Mechanism of Action Behind the Pain-Relief Effects of Extracellular Vesicles in Microfragmented Adipose Tissue: An In vitro and In vivo Study

Background Trapeziometacarpal (TMC) osteoarthritis is a prevalent and debilitating condition that impairs hand functionality and reduces quality of life. Current treatments—including conservative measures such as splinting and anti-inflammatory medications, as well as surgical interventions—often exhibit limited efficacy or involve invasive procedures. Novel therapeutic approaches are necessary to address the pain and functional limitations experienced by affected patients. Methods This study investigates the potential of extracellular vesicles (EVs) derived from microfragmented adipose tissue (aMAT) as a minimally invasive treatment for TMC osteoarthritis. EVs were characterized using morphological, proteomic, and functional analyses, revealing their ability to modulate cellular processes through proteins associated with extracellular matrix organization, wound healing, and inflammation regulation. Results Functional studies demonstrated that EVs modulate calcium signaling and mitochondrial activity, enhancing cellular bioenergetics and mitigating inflammation-induced dysfunction. Trial registration This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and adhered to all relevant national and institutional ethical guidelines for research involving human participants. Approval for the study was obtained from the Ethics Committee of Marche Region, protocol n. 154/2021. All participants provided written informed consent before enrollment in the study. They were informed about the study’s purpose, procedures, potential risks, and their right to withdraw at any time without consequences. Informed Patient Consent Statement: Informed consent was obtained from all individual participants included in the study, following the guidelines of the Human Research Approval Committee protocol number 2/2019.