Building Osteogenic Microenvironments with a Double-Network Composite Hydrogel for Bone Repair

Jiaying Li; Jinjin Ma; Qian Feng; En Xie; Qingchen Meng; Wenmiao Shu; Junxi Wu; Liming Bian; Fengxuan Han; Bin Li

doi:10.34133/research.0021

Building Osteogenic Microenvironments with a Double-Network Composite Hydrogel for Bone Repair

Research (Wash D C). 2023:6:0021. doi: 10.34133/research.0021. Epub 2023 Jan 10.

Authors

Jiaying Li¹, Jinjin Ma², Qian Feng³, En Xie², Qingchen Meng², Wenmiao Shu⁴, Junxi Wu⁴, Liming Bian^{5

6

7

8}, Fengxuan Han², Bin Li^{1

2}

Affiliations

¹ State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215006, China.
² Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
³ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
⁴ Department of Biomedical Engineering, University of Strathclyde, Glasgow G1 1QE, UK.
⁵ School of Biomedical Sciences and Engineering,South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China.
⁶ National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China.
⁷ Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, China.
⁸ Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, China.

Abstract

The critical factor determining the in vivo effect of bone repair materials is the microenvironment, which greatly depends on their abilities to promote vascularization and bone formation. However, implant materials are far from ideal candidates for guiding bone regeneration due to their deficient angiogenic and osteogenic microenvironments. Herein, a double-network composite hydrogel combining vascular endothelial growth factor (VEGF)-mimetic peptide with hydroxyapatite (HA) precursor was developed to build an osteogenic microenvironment for bone repair. The hydrogel was prepared by mixing acrylated β-cyclodextrins and octacalcium phosphate (OCP), an HA precursor, with gelatin solution, followed by ultraviolet photo-crosslinking. To improve the angiogenic potential of the hydrogel, QK, a VEGF-mimicking peptide, was loaded in acrylated β-cyclodextrins. The QK-loaded hydrogel promoted tube formation of human umbilical vein endothelial cells and upregulated the expression of angiogenesis-related genes, such as Flt1, Kdr, and VEGF, in bone marrow mesenchymal stem cells. Moreover, QK could recruit bone marrow mesenchymal stem cells. Furthermore, OCP in the composite hydrogel could be transformed into HA and release calcium ions facilitating bone regeneration. The double-network composite hydrogel integrated QK and OCP showed obvious osteoinductive activity. The results of animal experiments showed that the composite hydrogel enhanced bone regeneration in skull defects of rats, due to perfect synergistic effects of QK and OCP on vascularized bone regeneration. In summary, improving the angiogenic and osteogenic microenvironments by our double-network composite hydrogel shows promising prospects for bone repair.