Addition of nimesulide to small intestinal submucosa biomaterial inhibits postsurgical adhesiogenesis in rats

Abstract

Adhesion formation is a common complication in abdominal surgery with incidence as high as 93% and small bowel obstruction a common complication. Because the extracellular matrix material, small intestinal submucosa (SIS), is commonly used in various surgical procedures, methods to inhibit adhesiogenesis are of great interest. This study was undertaken to determine if incorporation of nimesulide (NM), a selective cyclooxygenase (COX)-2 inhibitor, could reduce the extent and tenacity of intraabdominal adhesion formation associated with SIS implantation. Female Sprague-Dawley rats underwent a cecal abrasion surgical procedure to induce adhesiogenesis. Rats were either left untreated or treated by direct application over the injured cecum with polypropylene mesh (PPM); SIS; SIS containing a low dose of NM; or SIS containing a high dose of NM. Rats were euthanized 21 days later, and adhesion extent and tenacity were evaluated using standard scales (0 = minimal adhesiogenesis; 4 = severe adhesiogenesis). Addition of NM to SIS resulted in a significant (p < 0.05) reduction in adhesion extent and in a similar reduction in adhesion tenacity for SIS containing a low dose of NM. Adhesions typically extended from the abraded cecal surface to the body wall and were characterized histologically by fibrous tissue adherent to the cecal wall. In conclusion, addition of the nonsteroidal anti-inflammatory, COX-2 selective drug, NM, to SIS attenuates adhesion extent and tenacity when compared with surgical placement of SIS or PPM alone.

Encapsulation of cell‐adhesive RGD peptides into a polymeric physical hydrogel to prevent postoperative tissue adhesion

“…In general, there are two anti‐adhesion strategies: (1) pharmaceutical treatments5, 6 and (2) barrier‐based devices 7–10. To prevent tissue adhesion, a number of bioactive substances such as anti‐inflammatory agents11, 12 and fibrinolytic agents5, 13 have been tried. Pharmaceutical treatments alone do not prevent adhesions very effectively due to the rapid loss of drugs from the peritoneum, and thus sustained release is required.…”

“…On the other hand, barrier devices, such as polymer films and hydrogels,14–21 play important roles in antiadhesion. The above two strategies could be used simultaneously 11, 13, 22…”

Histological and Immunohistological Evaluation of the Tissue Response of a New Barrier Material Based on D,L-Polylactide, Trimethylene Carbonate and Caprolactone to Prevent Peritoneal Adhesion Formation

“…Taking these findings together, on the one hand SupraSeal ® seems not to increase the inflammatory response, indicating good tissue compatibility of this material. On the other hand, the significant reduction of adhesion formation by SupraSeal ® without differences in the extent of inflammation compared to the control samples indicates that an anti-inflammatory strategy in adhesion prevention, as recommended by some authors, should be viewed with caution [36][37][38][39]. On this issue, the role of the inflammatory response in adhesion formation as well as the proper time point for any antiinflammatory strategies in case of their implementation in adhesion prevention should be investigated in further prospective experimental studies.…”

An injectable hydrogel derived from small intestine submucosa as a stem cell carrier

“…6,7 Small intestine submucosa (SIS) is derived from the porcine jejunum, which consists of decellularized ECM, including primarily (>90%) collagen type I, II, III, and various kinds of bioactive factors such as basic fibroblast growth factor (bFGF), transforming growth factor-b (TGF-b), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), glycosaminoglycans, fibronectins, chondroitin sulfates, heparins, heparin sulfates, and hyaluronic acids. [8][9][10][11][12][13][14][15][16][17][18][19] Several approaches have demonstrated that SIS biomaterials promote constructive remodeling in body tissues, including the bone, 8 skin, 9 vocal cord, 10 oesophageal tissue, 11,12 blood vessels, 13 biliary tract, 14 tunica albuginea, 15 kidney, 16 ureter, 17 abdominal wall. 18,19 Although there have been many approaches in SIS studies with significant advances over the past few decades, to our knowledge, studies on SIS-based injectable hydrogels in vivo are scarce.…”