Osteoclast-regulatory biomaterials: Direct cellular intervention and indirect microenvironment modulation

Osteoclasts are central effector cells in osteolytic diseases. Their differentiation and resorptive activity are regulated by stage-dependent cellular programs and by spatially and temporally changing pathological cues. Aberrant osteoclast activation is therefore shaped by both cell-intrinsic signaling networks and extrinsic microenvironmental drivers. Recent advances in osteoclast-regulatory biomaterials include strategies that directly regulate osteoclast-lineage cells or modulate osteoclast-supportive microenvironments. In this review, we first summarize the biological basis of osteoclast overactivation and current clinical interventions. We then organize biomaterial strategies into a pathology-oriented framework covering direct regulation of osteoclast commitment, maturation, resorptive function and survival, and indirect regulation through osteoimmune, stromal, physicochemical and organ-bone axis-related mechanisms. Building on these biomaterial strategies and the clinical challenges of osteoclast-targeted intervention, we propose self-adaptiveness as an important future direction for osteoclast-regulatory biomaterials. Moreover, we also discuss emerging evaluation platforms that may strengthen the mechanistic assessment of stage-matched regulation, spatial localization, and remodeling compatibility. By linking biomaterials design to osteoclast biology and therapeutic requirements, this review provides a basis for future development of osteoclast-regulatory biomaterials with improved pathological adaptiveness.