ACS Nano. 2025 Dec 16;19(49):41803-41815. doi: 10.1021/acsnano.5c15619. Epub 2025 Dec 4.

Engineering of Metal-Organic Networks as Band-Aid for the Repair of Osteoporotic Bone Fractures

Abstract
The treatment of osteoporotic bone fractures remains a critical challenge due to the dysregulated bone remodeling microenvironment characterized by excessive osteoclastic resorption, impaired osteogenic differentiation, angiogenic dysfunction, and chronic inflammation. In this work, we engineered a metal-organic network as a bone repair "band-aid" by integrating poly(ethylene glycol)-alendronate (PEG-ALN) conjugates with bioactive epigallocatechin gallate (EGCG), zinc, and calcium ions into a multifunctional scaffold. This design leverages the synergistic effects of anti-inflammatory and antioxidant properties of EGCG with the balancing osteogenic and osteoclastic functions of ALN, zinc, and calcium ions. In vitro studies demonstrated that the band-aid significantly enhanced the proliferation and differentiation of osteoblasts while promoting endothelial cell migration and tubule formation, indicating the robust osteogenic and angiogenic potential. In vivo evaluations in an osteoporotic bone fracture model revealed accelerated bone regeneration and improved microvascularization while maintaining a balanced immune response to prevent chronic inflammation. Mechanistically, the band-aid modulated macrophage polarization toward a pro-regenerative M2 phenotype and suppressed excessive osteoclast activity, thereby restoring the osteogenic-osteoclastic equilibrium. This study not only provides a therapeutic implant for osteoporotic bone repair but also proposes a strategy for designing immunomodulatory scaffolds that target the pathological bone microenvironment.

Keywords: bone repair; metal−organic networks; osteoporosis; polyphenols; tissue engineering.

Product: 8-arm-PEG-NHS