Injectable nanoengineered adhesive hydrogel for treating enterocutaneous fistulas

Abstract

Enterocutaneous fistula (ECF) is a severe medical condition where an abnormal connection forms between the gastrointestinal tract and skin. ECFs are, in most cases, a result of surgical complications such as missed enterotomies or anastomotic leaks. The constant leakage of enteric and fecal contents from the fistula site leads to skin breakdown and increases the risk of infection. Despite advances in surgical techniques and postoperative management, ECF accounts for significant mortality rates, estimated between 15 and 20 %, and causes debilitating morbidity. Therefore, there is a critical need for a simple and effective method to seal and heal ECFs. Injectable hydrogels with combined properties of robust mechanical properties and cell infiltration/proliferation have the potential to block and heal ECFs. Herein, we report the development of an injectable nanoengineered adhesive hydrogel (INAH) composed of a synthetic nanosilicate (Laponite®) and a gelatin-dopamine conjugate for treating ECFs. The hydrogel undergoes fast cross-linking using a co-injection method, resulting in a matrix with improved mechanical and adhesive properties. INAH demonstrates appreciable blood clotting abilities and is cytocompatible with fibroblasts. The adhesive properties of the hydrogel are demonstrated in ex vivo adhesion models with skin and arteries, where the volume stability in the hydrated internal environment facilitates maintaining strong adhesion. In vivo assessments reveal that the INAH is biocompatible, supporting cell infiltration and extracellular matrix deposition while not forming fibrotic tissue. These findings suggest that this INAH holds promising translational potential for sealing and healing ECFs. Statement of significance: This research manuscript presents a groundbreaking INAH for treating ECFs. The INAH, composed of a synthetic nanosilicate and gelatin-dopamine conjugate, offers versatile implications in tissue regeneration and localized drug delivery. Acting as a scaffold, the shear-thinning hydrogel enables easy injection, forming a stable structure that supports tissue regeneration and integrates with surrounding tissues. By incorporating bioactive cues, it guides cell behavior and promotes functional tissue regeneration. The INAH also demonstrates potential for localized drug delivery, releasing therapeutic agents over time to enhance efficacy and minimize side effects. This research showcases INAH as a promising solution for ECFs, with applications in tissue engineering and regenerative medicine, marking a significant advancement in the field.