Artificial joint replacement is a widely recognized treatment for arthritis and other severe joint conditions. However, one of the primary causes of failure in joint replacements is the loosening of the prosthesis. After implantation, wear particles between the implant and the adjacent bone tissue are the principal contributors to this loosening. Recently, exosomes have garnered significant interest due to their low immunogenicity and effective membrane binding. They have shown potential in promoting bone regeneration via the paracrine pathway. This review examines the role and mechanisms of exosomes derived from mesenchymal stem cells (MSCs) in bone regeneration, their impact on the integration of various implants into surrounding bone tissue and current challenges and future directions for the clinical application of exosomes. The Translational Potential of this Article: Emerging evidence suggests that mesenchymal stem cell-derived exosomes may offer a promising therapeutic strategy for aseptic prosthesis loosening, potentially mediated through mechanisms such as modulation of inflammatory responses, suppression of osteoclastogenesis, enhancement of osteogenic differentiation and facilitation of bone regeneration. Preclinical studies further indicate that the therapeutic potential of these extracellular vesicles could be optimized through bioengineering strategies, including surface modification and cargo-loading techniques, warranting further investigation to advance their clinical translation.