Use of a pH-responsive imatinib mesylate sustained-release hydrogel for the treatment of tendon adhesion by inhibiting PDGFRβ/CLDN1 pathway

Abstract

Adhesion after tendon injury, which can result in limb movement disorders, is a common clinical complication; however, effective treatment methods are lacking. Hyaluronic acid hydrogels are a new biomedical material used to prevent tendon adhesion owing to their good biocompatibility. In addition, potential drugs that inhibit adhesion formation have gradually been discovered. The anti-adhesion effects of a combination of loaded drugs into hydrogels have become an emerging trend. However, current drug delivery systems usually lack specific regulation of drug release, and the effectiveness of drugs for treating tendon adhesions is mostly flawed. In this study, we identified a new drug, imatinib mesylate (IM), that prevents tendon adhesion and explored its related molecular pathways. In addition, we designed a pH-responsive sustained-release hydrogel for delivery. Using the metal-organic framework ZIF-8 as a drug carrier, we achieved controlled drug release to increase the effective drug dose at the peak of adhesion formation to achieve better therapeutic effects. The results showed that IM blocked the formation of peritendon adhesions by inhibiting the PDGFRβ/ERK/STAT3/CLDN1 pathway. Furthermore, the hydrogel with ZIF-8 exhibited better physical properties and drug release curves than the hydrogel loaded only with drugs, showing better prevention and treatment effects on tendon adhesion.

Keywords

• Hydrogel
• ZIF-8
• Peritendinous adhesion
• Imatinib mesylate
• Claudin 1