Teriparatide(Chengdu Shengnuo)

Osteoporosis, a systemic skeletal disorder characterized by reduced bone density and increased fracture risk, poses a significant global health challenge. While teriparatide (TRP), a first-line anabolic peptide drug, demonstrates substantial therapeutic benefits in osteoporosis management, its clinical use is restricted by the necessity for daily subcutaneous administration, leading to suboptimal patient compliance. To overcome this limitation, we developed an orally deliverable TRP formulation using biocompatible metal-organic framework nanoparticles (MOF-808 NPs) co-loaded with TRP and functionalized with transferrin targeting ligands (M@P@T NPs). The rationally designed nanoporous architecture coupled with transferrin surface modification synergistically protects TRP from acidic and enzymatic degradation in harsh gastrointestinal environments, while realizing controlled release of TRP in the phosphate-rich bloodstream. Leveraging the overexpression of transferrin receptors (TfR) on intestinal epithelial cells, the nanosystem facilitates receptor-mediated transcellular transport, enabling efficient systemic delivery of TRP with high oral bioavailability. After the one-month oral administration of low-dose M@P@T (200 μg kg^-1·day^-1) to osteoporosis model mice, therapeutic outcomes comparable to those achieved with subcutaneous TRP injections were observed, including increased bone mineral density, improved trabecular structure, and significant alleviation of osteoporosis symptoms. These findings suggest that this MOF-based oral TRP strategy has great potential for simplifying and improving the treatment of osteoporosis.

Osteoporotic bone defects remain a major clinical challenge due to impaired osteogenesis, insufficient angiogenesis, excessive osteoclast activity, and increased susceptibility to infection. To address these issues, we developed an injectable phosphocreatine-grafted gelatin hydrogel (GGP) incorporating hierarchically structured Zn-Cu particles functionalized with a teriparatide (PTH)/strontium-zinc phosphate (SrZnP) hybrid coating. This multifunctional hydrogel was fabricated via enzymatic and ionic coordination crosslinking, yielding improved mechanical properties and sustained release of Zn²⁺, Sr²⁺, and PTH. In vitro evaluations demonstrated that the hydrogel enhanced BMSC proliferation, osteogenic differentiation, and mineralization, promoted HUVEC migration, tube formation, and angiogenic marker expression, and simultaneously inhibited osteoclastogenesis and bacterial growth. Transcriptomic analysis and inhibitor experiments revealed a dual paracrine mechanism mediating bone-vascular coupling: BMSC-derived HIF-1α-VEGF signaling facilitated angiogenesis, while HUVEC-derived PI3K-Akt-BMP-2 signaling enhanced osteogenesis. In vivo, the PTH/SrZnP@ZnCu-GGP hydrogel significantly accelerated bone regeneration and neovascularization in an ovariectomized rat calvarial defect model, accompanied by upregulated expression of BMP-2, RUNX2, p-Akt, and CD31. Collectively, this injectable hydrogel system offers a robust and translationally feasible strategy for coordinated osteogenesis-angiogenesis coupling, osteoclast suppression, and antibacterial defense, thus holding strong potential for the regeneration of osteoporotic bone defects.