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: 7394621
• 负责人: PAUL T HAMILTON
• 金额: $ 28.75万
• 依托单位: AFFINERGY ,INC
• 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 2009-08-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7394621
• 关键词: Abdomen; Address; Affinity; Area; Attention; Binding; Biocompatible Materials; Biological; Caring; Cell Proliferation; Cells; Characteristics; Chemistry; Collagen; Dermis; Devices; Distress; Engineering; Failure; Fascia; Foreign Bodies; Goals; Growth; Growth Factor; Healed; Hernia; Human; In Vitro; Inpatients; Left; Link; Localized; Mediating; Medical Device; Metals; Operative Surgical Procedures; Patients; Peptides; Phage Display; Pharmaceutical Preparations; Phase; Physicians; Plastics; Platelet-Derived Growth Factor; Population; Postoperative Period; Probability; Procedures; Process; Proteins; Quality of Care; Range; Rate; Recurrence; Relative (related person); Repair Material; Repeat Surgery; Safety; Signal Transduction; Site; Solutions; Specificity; Surface; Surgeon; Surgical Mesh; Suture Techniques; System; Techniques; Technology; Testing; Therapeutic; Time; Tissues; To specify; United States; Ursidae Family; Use of New Techniques; Wound Healing; aqueous; base; cost; critical developmental period; crosslink; design; extracellular; follow-up; healing; improved; in vivo; interfacial; novel; novel therapeutics; platelet-derived growth factor BB; programs; protein aminoacid sequence; repaired; response; soft tissue

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.

描述(由申请人提供)：在美国，每年有超过700,000例腹股沟疝修补术，尽管最近取得了进展，但复发率仍然很高。在疝修补术中，使用生物可兼容网片来加强腹筋膜在很大程度上已经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片，它可以承受永久性异物的所有缺陷；或者其他胶原基网片，它可以被生物吸收，但失败率高得令人无法接受，会导致复发的疝气。因此，外科医生只能选择异物或软弱的修复。我们的目标是改进现有的生物材料，以缩短从最初修复到内源性伤口愈合之间的关键时期，减少复发疝气的可能性。疝修补术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体与无效的靶向策略相结合。我们在这里提出了一个多肽连接系统，它结合了两个基于胶原的修复网(无细胞人真皮[MTF]，CollaMend[Davol]等)。和生长因子，转化生长因子和PDGF已知促进关键的伤口愈合过程。利用噬菌体展示技术，我们将分离选择性结合转化生长因子-BB和血小板衍生生长因子-BB的多肽序列(特异性靶标I)。然后，我们将在这些多肽和AffinEnergy现有的胶原结合序列(特定目标II)之间设计一个连接体，并最终确定双功能界面生物材料(IFBMs；特定目标III)的体外功效。我们的定向生长因子交付策略旨在减少修复失败的最常见时间窗口，进而减少住院后续护理、额外手术和患者痛苦。尽管手术技术和新的修补材料的使用发生了变化，但手术修复后的腹股沟复发在统计学上仍然是不变的。生物制剂是一种潜在的解决方案，但由于缺乏传递机制，在软组织手术中仍未得到充分利用。这项建议旨在开发一种新的多肽连接系统，以非共价方式将生长因子结合到以胶原为基础的外科修复网上。我们正试图将生物修复机制引导到手术修复部位。疝修补术是世界上最常见的外科手术之一。减少重复手术、术后医生的关注和治愈时间将提高数十万患者的护理成本和质量。