Hollow Hydroxyapatite Microspheres Loaded with rhCXCL13 to Recruit BMSC for Osteogenesis and Synergetic Angiogenesis to Promote Bone Regeneration in Bone Defects

Jianhua Zeng,1,2,* Shilang Xiong,3,* Jingyu Zhou,4 Peng Wei,4 Kai Guo,1 Feng Wang,1 Min Ouyang,4 Zhisheng Long,5 Aihua Yao,6 Jingtang Li,7 Long Xiong,4 Desheng Wu1 1Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China; 2Department of Spine Surgery, People’s Hospital of Ganxian District, Ganzhou, Jiangxi, 341100, China; 3Department of Orthopedics, the First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, Jiangxi, 330006, China; 4Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China; 5Department of Spine Surgery, Jiangxi Provincial People’s Hospital the First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, China; 6School of Materials Science and Engineering, Tongji University, Shanghai, 201804, China; 7Department of Traumatology, Jiangxi provincial People’s Hospital the First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, China*These authors contributed equally to this workCorrespondence: Desheng Wu; Long Xiong, Email 1300116@tongji.edu.cn; ncxionglong2@126.comIntroduction: Bone tissue engineering is a promising method to treat bone defects. However, the current methods of preparing composite materials that mimic the complex structure and biological activity of natural bone are challenging for recruitment of bone marrow mesenchymal stem cells (BMSCs), which affects the application of these materials in situ bone regeneration. Hollow hydroxyapatite microspheres (HHMs) possess a natural porous bone structure, good adsorption, and slow release of chemokines, but have low ability to recruit BMSCs and induce osteogenesis. In this study, The HHM/chitosan (CS) and recombinant human C-X-C motif chemokine ligand 13 (rhCXCL13)-HHM/CS biomimetic scaffolds that optimize bone regeneration an