Systematic Review to Identify Potential Extracellular Vesicle-Derived microRNAs for Arthrofibrosis Treatment

Arthrofibrosis is defined as the excessive accumulation of connective tissue in and around joints, which interferes with the range of motion required for activities of daily living. Although joint stiffness can be restored by surgical interventions such as adhesion lysis, arthroscopic debridement, and capsular release, arthrofibrosis tends to redevelop in the months following the surgery. Thus, there is a critical and urgent need to develop a non-invasive pharmacological-based therapy to prevent or resolve arthrofibrosis. A subclass of small extracellular vesicles called exosomes convey bioactive regulators like micro ribonucleic acids (miRNAs/miRs), which can function as both anti- and pro-fibrotic agents. Currently, there is no research of miRNA-based therapeutic potentials for treating arthrofibrosis. Previous research and clinical observations on fibrosis across organ systems suggests that there are commonalities in pathogenic mechanisms that can be targeted arthrofibrosis therapy. In this study, we collated and critically analyzed the existing literature of exosomal miRNAs in organ fibrosis to discover potential candidates for diagnosing, preventing and/or treating arthrofibrosis. Fifty-six articles were finally selected and categorized by anti- and pro-fibrotic candidates of miRNAs. Notably, let-7, miR-26, miR-29, miR-146, miR-148/-152, miR-214, miR-223, and miR-21 emerged as prominent candidates that should be investigated further for effectiveness in arthrofibrosis therapy.