Exosomes as Precise Regulators of the Osteoimmune Microenvironment: Engineering Strategies for Bone Regeneration

Bone homeostasis is a dynamically orchestrated process that is intricately regulated by the immune system. The emerging field of osteoimmunology has demonstrated that bone homeostasis and repair are governed by a sophisticated crosstalk between immune and skeletal cells, in which immune signals play a critical role in modulating osteogenesis and osteoclastogenesis. Nevertheless, conventional bone repair strategies frequently overlook immune modulation, instead prioritizing structural support or direct osteoinductive effects. Exosomes-endogenous nanovesicles characterized by low immunogenicity and high bioavailability-have emerged as potent mediators within the immune-bone axis. These vesicles mediate intercellular communication by delivering functional cargo, including miRNAs, proteins, and lipids, across biological barriers, thereby enabling precise regulation of inflammatory responses and immune cell polarization. Importantly, exosomes can reprogram the local immune microenvironment from a pro-inflammatory to a regenerative, anti-inflammatory state, thus promoting enhanced bone healing in complex clinical conditions such as osteoporosis and bone defects. This review systematically examines the molecular mechanisms through which exosomes modulate immune responses in bone biology, highlights their pivotal role in reshaping the osteoimmune microenvironment, and discusses their transformative potential in the development of next-generation, precision-based therapeutic approaches for bone regeneration.