Icariin delivery system based on covalent organic framework materials: dual effects of immune modulation and osteogenesis promotion

Abstract

Bone defects, induced by trauma, infection, tumor resection, osteoporosis, and congenital deformities, severely affect patient health both physiologically and psychologically, imposing substantial burdens on healthcare systems and public resources. Bone defect repair involves a complex biological process that orchestrates events such as immune modulation and osteogenic differentiation. Consequently, ideal materials for bone defect regeneration should possess capabilities in both immune regulation and osteogenesis. In this study, we synthesized a kind of covalent organic framework (COF) nanoparticles at room temperature and modified their surface with polydopamine (PDA), resulting in PDA-functionalized COFs (PCOFs). Utilizing the adhesive properties of PDA, we successfully loaded icariin (ICA) onto the PCOFs nanoparticles, forming ICA@PCOFs. Comprehensive characterization techniques, including visual inspection, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA), confirmed the successful synthesis of ICA@PCOFs nanoparticles. Subsequent optimal concentration determination via the CCK-8 assay, and further experiments including alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and immunofluorescent staining for osteocalcin (OCN), runt-related transcription factor 2 (Runx2), inducible nitric oxide synthase (iNOS), and mannose receptor (CD206), assessed their capability to modulate macrophage polarization and promote osteogenesis. The results revealed that ICA-loaded nanoparticles demonstrated significant potential in vitro for immune regulation and promoting stem cell osteogenic differentiation. These findings suggest that ICA@PCOFs nanoparticles could represent a promising therapeutic platform for bone defect regeneration, offering dual functionalities in immune modulation and osteogenesis promotion.