缓释血小板衍生生长因子BB的纳米珍珠层/聚乳酸/纤维蛋白胶复合支架修复兔桡骨缺损的实验研究
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摘要
目的评价缓释血小板衍生生长因子BB(PDGF-BB)的纳米珍珠层/聚乳酸/纤维蛋白胶复合支架对骨缺损的修复作用。方法取24只成年雄性新西兰大白兔建立双侧桡骨15 mm骨缺损模型,随机分为4组,每组6只;分别置入聚乳酸支架(A组),纳米珍珠层/聚乳酸支架(B组)和缓释PDGF-BB的纳米珍珠层/聚乳酸/纤维蛋白胶复合支架(C组),不置入支架材料的为空白对照组。术后4、8、12周取材,通过大体观察、X线检查、骨密度测定、Micro-CT扫描重建和病理组织学评价三组支架材料的成骨作用。结果术后大体观察发现空白对照组骨缺损未修复,骨缺损断端硬化,而其他3组骨缺损均有不同程度修复。各时间点Lane-Sandhu X线评分,C组均优于B组,有统计学差异(P<0.05);B组优于A组和空白对照组,有统计学差异(P<0.01);各时间点C组的骨密度显著高于A与B组,有统计学差异(P<0.05)。Micro-CT和病理组织学结果提示C组骨修复效果较A与B组更好。结论缓释PDGF-BB的纳米珍珠层/聚乳酸/纤维蛋白胶复合支架具有明显促进兔桡骨缺损修复的作用。
Objective To evaluate the effect of bone defect repair using the controlled release of PDGF-BB from nano-nacre/PDLLA/FG composite scaffold. Methods 24 New Zealand white rabbits which bilateral radius were resected into 15 mm bone defect, were divided into 4 groups randomly. The PDLLA scaffold was implanted through open operation into the bone defects in Group A, Group B was implanted with n-Nacre/PDLLA scaffold, Group C was implanted with controlled release of PDGF-BB from n-Nacre/PDLLA/FG composite scaffold, and control group without any implant. The specimens were examined after 4, 8, 12 weeks; the osteogenesis was evaluated through gross observation, X-ray radiograph, bone mineral density(BMD) examination, Micro-CT 3D reconstruction and histological examination. Results Gross observation found no repair but sclerosis of bone ends in control group while different extents of bone repair were observed in the other 3 groups. According to Lane-Sandhu X-ray criteria, Lane-Sandhu scores of Group C were much higher than Group B at 4, 8 and 12 weeks(P<0.05); Lane-Sandhu scores of Group B were much higher than Group A and control group at 4, 8 and 12 weeks(P<0.01). The BMD values of Group C were much higher than Group A and B at 4, 8 and 12 weeks(P<0.05). Micro-CT and histological examination suggested that Group C repair bone defect result was better than Group A and B. Conclusion Controlled release of PDGF-BB from n-Nacre/PDLLA/FG composite scaffold can contribute to osteogenesis during the repair of rabbit radius defect.
Objective To evaluate the effect of bone defect repair using the controlled release of PDGF-BB from nano-nacre/PDLLA/FG composite scaffold. Methods 24 New Zealand white rabbits which bilateral radius were resected into 15 mm bone defect, were divided into 4 groups randomly. The PDLLA scaffold was implanted through open operation into the bone defects in Group A, Group B was implanted with n-Nacre/PDLLA scaffold, Group C was implanted with controlled release of PDGF-BB from n-Nacre/PDLLA/FG composite scaffold, and control group without any implant. The specimens were examined after 4, 8, 12 weeks; the osteogenesis was evaluated through gross observation, X-ray radiograph, bone mineral density(BMD) examination, Micro-CT 3D reconstruction and histological examination. Results Gross observation found no repair but sclerosis of bone ends in control group while different extents of bone repair were observed in the other 3 groups. According to Lane-Sandhu X-ray criteria, Lane-Sandhu scores of Group C were much higher than Group B at 4, 8 and 12 weeks(P<0.05); Lane-Sandhu scores of Group B were much higher than Group A and control group at 4, 8 and 12 weeks(P<0.01). The BMD values of Group C were much higher than Group A and B at 4, 8 and 12 weeks(P<0.05). Micro-CT and histological examination suggested that Group C repair bone defect result was better than Group A and B. Conclusion Controlled release of PDGF-BB from n-Nacre/PDLLA/FG composite scaffold can contribute to osteogenesis during the repair of rabbit radius defect.
引文
[1]肖文德,陈建庭,张建刚,等.缓释PDGF-BB的纳米珍珠层/聚乳酸/纤维蛋白胶复合支架的制备[J].中国矫形外科杂志,2011,19(11):943-946.
[2]肖文德,陈建庭,徐准,等.缓释PDGF-BB的纳米珍珠层/聚乳酸/纤维蛋白胶复合支架的细胞相容性研究[J].中国骨与关节损伤杂志,2011,26(12):25-27.
[3]肖文德,郭东明,温世锋,等.缓释PDGF-BB的纳米珍珠层/聚乳酸/纤维蛋白胶复合支架生物安全性评价[J].中国骨与关节损伤杂志,2013,28(11):1038-1040.
[4]Xiao WD,Zhong ZM,Tang YZ,et al.The repair of critical size bone defects with porous poly(D,L-lactide)/nacre nanocomposite hollow scaffold[J].Saudi Med J,2012,33(6):179-185.
[5]Lane JM,Sandhu HS.Current approaches to experimental bone grafting[J].Orthop Clin North Am,1987,18(2):213-225.
[6]Kr?ger N.The molecular basis of nacre formation[J].Science,2009,325(5946):1351-1352.
[7]Metzler RA,Evans FS,Killian CE,et al.Nacre protein fragment templates lamellar aragonite growth[J].J Am Chem Soc,2010,132(18):6329-6334.
[8]黄千里,刘渊声,冯庆玲.珍珠层,一种具有潜力的天然骨修复材料[J].中国材料进展,2013,32(10):591-598.
[9]Lopez E,Vidal B,Berland S,et al.Demonstration of the capacity of nacre to induce bone formation by human osteoblasts maintained in vitro[J].Tissue Cell,1992,24(5):667-679.
[10]Liu YS,Huang QL,Kienzle A,et al.In vitro degradation of porous PLLA/pearl powder composite scaffolds[J].Mater Sci Eng C Mater Biol Appl,2014,1(38):227-234.
[11]Liu Y,Huang Q,Feng Q.3D scaffold of PLLA/pearl and PLLA/nacre powder for bone regeneration[J].Biomedical Materials,2013,8(6):5001-5009.
[12]Flausse A,Henrionnet C,Dossot M,et al.Osteogenic differentiation of human bone marrow mesenchymal stem cells in hydrogel containing nacre powder[J].J Biomed Mater Res A,2013,101(11):3211-3218.
[13]Chaturvedi R,Singha PK,Dey S.Water soluble bioactives of nacre mediate antioxidant activity and osteoblast differentiation[J].PLo S One,2013,8(12):1-10.
[14]Mezawa M,Araki S,Takai H,et al.Regulation of human bone sialoprotein gene transcription by platelet-derived growth factor-BB[J].Gene,2009,435(1/2):80-87.
[15]Kubota K,Sakikawa C,Katsumata M,et al.Platelet-derived growth factor BB secreted from osteoclasts acts as an osteoblastogenesis inhibitory factor[J].J Bone Miner Res,2002,17(2):257-265.
[16]Al-Zube L,Breitbart EA,O'Connor JP,et al.Recombinant human platelet-derived growth factor BB(rh PDGF-BB)and beta-tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model[J].J Orthop Res,2009,27(8):1074-1081.
[17]Hollinger JO,Onikepe AO,Mac Krell J,et al.Accelerated fracture healing in the geriatric,osteoporotic rat with recombinant human platelet-derived growth factor-BB and an injectable beta-tricalcium phosphate/collagen matrix[J].J Orthop Res,2008,26(1):83-90.
[2]肖文德,陈建庭,徐准,等.缓释PDGF-BB的纳米珍珠层/聚乳酸/纤维蛋白胶复合支架的细胞相容性研究[J].中国骨与关节损伤杂志,2011,26(12):25-27.
[3]肖文德,郭东明,温世锋,等.缓释PDGF-BB的纳米珍珠层/聚乳酸/纤维蛋白胶复合支架生物安全性评价[J].中国骨与关节损伤杂志,2013,28(11):1038-1040.
[4]Xiao WD,Zhong ZM,Tang YZ,et al.The repair of critical size bone defects with porous poly(D,L-lactide)/nacre nanocomposite hollow scaffold[J].Saudi Med J,2012,33(6):179-185.
[5]Lane JM,Sandhu HS.Current approaches to experimental bone grafting[J].Orthop Clin North Am,1987,18(2):213-225.
[6]Kr?ger N.The molecular basis of nacre formation[J].Science,2009,325(5946):1351-1352.
[7]Metzler RA,Evans FS,Killian CE,et al.Nacre protein fragment templates lamellar aragonite growth[J].J Am Chem Soc,2010,132(18):6329-6334.
[8]黄千里,刘渊声,冯庆玲.珍珠层,一种具有潜力的天然骨修复材料[J].中国材料进展,2013,32(10):591-598.
[9]Lopez E,Vidal B,Berland S,et al.Demonstration of the capacity of nacre to induce bone formation by human osteoblasts maintained in vitro[J].Tissue Cell,1992,24(5):667-679.
[10]Liu YS,Huang QL,Kienzle A,et al.In vitro degradation of porous PLLA/pearl powder composite scaffolds[J].Mater Sci Eng C Mater Biol Appl,2014,1(38):227-234.
[11]Liu Y,Huang Q,Feng Q.3D scaffold of PLLA/pearl and PLLA/nacre powder for bone regeneration[J].Biomedical Materials,2013,8(6):5001-5009.
[12]Flausse A,Henrionnet C,Dossot M,et al.Osteogenic differentiation of human bone marrow mesenchymal stem cells in hydrogel containing nacre powder[J].J Biomed Mater Res A,2013,101(11):3211-3218.
[13]Chaturvedi R,Singha PK,Dey S.Water soluble bioactives of nacre mediate antioxidant activity and osteoblast differentiation[J].PLo S One,2013,8(12):1-10.
[14]Mezawa M,Araki S,Takai H,et al.Regulation of human bone sialoprotein gene transcription by platelet-derived growth factor-BB[J].Gene,2009,435(1/2):80-87.
[15]Kubota K,Sakikawa C,Katsumata M,et al.Platelet-derived growth factor BB secreted from osteoclasts acts as an osteoblastogenesis inhibitory factor[J].J Bone Miner Res,2002,17(2):257-265.
[16]Al-Zube L,Breitbart EA,O'Connor JP,et al.Recombinant human platelet-derived growth factor BB(rh PDGF-BB)and beta-tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model[J].J Orthop Res,2009,27(8):1074-1081.
[17]Hollinger JO,Onikepe AO,Mac Krell J,et al.Accelerated fracture healing in the geriatric,osteoporotic rat with recombinant human platelet-derived growth factor-BB and an injectable beta-tricalcium phosphate/collagen matrix[J].J Orthop Res,2008,26(1):83-90.