AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.2379
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RESEARCH ARTICLE

Three-dimensional-printed scaffolds functionalized with stem cell recruitment and cell respiration regulation for diabetic bone defects

Ke Jiang1,2 ,  Caiping Yan1,2 ,  Pengrui Zhang3 ,  Yongfu Xiong4,5 ,  Weikang Zhao1 ,  Jiangtao He3 ,  Lu Chen3 ,  Hanfeng Yang3 ,  Dianming Jiang2* ,  Wei Huang1* ,  Yuling Li1*
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1 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Orthopedic Laboratory of Chongqing Medical University, Chongqing, China
2 Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
3 Department of Orthopedics, Laboratory of Biological Tissue Engineering and Digital Medicine, Nanomedicine Innovation Research and Development Transformation Institute, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
4 Department of Hepatobiliary Surgery, Academician (Expert) Workstation, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
5 Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, China
IJB, 2379 https://doi.org/10.36922/ijb.2379
Submitted: 6 December 2023 | Accepted: 6 February 2024 | Published: 14 March 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

High-glucose microenvironment in diabetic patients is a source of damage to the cellular mitochondrial respiratory chain (MRC), which results in the generation of reactive oxygen species (ROS) and leads to mitochondrial dysfunction, cellular senescence, and enhanced apoptosis, eventually causing weakened cellular migration and differentiation as well as physical dysfunction. In patients with diabetic bone defects, the high-glucose microenvironment induces intracellular mitochondrial dysfunction and diminished migration and differentiation of bone marrow mesenchymal stem cells (BMSCs), leading to impaired bone regeneration. In this study, polycaprolactone (PCL) porous scaffolds were prepared by three-dimensional (3D) printing. The EPLQLKM (E7) and SS31 peptides were modified onto the surface of PCL porous scaffolds by chemical bonding to construct a 3D-printed porous scaffold system (PCL@SS31@E7) capable of stem cell recruitment and regulation of cellular MRC to treat diabetic bone defects. In vitro cellular energy metabolism and molecular biology experiments demonstrated that the scaffold system could continuously release E7 and SS31 peptides to recruit BMSCs, improve MRC function, reduce proton leakage, protect mitochondria, and promote proliferation and osteogenic differentiation of BMSCs to regenerate bone tissue in a high-glucose environment. In vivo experiments confirmed that the PCL@SS31@E7 porous scaffold induced regeneration of normal bone tissue in the area of femoral condylar bone defects in diabetic rats. The 3D-printed porous scaffold constructed in this study is a novel biomaterial with the functions of stem cell recruitment and targeted regulation of MRC and provides a new direction for the treatment of various diseases related to diabetes and MRC dysfunction. 

Keywords
3D printing
Stem cell recruitment
Mitochondrial respiratory chain
Diabetic bone defects
Bone regeneration
Funding
This work is supported by the National Natural Science Foundation of China (82102578 and 82102571), Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province (2023ZYD0071), China Postdoctoral Science Foundation (2022M720603, 2022M710564, and 2023MD734156), National Natural Science Foundation of Sichuan (24NSFSC1274), Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0104 and CSTB2022NSCQ-MSX0089), Research Project of Health Commission of Sichuan Province (2023-1601), Research Project of Nanchong Science and Technology Bureau (22SXJCQN0004 and 22SXQT0308), and Research Project of the Affiliated Hospital of North Sichuan Medical College (2022JB008, 2023ZD002, and 2023-2ZD001).
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Conflict of interest
The authors declare no conflicts of interest.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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