Localized Growth Factor Therapy for Surgical Hernia Repair

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 abdomi nal 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 bio absorbable 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 strate gies. 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 technol ogy, 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 sur geries 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 m echanisms, 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.