Abstract

BackgroundThe goal of this study is to explore the effects of A-W MGC (apatite-wollastonite magnetic bioactive glass-ceramic) loaded with BMP2 (bone morphogenetic protein 2)- and HIF1αmu (hypoxia-inducible factor 1 mutation)-expressing BMSCs (bone marrow mesenchymal stem cells) on the bone defect repair.Methods(1) BMSCs were infected with viral solution containing BMP2 and HIF1αmu with the best MOI (multiplicity of infection). The efficiency was observed via hrGFP (human renilla reniformis green fluorescent protein). (2) The cells were divided into five groups (A–E), and ALP (alkaline phosphatase) activity was measured. (3) BMP2 and HIF1α (hypoxia-inducible factor 1α) protein were measured. (4) A-W MGC was loaded with BMSCs that contain the genes and implanted into the bone defect model. The animals were sacrificed 8 and 12 weeks later. (5) The healing was measured with X-ray, histology, and biomechanics.Results(1) BMSCs in A–D showed high transfection efficiency. (2) ALP in A and B was higher than the others (p = 0.041 or 0.038); A was higher than B (p = 0.038); (3) BMP2 in A and B was higher than the others (p = 0.014). HIF1α in A and C was higher than the others (p = 0.020). (4) 8 and 12 weeks after, an X-ray indicated that bone defect was nearly fully repaired in A and C. (5) 12 weeks after, the bone remodeling was complete in A and C. (6) The flexural strength in A and C was stronger than the others (p = 0.043).ConclusionEngineered A-W MGC with BMP2 and HIF1αmu-expressing BMSCs exhibits comparable therapeutic effects of bone-defect repair as an autologous bone graft.

Highlights

  • The goal of this study is to explore the effects of A-W Apatite-wollastonite magnetic bioactive glass-ceramic (MGC) loaded with Bone morphogenetic protein 2 (BMP2)- and HIF1αmuexpressing Mesenchymal stem cells (BMSCs) on the bone defect repair

  • In this study, we used A-W MGC scaffold loaded with BMSCs that were infected with BMP2 and Hypoxia-inducible factor 1 mutation (HIF1αmu) genes for the treatment of in vivo bone defects and achieved therapeutic effects that were comparable with an autogenous bone graft

  • We found that the Alkaline phosphatase (ALP) activity significantly increased in the BMSCs that were infected either with HIF1αmu plus BMP2 or with only BMP2, compared with uninfected BMSCs

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Summary

Introduction

The goal of this study is to explore the effects of A-W MGC (apatite-wollastonite magnetic bioactive glass-ceramic) loaded with BMP2 (bone morphogenetic protein 2)- and HIF1αmu (hypoxia-inducible factor 1 mutation)expressing BMSCs (bone marrow mesenchymal stem cells) on the bone defect repair. (3) BMP2 and HIF1α (hypoxia-inducible factor 1α) protein were measured. The breakthrough in creating a new type of engineered bone grafts, which combine the osteogenic factors, osteogenic stem cells, and the artificial bone scaffold, provides a new way for the bone-defect treatment. BMP (bone morphogenetic protein) is one of the osteogenic factors that play important roles in the ontogenesis. The transfected osteogenic cells stop growing due to insufficient nutrient supply, resulting in the difficulty of new bone formation inside the engineered bone graft. It is critical to build an effective network of

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