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 (HAX(hx)). 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 cm(2), respectively), tPA delivered by HAX(hx) (tPA-HAX(hx)) was highly effective in preventing recurrent adhesions (frequency, 44%; median adhesion area, 0.1cm(2)). HAX(hx) itself, tPA solution, and inactivated tPA in HAX(hx) did not provide comparable anti-adhesion activity. tPA-HAX(hx) is a system that is easy to use and potentially promising for adhesion prevention.
Yeo
Yoon
Y
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Bellas
Evangelia
E
Highley
Christopher B
CB
Langer
Robert
R
Kohane
Daniel S
DS
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005782:Gels; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D023421:Models, Animal; D010532:Peritoneal Diseases / Q000209:etiology / Q000517:prevention & control*; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology; D011183:Postoperative Complications / Q000517:prevention & control; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects
D001672:Biocompatible Materials; D005782:Gels; D006820:Hyaluronic Acid; D010959:Tissue Plasminogen Activator