Immunoregulatory Biomaterials for Bone Tissue Engineering: Mechanisms, Design Strategies and Translational Challenges

Bone tissue engineering has progressed from bioinert scaffolds to bioactive and immunoregulatory biomaterials that actively interact with the host immune system. Successful bone regeneration depends not only on osteogenesis but also on the regulation of the immune micro-environment, particularly macrophage polarisation and the balance between pro- and anti-inflammatory responses. This review summarises the interactions between biomaterials and the immune system during bone healing, including host response mechanisms such as protein adsorption, foreign body reaction, and immune cell activation. Key biomaterial properties, such as surface chemistry, topography, mechanical characteristics, and composition, are discussed in relation to their immunomodulatory effects. In addition, current design strategies, including surface modification, ion release, and controlled delivery of bioactive factors, are highlighted. Finally, emerging evaluation approaches and current challenges in clinical translation are briefly discussed, with an outlook towards the development of adaptive biomaterials capable of improving bone regeneration outcomes.