Ursolic acid loaded-mesoporous hydroxylapatite/ chitosan therapeutic scaffolds regulate bone regeneration ability by promoting the m2-type polarization of macrophages

Abstract

Purpose: Mesoporous hydroxylapatite (MHAP) might be important for bone regeneration, and ursolic acid (UA) has anti-inflammatory effects. Accordingly, we developed, for the first time, ursolic acid-loaded MHAP-chitosan (MHAP-CS-UA) scaffolds to treat bone defects. Methods: In vitro, we synthesize biomaterial scaffolds. By SEM, XRD, EDS and FTIR, we test the performance of the hybrid scaffolds. By drug release, flow cytometry, immunofluor-escence, alizarin red staining, and Western blotting, we test the anti-inflammatory and osteo-inductive properties of scaffolds. In vivo, we verify osseointegration ability and bone regeneration. Results: The MHAP is a rod-shaped structure with a length of 100~300nm and a diameter of 40~60nm. The critical structure gives the micro-scaffold a property of control release due to the pore sizes of 1.6~4.3 nm in hydroxyapatite and the hydrogen bonding between the scaffolds and UA drugs. The released UA drugs could notably inhibit the polarization of macrophages to pro-inflammatory macrophages (M1 type) and promote the expression of osteogenic-related genes (COL1, ALP and OPG) and osteogenic-related proteins (BMP-2, RUNX2 and COL1). Conclusion: The MHAP-CS-UA scaffolds have good anti-inflammatory, osseointegration, osteo-inductivity and bone regeneration. And they will be the novel and promising candi-dates to cure the bone disease.