title: Acceleration of bone-defect repair by using A-W MGC loaded with BMP2 and triple point-mutant HIF1α-expressing BMSCs.
abstract: BACKGROUND
  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 HIF1α(mu) (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 HIF1α(mu) 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).
  
  
  CONCLUSIONS
  Engineered A-W MGC with BMP2 and HIF1α(mu)-expressing BMSCs exhibits comparable therapeutic effects of bone-defect repair as an autologous bone graft.
authors.affiliation: Department of Orthopedics, The Affiliated First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, 110001, Shenyang, Liaoning province, China. 469185958@qq.com.|2nd Ward of Bone and Joint, The First Affiliated Hospital of Liaoning Medical University, No.2, Wuduan, Renmin Street, 121001, Jinzhou, China. 469185958@qq.com.
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Biobank, The First Affiliated Hospital of Liaoning Medical University, No.2, Wuduan, Renmin Street, 121001, Jinzhou, China. lichenxuna@126.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: 2nd Ward of Bone and Joint, The First Affiliated Hospital of Liaoning Medical University, No.2, Wuduan, Renmin Street, 121001, Jinzhou, China. wanghao2014jz@126.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The Affiliated First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, 110001, Shenyang, Liaoning province, China. guangyufancmd@sina.com.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Fan
mesh_terms: D000818:Animals; D001031:Apatites / Q000627:therapeutic use*; D015153:Blotting, Western; D016026:Bone Marrow Transplantation / Q000379:methods*; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects*; D002516:Ceramics / Q000627:therapeutic use*; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000502:physiology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D017354:Point Mutation; D011817:Rabbits; D011884:Radius / Q000293:injuries*; D012824:Silicic Acid / Q000627:therapeutic use*; D054457:Tissue Scaffolds
chemical_list: D001031:Apatites; D055396:Bone Morphogenetic Protein 2; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C077777:apatite-wollastonite-containing glass ceramic; D012824:Silicic Acid