Injectable hydrogels based on polyethylene glycol and chitosan derivatives with wet tissue adhesion for promoting Rhegmatogenous retinal detachment healing.

Rhegmatogenous retinal detachment (RRD) is a serious ocular emergency with a significant risk of blindness. A critical treatment objective for RRD is the sealing of retinal breaks. Retinal sealants offer a promising alternative to conventional surgery by effectively closing these breaks and potentially reducing complications. However, current sealants, such as fibrin glue, cyanoacrylate, and polyethylene glycol derivatives, suffer from limitations including weak adhesion, intraocular toxicity, and difficulty with intraocular administration, preventing their widespread use. This article reports on an injectable hydrogel (CMCS/4-arm-PEG-CHO, termed MPGel) for sealing retinal breaks in RRD. MPGel is formed through a Schiff base reaction between carboxymethyl chitosan (CMCS) and 4-arm poly(ethylene glycol) aldehyde (4-arm-PEG-CHO), enabling administration via a clinical 30G syringe. The aldehyde groups in MPGel form stable chemical bonds with tissue amino groups, ensuring robust adhesion. Ex vivo studies using a porcine retinal hole-closure assay and in vivo evaluation in a rabbit RRD model demonstrated that MPGel can be easily injected into retinal breaks and effectively seals large defects (approximately 2-3 disc diameters). These results indicate MPGel's strong capacity to promote RRD repair and its significant potential for clinical translation.