International Journal of Nanomedicine (Aug 2021)
Ursolic Acid Loaded-Mesoporous Hydroxylapatite/ Chitosan Therapeutic Scaffolds Regulate Bone Regeneration Ability by Promoting the M2-Type Polarization of Macrophages
Abstract
Xijiao Yu,1,2,* Yuxuan Wang,3,* Xiaoliang Liu,3 Yuwei Ge,3,4 Shanyong Zhang1 1Department of Oral Surgery, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, People’s Republic of China; 2Central Laboratory, Department of Endodontics, Jinan Stomatological Hospital, Jinan, Shandong, People’s Republic of China; 3Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuwei Ge; Shanyong Zhang Email [email protected]; [email protected]: 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, immunofluorescence, 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 candidates to cure the bone disease.Keywords: mesoporous hydroxylapatite, polarization, bone regeneration, ursolic acid, drug delivery
