Biomaterial-based strategies for osteoporosis treatment and bone regeneration: advances and translational challenges.

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass, deterioration of bone microarchitecture, and increased susceptibility to fragility fractures. Although conventional antiresorptive and anabolic drugs effectively reduce fracture risk in many patients, their clinical utility is restricted by poor tissue specificity, systemic adverse effects, adherence problems, discontinuation-related risks, and their limited capacity to regenerate osteoporotic bone defects after trauma or surgery. Biomaterial-based strategies provide complementary opportunities by combining local structural support, controlled therapeutic delivery, and microenvironmental regulation. In this review, we discuss biomaterial design from an osteoporosis-specific perspective, emphasizing how disease-associated abnormalities-impaired osteoblast function, excessive osteoclast activity, reduced angiogenesis, inflammatory dysregulation, compromised extracellular matrix quality, and weakened mechanical integrity-can be addressed by scaffolds, targeted drug delivery systems, and biologically derived platforms. Ceramic, polymeric, and composite scaffolds are compared with respect to osteoconduction, ion-mediated signaling, mechanical support, and manufacturability. Bone-targeted nanoparticles, injectable hydrogels, and stimuli-responsive carriers are evaluated as strategies for the localized delivery of antiresorptive agents, anabolic molecules, nucleic acids, and osteogenic cues. We further summarize platelet-rich plasma/platelet-rich fibrin, growth factor-loaded matrices, mesenchymal stem cell-laden scaffolds, extracellular vesicle-functionalized systems, and gene-activated matrices as emerging biological or cell-free regenerative platforms. Finally, key translational barriers, including long-term safety, reproducible manufacturing, standardized osteoporotic models, and regulatory pathways for combination products, are discussed. Overall, biomaterials should not be viewed as replacements for established pharmacotherapy but as disease-tailored local interventions that may improve osteoporotic fracture repair and bone regeneration when integrated with rational clinical management.