Ibuprofen-loaded bilayer electrospun mesh modulates host response toward promoting full-thickness abdominal wall defect repair.

ABSTRACT

Pro-inflammatory response impairs the constructive repair of abdominal wall defects after mesh implantation. Electrospinning-aid functionalization has the potential to improve the highly orchestrated response by attenuating the over-activation of foreign body reactions. Herein, we combined poly(L-lactic acid-co-caprolactone) (PLLA-CL) with gelatin proportionally via electrospinning, with Ibuprofen (IBU) incorporation to fabricate a bilayer mesh for the repair improvement. The PLLA-CL/gelatin/IBU (PGI) mesh was characterized in vitro and implanted into the rat model with a full-thickness defect for a comprehensive evaluation in comparison to the PLLA-CL/gelatin (PG) and off-the-shelf small intestinal submucosa (SIS) meshes. The bilayer PGI mesh presented a sustained release of IBU over 21 days with degradation in vitro and developed less-intensive intraperitoneal adhesion along with a histologically weaker inflammatory response than the PG mesh after 28 days. It elicited an M2 macrophage-dominant foreign body reaction within the process, leading to a pro-remodeling response similar to the biological SIS mesh, which was superior to the PG mesh. The PGI mesh provided preponderant mechanical supports over the SIS mesh and the native abdominal wall with similar compliance. Collectively, the newly developed mesh advances the intraperitoneal applicability of electrospun meshes by guiding a pro-remodeling response and offers a feasible functionalization approach upon immunomodulation.