Zn/Sr dual ions-collagen co-assembly hydroxyapatite enhances bone regeneration through procedural osteo-immunomodulation and osteogenesis

Zhenyu Zhong; Xiaodan Wu; Yifan Wang; Mengdie Li; Yan Li; XuLong Liu; Xin Zhang; Ziyang Lan; Jianglin Wang; Yingying Du; Shengmin Zhang

Bioactive Materials (Apr 2022)

Zn/Sr dual ions-collagen co-assembly hydroxyapatite enhances bone regeneration through procedural osteo-immunomodulation and osteogenesis

Zhenyu Zhong,
Xiaodan Wu,
Yifan Wang,
Mengdie Li,
Yan Li,
XuLong Liu,
Xin Zhang,
Ziyang Lan,
Jianglin Wang,
Yingying Du,
Shengmin Zhang

Affiliations

Zhenyu Zhong: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
Xiaodan Wu: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
Yifan Wang: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
Mengdie Li: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
Yan Li: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
XuLong Liu: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
Xin Zhang: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
Ziyang Lan: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA
Jianglin Wang: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China; Institute of Regulatory Science for Medical Devices, Huazhong University of Science and Technology, Wuhan, 430074, China
Yingying Du: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China; Institute of Regulatory Science for Medical Devices, Huazhong University of Science and Technology, Wuhan, 430074, China; Corresponding author. Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China.
Shengmin Zhang: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China; Institute of Regulatory Science for Medical Devices, Huazhong University of Science and Technology, Wuhan, 430074, China; Corresponding author. Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, 430074, China.

Journal volume & issue: Vol. 10
pp. 195 – 206

Abstract

Read online

The immune microenvironment induced by biomaterials played vital roles in bone regeneration. Hydroxyapatite (HA) and its ion-substituted derivates represent a large class of core inorganic materials for bone tissue engineering. Although ion substitution was proved to be a potent way to grant HA more biological functions, few studies focused on the immunomodulatory properties of ion-doped HA. Herein, to explore the potential osteoimmunomodulatory effects of ion-doped HA, zinc and strontium co-assembled into HA through a collagen template biomimetic way (ZnSr-Col-HA) was successfully achieved. It was found that ZnSr-Col-HA could induce a favorable osteo-immune microenvironment by stimulating macrophages. Furthermore, ZnSr-Col-HA demonstrated a procedural promoting effect on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. Specifically, the osteo-immune microenvironment acted as a dominant factor in promoting osteogenic gene expressions at the early stage through OSM signal pathway. Whereas the direct stimulating effects on BMSCs by Zn2+/Sr2+ were more effectively at the later stage with Nfatc1/Maf and Wnt signals activated. In vivo study confirmed strong promoting effects of ZnSr-Col-HA on critical-sized cranial defect repair. The current study indicated that such a combined biomaterial design philosophy of dual ion-doping and biomimetic molecular co-assembly to endow HA applicable osteoimmunomodulatory characteristics might bring up a new cutting-edge concept for bone regeneration study.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

About the journal

Abstract

Keywords