Biofunctionalized composite scaffold to potentiate osteoconduction, angiogenesis, and favorable metabolic microenvironment for osteonecrosis therapy

Tongtong Zhu; Mengyang Jiang; Mingran Zhang; Liguo Cui; Xiaoyu Yang; Xukai Wang; Guangyao Liu; Jianxun Ding; Xuesi Chen

doi:10.1016/j.bioactmat.2021.08.005

Biofunctionalized composite scaffold to potentiate osteoconduction, angiogenesis, and favorable metabolic microenvironment for osteonecrosis therapy

Bioact Mater. 2021 Aug 20:9:446-460. doi: 10.1016/j.bioactmat.2021.08.005. eCollection 2022 Mar.

Authors

Tongtong Zhu¹, Mengyang Jiang², Mingran Zhang^{1

3}, Liguo Cui³, Xiaoyu Yang³, Xukai Wang¹, Guangyao Liu¹, Jianxun Ding³, Xuesi Chen³

Affiliations

¹ Department of Orthopedics, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun, 130033, PR China.
² Department of Ophthalmology, The Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, 130041, PR China.
³ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, PR China.

Abstract

Osteonecrosis is a common orthopedic disease in clinic, resulting in joint collapse if no appropriate treatment is performed in time. Core decompression is a general treatment modality for early osteonecrosis. However, effective bone regeneration in the necrotic area is still a significant challenge. This study developed a biofunctionalized composite scaffold (PLGA/nHA₃₀ ^VEGF) for osteonecrosis therapy through potentiation of osteoconduction, angiogenesis, and a favorable metabolic microenvironment. The composite scaffold had a porosity of 87.7% and compressive strength of 8.9 MPa. PLGA/nHA₃₀ ^VEGF had an average pore size of 227.6 μm and a water contact angle of 56.5° with a sustained release profile of vascular endothelial growth factor (VEGF). After the implantation of PLGA/nHA₃₀ ^VEGF, various osteogenic and angiogenic biomarkers were upregulated by 2-9 fold compared with no treatment. Additionally, the metabolomic and lipidomic profiling studies demonstrated that PLGA/nHA₃₀ ^VEGF effectively regulated the multiple metabolites and more than 20 inordinate metabolic pathways in osteonecrosis. The excellent performances reveal that the biofunctionalized composite scaffold provides an advanced adjuvant therapy modality for osteonecrosis.

Keywords: Angiogenesis; Biofunctionalized scaffold; Favorable metabolic microenvironment; Osteoconduction; Osteonecrosis therapy.