Polylactic acid/polycaprolactone in combination with marrow mesenchymal stem cells modified by bone morphogenetic protein 2 for the repair of bone defect during vascularization
- VernacularTitle:聚乳酸/聚己内酯生物可降解人工骨复合骨形态发生蛋白2基因转染骨髓基质干细胞修复骨缺损的血管化过程
- Author:
Wei YU
;
Jianjun LI
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2008;12(19):3761-3764
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Revascularization is necessary for tissue-engineered bone implantation by osteogenesis to effectively repair bone defect.OBJECTIVE: To evaluate marrow mesenchymal stem cells (MSCs) modified by bone morphogenetic protein 2 (BMP-2) in combination with polylactic acid/polycaprolactone (PLA/PCL) to repair rabbit radial bone defect during the vascularization, and to investigate the promotive effects of BMP-2 gene on the vascularization of bone graft.DESIGN: Randomized controlled animal study.SETTING: This study was performed in the Central Laboratory of China Medical University from January to December 2005.MATERIALS: PLA/PCL with 150-250 μm pore diameter and 90% interval porosity was provided by Changchun Applied Chemistry Institute, Chinese Academy of Science. Sixty 3-month-old New Zealand rabbits were selected in this study.METHODS: Sixty rabbits were randomly divided into four groups with 15 rabbits in each group. Subsequently, middle segments of bilateral radial bone were obtained to establish 1.5-cm bone defect models that were implanted with processed artificial bones. Adenovirus carrying BMP-2 (AD-BMP-2) group: Artificial bones were processed with transfected BMP-2 cells plus PLA/PCL; Control group: Artificial bones were processed with adenovirus carrying β-gal gene (Ad-Lacz) plus PLA/PCL; Non-transfection group: Artificial bones were processed with non-transfected cells plus PLA/PCL; PLA/PCL group: PLA/PCL alone for transplantation.MAIN OUTCOME MEASURES: Four, eight, and twelve weeks after surgery, X-ray was used to observe new bone formation; stereoscopic microscope to observe distribution of microvessels; haematoxylin-eosin staining to detect the relationship between microvessels and bone formation; transmission electron microscope to investigate the correlation between osteoblasts and vascular endothelial cells, detect vascular endothelial growth factor expression, and calculate the number of microvessels.RESULTS: Four postoperative weeks in the AD-BMP-2 group, numerous microvessels were observed; stent pore was full of cartilage calluses; active osteoblasts grew around microvessels; vascular endothelial growth factor expression and numbers of microvessels were higher and more than those in other groups. Eight postoperative weeks, osteoblasts gradually increased in the bone graft; microvessels circuitously expanded and connected each other; cartilage callus changed into trabecular bone. Twelve postoperative weeks, cortical bones were successive; medullary cavity recanalized; microvessels longitudinally arranged in order. Ability of bone formation in the control group and non-transfection group was weak, and vascular regeneration was slow; 12 postoperative weeks, bone defect was primarily repaired; microvessels were distributed along the pores of newborn bone trabecula. Newborn vessels were hard found in the PLA/PCL group at each time point. Twelve postoperative weeks, bone extremities sclerotized, and defect regions were fully filled by fiber tissues.CONCLUSION: Transfected BMP-2 gone by up-regulating vascular endothelial growth factor expression can indirectly induce vascularization of bone graft, promote survival of seed cells, and accelerate bone formation.
