Development of carboxymethyl cellulose/gelatin hybrid hydrogels via radiation-induced cross-linking as novel anti-adhesion barriers

Abstract

Adhesion after abdominal and pelvic surgery results in severe clinical outcomes and a negative impact on the quality of life of a patient. Implanting barrier materials is a common strategy for preventing postoperative adhesion, and non-adhesive carboxymethylcellulose (CMC) is a widely used material for such purpose. Herein, we present CMC/gelatin (CMC/G) hybrid hydrogels as novel barrier materials that aim to reduce the foreign body response (FBR) by combining the biocompatibility and biodegradability of gelatin and the non-adhesiveness of CMC and by realizing mechanical matching with the host tissue. The hydrogels were prepared by the simple reagent-free γ-ray irradiation-induced cross-linking of CMC and gelatin. The hydrogel composition was controlled by varying the initial mixing ratio. The gelatin fraction provided enzyme-mediated degradability at a content ≥ 40%, and the degradation rate was controlled by the radiation dose. The compressive moduli of the hydrogels were tuned to be identical to that of target abdominal organs (several tens of kPa) via 10–30 kGy radiation. The hydrogels sufficiently prevented adhesion of 3T3-Swiss fibroblast cells owing to the non-adhesive capability of CMC which surpassed the high cell adhesiveness of gelatin in the hydrogels. On the other hand, the added gelatin significantly improved the viability of the few cells that adhered to the hydrogels. We found that hydrogels composed of 60% CMC and 40% gelatin exhibited significantly higher cell viabilities while maintaining the non-adhesiveness which is desirable as barrier materials. The in vitro assessments demonstrated the potential of the hydrogel as a novel barrier material with excellent biocompatibility, wound healing promoting effect, and FBR reducing effect by realizing mechanical matching with the host abdominal organs, especially when it was composed of 60% CMC and 40% gelatin and cross-linked at 10–30 kGy to impart compressive modulus of 20–100 kPa.