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，每年进行700,000多个手术疝修理，尽管最近进展，但复发率仍然很高。掺入可增强腹部筋膜的生物相容性网状网已在很大程度上取代了疝气修复中的高度缝合技术。当前，首​​选的生物材料包括耐用的合成网，它具有永久异物的所有陷阱。或其他基于胶原蛋白的网格，可生物吸收，但以不可接受的高速率失败，导致复发性疝气。因此，外科医生可以选择异物或弱修复。我们的目标是改善当前的生物材料，以缩短初始修复和内源性伤口愈合之间的关键时期，从而降低反复疝的可能性。生物学修复的生物学方法尚未立足，部分原因是筋膜组织中的异质细胞种群以及无效的靶向策略结合在一起。我们在这里提出，这是一种结合基于胶原蛋白的修复网格（细胞人类真皮[MTF]，Collamend [Davol]等）和生长因子，TGF-和PDGF已知促进密钥伤口控制过程的生长因子。使用噬菌体显示技术，我们将隔离肽序列，这些肽序列有选择地结合TGF-和PDGF-BB（特定的AIM I）。然后，我们将在这些肽和Affinergy现有的胶原结合序列（特定的AIM II）之间设计一个接头，并最终确定双功能界面生物材料的体外功效（IFBMS；特定AIM III）。我们的目标生长因子输送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，额外的手术和患者困扰。 尽管手术技术发生了变化和使用新的维修材料，但手术修复后的疝气复发仍然在统计上不变。生物制剂代表了潜在的解决方案，但由于缺乏递送机制，在软组织程序中仍未充分利用。该提案旨在开发一种新型的肽连锁系统，以非共价结合生长因子与基于胶原蛋白的手术修复网格。我们试图将生物愈合机制引导到手术修复部位。疝气修复是全球最常见的外科手术之一。减少重复手术，术后医生的关注和康复时间将改善数十万患者的成本和护理质量。