A sustained-release Trametinib bio-multifunction hydrogel inhibits orthodontically induced inflammatory root resorption

Abstract

Orthodontic tooth movement (OTM) is a bone reconstruction process. In most cases, OTM could induce root resorption as a common side effect, called orthodontically induced inflammatory root resorption (OIIRR). OIIRR affects tooth health and interferes with the stability of orthodontic treatment. Osteoclasts, which perform bone resorption in OTM, attack cementum, causing OIIRR. Many signaling pathways are involved in the maturation and differentiation of osteoclasts, among which the ERK1/2 is one of the important pathways. In this experiment, we added Trametinib (Tra), a specific inhibitor of ERK1/2, to catechol-modified chitosan (CHI-C) and oxidized dextran (ODex) to form a CCOD–Trametinib composite hydrogel (CCOD–Tra) to prevent OIIRR. CCOD–Tra exhibited good biocompatibility, injectability, strong adhesion, good hemostatic function and sustained release of Tra. We performed local injection of CCOD–Tra into the periodontal tissues of rats. CCOD–Tra firmly adhered to the periodontal tissues and then released Tra to establish a good biological environment and maintain a drug concentration at a high level around the roots for a long time. H&E, TRAP, immunochemistry staining and micro-CT indicated that CCOD–Tra had a good effect in terms of preventing OIIRR. Cell experiments showed that CCOD–Tra reduced the expression of TRAP, MMP-9 and C-FOS in osteoclast cells through the ERK1/2 signaling pathway to inhibit the differentiation and maturation of osteoclasts. Based on the above results, we concluded that CCOD–Tra had the ability to prevent OIIRR, the high adhesion and injectability of CCOD may provide better therapeutic ideas for clinical prevention of OIIRR.