Nanoparticle hydrogel system delivery of miR-494-3p to improve tendon healing by targeting CXXC4

Due to the poor healing capacity of tendons, the healing process is slow, with a risk of re-rupture post-injury. In this study, we found that miR-494-3p was one of the miRNAs with significant expression differences after tendon injury by sequencing in the rat Achilles tendon injury model. Therefore, we hypothesized that regulating miR-494-3p expression in tendons could improve tendon healing. Considering the long healing process of the tendons and the short half-life of miRNA, we hope to achieve the best efficacy by delivering miR-494-3p using a sustained-release nanoparticle hydrogel system. In the results, with an increase in miR-494-3p, the tendon biomechanics were significantly improved after 2-week repair, and the content of collagen I (Col I) also increased. Through bioinformatics prediction, double luciferase, and immunohistochemistry experiments, we confirmed that miR-494-3p targeting CXXC finger protein 4 (CXXC4) promoted tendon healing. In conclusion, the miR-494-3p/nanoparticles hydrogel delivery system can protect and sustainedly transfer miR-494-3p into tenocytes, block the translation of CXXC4, increase the expression of Col I, and ultimately improve tendon healing. A nanoparticle hydrogel delivery system of miRNA was constructed and applied to injured tendons. Finally, we confirmed that the miR-494-3p/nanoparticles hydrogel delivery system can protect and sustainedly transfer miR-494-3p into tenocytes, block the translation of CXXC4, increase the expression of Col I, and ultimately improve tendon healing.