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

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.