他胶原基补片，其是生物可吸收的，但以不可接受的高比率失效，导致复发性疝。因此，外科医生只能选择异物或弱修复。我们的目标是改进目前的生物材料，以缩短初始修复和内源性伤口愈合之间的关键期，降低疝复发的可能性。疝修补的生物学方法尚未站稳脚跟，部分原因是筋膜组织中的异质细胞群与无效的靶向策略相结合。我们在这里提出了一种结合胶原基修复网（无细胞人真皮[MTF]，CollaMend [Davol]等）和生长因子，TGF-和PDGF已知促进关键，伤口愈合过程。使用噬菌体展示技术，我们将分离选择性结合TGF-β和PDGF-BB（特异性Aim I）的肽序列。然后，我们将在这些肽和Affinergy现有的胶原蛋白结合序列（Specific Aim II）之间设计一个接头，并最终确定双功能界面生物材料（IFBM; Specific Aim III）的体外功效。我们有针对性的生长因子输送策略旨在减少修复失败的最常见时间窗口，从而减少住院随访护理，额外手术和患者痛苦。 尽管手术技术发生了变化，并使用了新的修补材料，但手术修补后疝复发率在统计学上保持不变。生物制剂是一种潜在的解决方案，但由于缺乏输送机制，在软组织手术中仍然没有得到充分利用。该提案旨在开发一种新的肽连接系统，以将生长因子非共价结合到基于胶原蛋白的外科修复网。我们正试图引导生物愈合机制向手术修复部位发展。疝修补术是世界范围内最常见的外科手术之一。减少重复手术，术后医生的关注和愈合时间将改善数十万患者的护理成本和质量。

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 biocompatable 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 fails 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 improve current biomaterials to shorten the critical period between initial repair and endogenous wound healing, reducing the probability of a recurring hernia. Biological approaches to hernia repair have not yet gained a foothold, due in part to the heterogeneous cell populations in fascial tissue combined with ineffective targeting strategies. We propose here, a peptide linkage system that binds both collagen-based repair meshes (acellular human dermis [MTF], CollaMend [Davol] etc.) and growth factors, TGF- and PDGF known to promote key, wound-healing processes. Using phage display technology, we will isolate peptide sequences which selectively bind TGF- and PDGF-BB (Specific Aim I). We will then engineer a linker between these peptides and Affinergy's existing collagen-binding sequences (Specific Aim II) and finally determine the in vitro efficacy of the bifunctional interfacial biomaterials (IFBMs; Specific Aim III). Our targeted growth factor delivery strategy is designed to reduce the most common time window for repair failures and in turn, reduce inpatient follow-up care, additional surgeries and patient distress. Hernia recurrence after surgical repair has remained statistically immutable despite changes in surgical techniques and the use of new repair materials. Biologics represent a potential solution, but due to a lack of delivery mechanisms, remain underutilized in soft tissue procedures. This proposal aims to develop a novel peptide linkage system to non-covalently bind growth factors to a collagen-based surgical repair mesh. We are attempting to guide biological healing mechanisms toward surgical repair sites. Hernia repair is one of the most common surgical procedures world-wide. Reducing repeat surgeries, post-operative physician attention and healing time would improve both the cost and quality of care for hundreds of thousands of patients.