Mechanical Failure Induces a Chronic Wound Phenotype in Laparotomy Incisions

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DESCRIPTION (provided by applicant): Laparotomy incisions fail to heal 11% of the time and progress to incisional hernias. Incisional hernia repairs fail to heal 24-58% of the time. Incisional hernias are now the most common complication of abdominal surgery. Since nearly 4 million laparotomies are performed annually in the US, the incidence of abdominal wall wound failure and incisional hernia formation approaches 400,000. The majority of laparotomy wound failures and incisional hernias occur when there is no indication of a biological wound healing defect. Effected patients were de facto most often considered safe surgical candidates. Instead, we hypothesize that early mechanical laparotomy wound disruption induces a biological defect that is the mechanism for primary and recurrent incisional hernias. This results in a loss of mechanotransduction to abdominal wall tendon repair fibroblasts and the expression of a chronic wound phenotype. In turn, each subsequent incisional hernia repair is more likely to fail. Abdominal wall tendon repair fibroblasts require an optimum load signal to stimulate laparotomy wound repair. It is mechanical wound failure (disruption) that results in the loss of mechanotransduction and impaired wound healing. Our hypothesis therefore is that mechanical strain stimulates early wound healing by abdominal wall tendon fibroblasts. The "tension-free" approach is therefore not consistent with the biology of load-bearing structures. To prove this, we will 1) analyze strain-dependent morphology of laparotomy and hernia wounds using a rat model of laparotomy wound failure and incisional hernia formation, as well as human wound samples 2) determine whether tendon repair fibroblasts derived from mechanically failing laparotomy wounds express a chronic wound phenotype in vitro and 3) attempt to stimulate repair activity in quiescent abdominal wall tendon repair fibroblasts using mechanical strain. Improved laparotomy wound and hernia repair outcomes following abdominal operations may depend on a better understanding of early surgical wound healing. Since the abdominal wall is a load-bearing structure made up of muscles and tendons, load signals may be important for successful abdominal wall repair.