Mechanical Failure Induces a Chronic Wound Phenotype in Laparotomy Incisions

机械故障导致剖腹手术切口出现慢性伤口表型

• 批准号: 7281730
• 负责人: Michael G Franz
• 金额: $ 27.14万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7281730
• 关键词: Abdomen; Abdominal Injuries; Animal Model; Biological; Biology; Cells; Chronic; Complication; Defect; Disruption; Excision; Failure; Fibroblasts; Growth; Healed; Hernia; Human; Impaired wound healing; In Vitro; Incidence; Intra-abdominal; Laparotomy; Measures; Mechanics; Methods; Modeling; Morphology; Muscle; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Phenotype; Range; Rate; Rattus; Recurrence; Research Design; Research Personnel; Risk; Sampling; Signal Transduction; Site; Structure; Surgical incisions; Surgical wound; Techniques; Tendon Injuries; Tendon structure; Testing; Time; Tissues; United States; Weight-Bearing state; Work; Wound Healing; abdominal wall; bariatric surgery; concept; cost; healing; improved; programs; repaired; wound

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.

描述（申请人提供）：剖腹手术切口不愈合的时间占11%，进展为切口疝。切口疝修复失败率为24-58%。切口疝是目前腹部手术最常见的并发症。由于美国每年有近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。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情况下。事实上，受影响的患者通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导致生物缺陷，这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机械转导的丧失和慢性伤口表型的表达。反过来，每次后续切口疝修补更容易失败。腹壁肌腱修复成纤维细胞需要一个最佳负荷信号来刺激剖腹手术伤口修复。机械性创面失效（断裂）导致机械传导丧失和创面愈合受损。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”方法不符合承重结构的生物学特性。为了证明这一点，我们将1)使用开腹手术伤口失败和切口疝形成的大鼠模型以及人类伤口样本分析剖腹手术和疝伤口的应变依赖形态2)确定机械失败的剖腹手术伤口衍生的肌腱修复成纤维细胞是否在体外表达慢性伤口表型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。腹部手术后切口和疝修复效果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，因此负荷信号对于腹壁的成功修复可能很重要。