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. <i>In vitro</i> 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. <i>In vivo</i> 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.