Tough and self-adhesive zwitterionic hydrogels with mechano-responsive release of bFGF for tympanic membrane repair

Abstract

The tympanic membrane (TM) is constantly in a state of vibrating. However, there is currently a lack of drug-delivery scaffolds suitable for the dynamic environment of TM perforation. In this study, a mechano-responsive tough hydrogel was developed. It consists of basic fibroblast growth factor (bFGF)-loaded sodium alginate (SA) microspheres, polysulfobetaine methacrylate (polySBMA), and gelatin methacrylate (GelMA). This hydrogel was designed to serve as a TM scaffold to promote perforation healing under dynamic conditions. bFGF was encapsulated in SA microspheres, which were then incorporated into polySBMA-GelMA hydrogels through photo-initiated free radical polymerization. The mechanical properties, tissue adhesiveness, swelling properties, and degradation of the hydrogels were evaluated before and after microsphere incorporation. It was observed that incorporating bFGF-loaded SA microspheres did not significantly impact the adhesion and degradation mechanisms of the hydrogel. The compressive strength and tensile strength of the microsphere-incorporated hydrogel were up to 6.6 MPa and 64.1 kPa, respectively, suitable for a TM scaffold. The release behavior of bFGF from the hydrogel could be controlled by vibration stimulation without significantly affecting the hydrogel's mechanical properties, indicating a mechano-responsive nature of the hydrogel. The in vitro cytotoxicity assay demonstrated that the hydrogels showed no cytotoxic effects. Moreover, cell culture assays demonstrated that vibration stimulation could enhance the release of bFGF, significantly promoting cell proliferation and migration. The results demonstrate the significant potential of the mechano-responsive hydrogel as a scaffold for repairing TM perforations.