The treatment efficacy of bone tissue engineering strategy for repairing segmental bone defects under diabetic condition

Xiangsheng Wang; Can Xiang; Chunhua Huang; Hanxiao Cheng; Zhentao Zhou; Jufang Zhang; Hui Xie

doi:10.3389/fbioe.2024.1379679

The treatment efficacy of bone tissue engineering strategy for repairing segmental bone defects under diabetic condition

Front Bioeng Biotechnol. 2024 Apr 26:12:1379679. doi: 10.3389/fbioe.2024.1379679. eCollection 2024.

Authors

Xiangsheng Wang^#^{1

2}, Can Xiang^#³, Chunhua Huang^#¹, Hanxiao Cheng², Zhentao Zhou², Jufang Zhang², Hui Xie⁴

Affiliations

¹ Department of Plastic Surgery, Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Hubei, China.
² Department of Plastic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
³ Department of Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
⁴ Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

^# Contributed equally.

Abstract

Background: Diabetes mellitus is a systematic disease which exert detrimental effect on bone tissue. The repair and reconstruction of bone defects in diabetic patients still remain a major clinical challenge. This study aims to investigate the potential of bone tissue engineering approach to improve bone regeneration under diabetic condition.

Methods: In the present study, decalcified bone matrix (DBM) scaffolds were seeded with allogenic fetal bone marrow-derived mesenchymal stem cells (BMSCs) and cultured in osteogenic induction medium to fabricate BMSC/DBM constructs. Then the BMSC/DBM constructs were implanted in both subcutaneous pouches and large femoral bone defects in diabetic (BMSC/DBM in DM group) and non-diabetic rats (BMSC/DBM in non-DM group), cell-free DBM scaffolds were implanted in diabetic rats to serve as the control group (DBM in DM group). X-ray, micro-CT and histological analyses were carried out to evaluate the bone regenerative potential of BMSC/DBM constructs under diabetic condition.

Results: In the rat subcutaneous implantation model, quantitative micro-CT analysis demonstrated that BMSC/DBM in DM group showed impaired bone regeneration activity compared with the BMSC/DBM in non-DM group (bone volume: 46 ± 4.4 mm³ vs 58.9 ± 7.15 mm³, *p < 0.05). In the rat femoral defect model, X-ray examination demonstrated that bone union was delayed in BMSC/DBM in DM group compared with BMSC/DBM in non-DM group. However, quantitative micro-CT analysis showed that after 6 months of implantation, there was no significant difference in bone volume and bone density between the BMSC/DBM in DM group (199 ± 63 mm³ and 593 ± 65 mg HA/ccm) and the BMSC/DBM in non-DM group (211 ± 39 mm³ and 608 ± 53 mg HA/ccm). Our data suggested that BMSC/DBM constructs could repair large bone defects in diabetic rats, but with delayed healing process compared with non-diabetic rats.

Conclusion: Our study suggest that biomaterial sacffolds seeded with allogenic fetal BMSCs represent a promising strategy to induce and improve bone regeneration under diabetic condition.

Keywords: bone regeneration; bone tissue engineering; decalcified bone matrix; diabetes mellitus; mesenchymal stem cells.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (Grant No. 82002060) and the Foundation of Union Jingshan Hospital (2023-XHJS-004, 2023-XHJS-015).