Self-healing Hydrogel Embodied with Macrophage-regulation and Responsive-gene-silencing Properties for Synergistic Prevention of Peritendinous Adhesion.

Anti-adhesion barriers such as films and hydrogels used to wrap repaired tendons are important for preventing the formation of adhesion tissue after tendon surgery. However, sliding of the tendon can compress the adjacent hydrogel barrier and cause it to rupture, which may then lead to unexpected inflammation. Here, a self-healing and deformable hyaluronic acid (HA) hydrogel was constructed as a peritendinous anti-adhesion barrier. Matrix metalloproteinase-2 (MMP-2)-degradable gelatin-methacryloyl (GelMA) microspheres (MSs) encapsulated with Smad3-siRNA nanoparticles were entrapped within the HA hydrogel to inhibit fibroblast proliferation and prevent peritendinous adhesion. Silencing effect of Smad3-siRNA nanoparticles was around 75% towards targeted gene. The mean adhesion scores of composite barrier group were 1.67±0.51 and 2.17±0.75 by macroscopic and histological evaluation, respectively. Furthermore, GelMA MSs were responsively degraded by upregulation of MMP-2, achieving on-demand release of siRNA nanoparticles to inhibit the formation of adhesion tissue. The proposed self-healing hydrogel anti-adhesion barrier with MMP-2-responsive drug release behavior is highly effective for decreasing inflammation and inhibiting tendon adhesion. Therefore, this research provides a new strategy for the development of safe and effective anti-adhesion barriers. This article is protected by copyright. All rights reserved.