Peritoneal adhesion prevention with an in situ cross-linkable hyaluronan gel containing tissue-type plasminogen activator in a rabbit repeated-injury model

Postoperative peritoneal adhesions can have serious, potentially lethal consequences. Pharmacotherapy and barrier devices can reduce adhesion formation to varying degrees, but their efficacy is limited by rapid clearance from the peritoneum and lack of biological activity, respectively. To overcome these limitations, we have delivered tissue-type plasminogen activator (tPA), which is deficient in the first 2–3 postoperative days, using a highly cross-linked in situ forming hyaluronan gel (HAXhx). We demonstrated this formulation's anti-adhesion activity in a rigorous animal model that involved recurrent adhesions. While non-treated or saline-treated animals developed widespread adhesions (frequency, both 100%; median adhesion area, 12.7 and 15.4 cm2, respectively), tPA delivered by HAXhx (tPA-HAXhx) was highly effective in preventing recurrent adhesions (frequency, 44%; median adhesion area, 0.1 cm2). HAXhx itself, tPA solution, and inactivated tPA in HAXhx did not provide comparable anti-adhesion activity. tPA-HAXhx is a system that is easy to use and potentially promising for adhesion prevention.