Functionalized blended 3D-printed artificial bone with adjustable homeostasis for osteoporotic alveolar defect repair

Repair of osteoporotic alveolar bone defect remains challenging owing to a local microenvironment characterized by impaired osteogenesis and heightened osteoclast activity, which constrains new bone formation. Conventional bone repair materials are ill-equipped to specifically target and modulate this complex milieu, highlighting the urgent need for biomaterials that integrate structural support with microenvironment-responsive, dual regulation of bone remodeling. Here, leveraging the putative coordination interaction between nano-hydroxyapatite (Ca²⁺ sites) and zoledronic acid (ZOL) (phosphonate groups), we endowed a 3D-printed poly(lactic-co-glycolic acid) artificial bone with high drug-loading capacity and sustained, localized delivery-associated with matrix biodegradation and gradual desorption/dissociation of putatively bound ZOL and thereby enhance regeneration of osteoporotic defects. Our results demonstrate that an appropriately dosed ZOL-co-blended printed artificial bone significantly suppresses osteoclast activation-related bone metabolic indices while concomitantly promoting the expression of osteogenic differentiation markers, indicative of bidirectional regulation of bone homeostasis. In an osteoporotic rat distal femoral condyle defect model, the ZOL-blended scaffold markedly improved the volume and quality of newly formed bone under pathological conditions, recalibrated peri-implant bone metabolism, and strengthened implant interfacial bone regeneration. This integrative strategy-uniting 3D-printed architecture, mineral-mimetic chemistry, and localized antiresorptive therapy-offers a clinically promising and potentially translatable solution for the regenerative treatment of osteoporotic alveolar bone defect. • 3D-printed PLGA/nHA with mineral-mimetic ZOL chelation. • Sustained local release enables bidirectional remodeling control. • Clinically translatable therapy for osteoporotic alveolar bone defects.