Tannic Acid–Collagen-Coated Calcium Carbonate Nanoparticles for Enhanced Calcium Uptake and Osteoporosis Treatment

Osteoporosis requires long-term management, yet current pharmacological therapies are limited by safety concerns. Calcium carbonate is a biocompatible and widely used calcium supplement; however, its low absorption efficiency restricts therapeutic effectiveness. Herein, a biomimetic calcium delivery system was constructed by depositing an ultrathin (~10 nm) tannic acid/fish collagen (TA/FC) nanolayer onto CaCO3 nanoparticles via coordination- and hydrogen bonding-mediated self-assembly. The TA/FC nanocoating modulates cellular internalization by activating multiple endocytic pathways, thereby enhancing nanoparticle uptake and intracellular calcium delivery. As a result, cellular calcium uptake increased by 5.6-fold, and the apparent absorption rate reached 93.2%, 4.9 times higher than that of medical-grade calcium carbonate. In vivo, CaCO3@TA/FC nanoparticles restored bone metabolic homeostasis, as indicated by increased serum calcium, decreased phosphate and alkaline phosphatase levels, and elevated osteoprotegerin expression. This was accompanied by significant improvements in bone microarchitecture, including increased bone mineral density, bone volume fraction, trabecular number and thickness, as well as recovery of mechanical strength. Overall, this work demonstrates that interfacial engineering enhances calcium bioavailability and improves the therapeutic performance of calcium carbonate.