Delivery of PDGF-B and BMP-7 by mesoporous bioglass/silk fibrin scaffolds for the repair of osteoporotic defects

被引:210
作者
Zhang, Yufeng [1 ]
Cheng, Ning
Miron, Richard
Shi, Bin
Cheng, Xiangrong
机构
[1] Wuhan Univ, State Key Lab Breeding Base Basic Sci Stomatol Hu, Sch & Hosp Stomatol, Wuhan 430079, Peoples R China
关键词
Gene therapy; Osteoporosis; Scaffold; PDGF; BMP; Adenovirus; BONE MORPHOGENETIC PROTEIN-2; MESENCHYMAL STEM-CELLS; MARROW STROMAL CELLS; GROWTH-FACTOR; GENE-THERAPY; ADENOVIRAL TRANSFER; EXHIBITS SAFETY; CLINICAL-USE; FRACTURES; RATS;
D O I
10.1016/j.biomaterials.2012.06.021
中图分类号
R318 [生物医学工程];
学科分类号
100103 [病原生物学];
摘要
Osteoporosis is a chronic disease affecting millions of people worldwide caused by an imbalance between bone-forming osteoblasts and bone-resorbing osteoclasts. Despite recent developments in pharmacological agents to prevent osteoporotic-related fractures, much less attention has been placed on the repair of bone defects following fracture. Critical to this process is the recruitment of mesenchymal stem cells (MSCs) to defect sites by growth factors. One method which has been effective for the sustained release of growth factors is that of gene therapy. The aim of the present study was to investigate newly developed mesoporous bioglass/silk fibrin scaffolds containing adPDGF-b and adBMP-7 into osteoporotic critical-sized femur defects in ovariectomised rats following treatment periods of 2 and 4 weeks. In vivo osteogenetic efficiency evaluated by mu-CT analysis, hematoxylin and eosin staining, and immunohistochemical (type I collagen, osteopontin and BSP) revealed significantly new bone formation in defects containing adenovirus for both PDGF-b and BMP-7 when compared to scaffolds alone and scaffolds containing BMP-7. TRAP-positive staining also demonstrated the ability for these scaffolds to be degraded over time and initiate bone turnover/remodeling. Although the use of gene therapy for clinical applications is still in its infancy, results from the present study demonstrate their potent ability to recruit mesenchymal progenitor cells through sustained release of PDGF-b and BMP-7 which may be beneficial for patients suffering from osteoporotic-related fractures. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:6698 / 6708
页数:11
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