Mesenchymal Stem Cell-Derived Exosomes for Bone Regeneration: Modification Strategies and miRNA-Mediated Modulation of Osteogenic Signaling

Bone tissue regeneration remains a major clinical challenge, and exosomes secreted by mesenchymal stem cells (MSCs) have emerged as attractive cell-free therapeutic tools. To enhance their efficacy and local action, exosomes can be modified to enrich them with regulatory factors and impregnated into biocompatible matrices. This review summarizes recent advances in engineering MSC-derived exosomes for bone regeneration. Strategies analyzed include physicochemical modification of donor MSCs, direct exosome modification, and genetic modification of MSCs to enrich exosomes with therapeutic molecules such as bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor (VEGF), and regulatory miRNAs. In addition, the role of these miRNAs in osteogenic signaling was analyzed. Modified exosomes demonstrate enhanced osteogenic, angiogenic, and immunomodulatory effects in vitro and in vivo, particularly when combined with biomaterial scaffolds for sustained release. Thus, engineered MSC-derived exosomes constitute an effective approach for bone tissue engineering and show potential for clinical translation.