Mechanical Failure Induces a Chronic Wound Phenotype in Laparotomy Incisions

描述（由申请人提供）：11%的剖腹手术切口无法愈合，并进展为切口疝。切口疝修补术有24-58%的时间无法愈合。切口疝现在是腹部手术最常见的并发症。由于美国每年进行近400万例剖腹手术，腹壁伤口失败和切口疝形成的发生率接近40万例。大多数剖腹手术伤口失败和切口疝发生在没有生物伤口愈合缺陷的迹象时。受影响的患者实际上最常被认为是安全的手术候选人。相反，我们假设早期机械性剖腹手术伤口破裂引起的生物学缺陷是原发性和复发性切口疝的机制。这导致腹壁肌腱修复成纤维细胞的机械转导损失和慢性伤口表型的表达。反过来，每次随后的切口疝修补术更有可能失败。腹壁肌腱修复成纤维细胞需要一个最佳的负载信号来刺激剖腹手术伤口修复。机械性伤口失效（破坏）导致机械传导丧失和伤口愈合受损。因此，我们的假设是，机械应变刺激腹壁肌腱成纤维细胞的早期伤口愈合。因此，“无张力”方法与承重结构的生物学不一致。为了证明这一点，我们将1）使用剖腹手术伤口失败和切口疝形成的大鼠模型分析剖腹手术和疝伤口的应变依赖性形态学，2）确定源自机械失效的剖腹手术伤口的肌腱修复成纤维细胞是否在体外表达慢性伤口表型，以及3）尝试使用机械应变刺激静止腹壁肌腱修复成纤维细胞的修复活性。腹部手术后剖腹手术伤口和疝修补术结局的改善可能取决于对早期手术伤口愈合的更好理解。由于腹壁是由肌肉和肌腱组成的承重结构，因此载荷信号对于成功的腹壁修复可能是重要的。

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.