Advances in 3D bioprinting of immunoregulatory biomaterials for bone regeneration.

Bone defects caused by trauma, infection, tumour resection, and degenerative diseases remain major clinical challenges because successful regeneration requires coordinated regulation of inflammation, vascularisation, osteogenesis, and bone remodeling. Advances in osteoimmunology have demonstrated that immune responses are integral to each stage of bone healing, shifting biomaterial design from passive biocompatibility towards active and temporally coordinated immunomodulation. Three dimensional bioprinting provides a versatile platform for integrating material, structural, cellular, and biochemical cues within spatially defined constructs, thereby offering new opportunities to regulate the osteoimmune microenvironment. In this review, we first summarise the immune processes and key immune cell populations involved in the inflammatory, proliferative, and remodeling stages of bone repair, and discuss the major bioprinting technologies and bioink design principles relevant to immunoregulatory bone regeneration. We then examine how material composition, structural and surface cues, and biologically active components, including stem cells, cytokines, exosomes, and decellularised extracellular matrix, regulate immune cell states and their interactions with vascular and osteogenic processes. Particular emphasis is placed on moving beyond static macrophage polarisation towards multicellular, stage specific, and spatiotemporally controlled immunoregulation. Finally, current challenges and future directions are discussed, including responsive and multifunctional bioinks, controlled degradation and delivery, mechanistic evaluation, manufacturing standardisation, and clinical translation. Collectively, immunoregulatory bioprinting provides a promising framework for developing bone regenerative constructs that more closely coordinate with the dynamic biology of tissue repair.