Grants We Funded

Abstract
Clinical studies demonstrate that 10-11 % of all abdominal wall closures fail to heal, leading to incisional hernia formation. This failure to heal results in approximately 200,000 incisional hernia repairs performed each year in the United States.2 Despite technically adequate repairs, recurrent incisional hernia formation is common. Prospective randomized studies that compared the outcomes of suture and mesh herniorraphy found that the incidence of recurrent incisional hernia formation was 43% after standard suture repair and decreased to 23% with implant of a mesh prosthesis. Despite increased prosthesis utilization with hernia repair in the modem clinical era, mesh has an increased risk of serious complications and significant recurrence rates. Synthetic materials to date still have inadequate incorporation, remodeling, and long-term stability often leading to late mechanical failure. Biocompatible acellularized materials such as Alloderm have recently become popular but hold many disadvantages such as immunogenic reactions, infectious transmissions, slow remodeling, and variable success. Due to the limited intrinsic capabilities of "conventional" prostheses and synthetic material, we propose using acellularized myofascial (AM) constructs tissue engineered in our own lab for abdominal wall reconstruction and incisional hernia repair. Tissue prostheses should mimic "native" abdominal wall physiology that is have high compliance, low stiffness, submaximal breaking strength, and high biocompatibility7. The purpose of this study is to develop and characterize a new scaffold based on AM construct material seeded with autologous dermal fibroblasts in cell culture thus tissue engineering of a "new" abdominal wall construct. In theory, fibroblasts in the short term might improve extracellular matrix deposition and local cell recruitment and in the long term they would influence scaffold resorption and remodeling. This study will determine the physical and biological properties of AM constructs in comparison to mesh, will formally evaluate their utility for incisional hernia repair, and will establish a rational basis directed at developing AM constructs for future large-animal and clinical studies. We propose that AM constructs with fibroblasts have BOTH 1) better mechanical compliance matching to native abdominal wall AND 2) allow cellular ingrowth. The primary outcome variable for this experiment is the hernia recurrence rate. In this proposal, patented acellularization methods are employed and allografts are tissue engineered from rat abdominal walls to decrease immune reactions. The technique allows preservation of the collagenous matrix to maintain long term mechanical strength allowing repopulation and remodeling of the grafts by ingrowing cells. We use an established rat "giant" incisional hernia model8 in which the laparotomies reliably progress to form incisional hernias. When used as a tissue prosthesis for incisional hernias, acellularized myofascial (AM) constructs impregnated with fibroblasts result in reduced recurrence rates compared to alloplastic mesh or AM constructs alone.