Angiogenesis and osteogenesis enhanced by bFGF ex vivo gene therapy for bone tissue engineering in reconstruction of calvarial defects.
Reconstruction of bone defects by tissue engineered substitutes requires coordinated coupling between osteogenesis and angiogenesis. Basic fibroblast growth factor (bFGF or FGF-2) is a protein which acts actively in osteogenesis and angiogenesis during skeletal healing and development. It is hypothesized that BMSCs transfected with bFGF can directly stimulate regeneration of vascular tissue, and subsequently enhance osseous formation and remodeling after implantation of the tissue engineered bone. This study was designed to examine the impact of bFGF-BMSCs, seeded on nano-hydroxyapatite/polyamide66 (n-HA/PA66) composite scaffold, to enhance angiogenesis and osteogenesis in a calvarial critical-sized defect model in rats. To investigate the vascularization and bone formation of tissue engineered bone, the substrate was removed and processed for immunohistochemical, scanning electron microscopic examinations (SEM), reverse transcriptase-polymerase chain reaction (RT-PCR), dual energy X-ray absorptiometry (DEXA), microvessels counting, and new bone volume assay. The results demonstrate that bFGF mediated ex vivo gene transfer based on BMSCs can accelerate vascularization and bone regeneration on these composite scaffolds. The n-HA/PA66 scaffold combined with the bFGF-BMSCs may mimic the natural process of osteogenesis during repair of defect by tissue engineered bone.
State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu 610041, China.
Dan
D
Qu
Jihua
J
Li
Yubao
Y
Li
Ying
Y
Gao
Yi
Y
Zuo
Yuchun
Y
Hsu
Jing
J
Hu
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology; D017886:Durapatite / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000627:therapeutic use*; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020007:Implants, Experimental; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014161:Transduction, Genetic
C485184:enhanced green fluorescent protein; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; D017886:Durapatite