纳米骨胶的实验研究
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摘要
【目的】
随着交通及高空建筑事业的发展,严重四肢骨折日渐增多,其中,四肢严重粉碎性骨折的治疗是当前骨科领域中的一个难题,采用常规内固定方法有时很难达到满意的程度,常常导致骨不连、骨延迟愈合或畸形愈合,严重乃至永久伤残。利用组织工程原理结合纳米技术研究骨科用胶黏剂以解决当前严重的粉碎性骨折的治疗是目前研究的难点与热点问题。本项目基于改进α-氰基丙烯酸正丁酯合成工艺条件的基础上,采用纳米技术,加入纳米催化剂及纳米硫酸钙固化剂,在增粘、增韧及调整体内降解时间等方面进行改性研究,提高其胶液粘度和调整降解时间,再与具有骨诱导活性的淫羊藿素复合,制备出可吸收的具有骨诱导作用的高分子纳米生物骨胶,使其拥有骨折固定和骨诱导双重特性。纳米骨胶可解决目前骨粘合剂粘度低、力学性能差、不易吸收及不具有骨诱导活性的关键技术问题。用该强力骨胶固定碎骨块,将为粉碎性骨折的治疗带来全新的方法,必将带来重大的社会效益和经济效益。
【方法】
1、配胶
(1)配胶,观察硫酸钙粉末加入胶中是否瞬间凝固;
(2)动物骨检测胶黏性,生物力学测试比较不同浓度胶的胶黏强度;
(3)统计分析选出最合适的胶作为体内外试验用。
2、细胞毒性实验
与普通医用胶进行对比,直接在普通胶和纳米骨胶上种植兔骨髓基质干细胞,通过倒置显微镜和扫描电镜观察细胞在胶上生长情况。用胶的浸泡液行高效液相色谱法检测毒性物质,并用浸泡液培养细胞,在0,6,12,18,24h时间点和1-7天每天进行细胞活性检测。用两种胶将标准聚氯乙烯硬质管粘合,比较两种胶的粘合强度,并在不同环境下比较胶凝固时间
(1)铺板与植入细胞;
(2)高效液相色谱法监测不同时间点浸泡液中胶释放物质的浓度变化;
(3)提取浸泡液培养细胞,观察细胞在短期(24h内)和长期(7天)的增殖情况,进行细胞活性测定和MTT细胞毒性检测;
(4)扫描电镜观察细胞与胶附着情况;
(5)胶黏力学测试和凝固时间比较。
3、动物实验
(1)按不同胶成分分为五组(两种添加剂分别与纯胶混合):
(2)50只兔手术造成双尺骨中段横行骨折,分别用五组不同成分胶固定骨折;
(3)术后于2-12周每两周一次X线对比,2、6、8、12周定期处死兔子,行生物力学,microCT,组织病理学检查等。
【结果】
1、配胶
(1)纳米硫酸钙与胶混合,粉末可与胶形成均匀悬浊液,粉末不会凝结成小块状沉淀,且随粉末浓度的增加,胶仍为液态,粘滞度未发生明显改变;
(2)胶黏:不同浓度硫酸钙胶的粘合速度无明显差异。力学检测显示随纳米硫酸钙浓度增加胶粘合力呈抛物线趋势,纳米硫酸钙浓度为10%时,胶的平均力学强度最大。
2、细胞毒性实验
(1)经三次换液,普通胶与纳米骨胶上细胞均能存活,两种胶都有一级细胞毒性,毒性无显著差别;
(2)纳米骨胶的力学强度明显高于普通胶,且凝固时间明显快于普通胶。
3、动物实验
(1)X线片、组织病理学示:12周时GⅠ和GⅤ胶粘合的骨折均已愈合,骨髓腔贯通,GⅢ、GⅣ骨折基本愈合,髓腔未完全贯通,较前两组愈合缓慢,GⅡ骨折愈合慢,髓腔未通。
(2)MicroCT示:6周时GⅠ和GⅤ骨折处骨性骨痂形成较多,骨折愈合良好;GⅢ、GⅣ次之;GⅡ骨折愈合较差。
(3)力学测验:12周时组间GⅠ和GⅤ无显著差别,但均大于GⅢ、GⅣ,GⅡ力学强度最低。
【结论】
1. 10%浓度的纳米硫酸钙胶的胶黏强度最大;
2.经改性后的纳米骨胶细胞毒性不高于普通胶,但力学强度和凝固时间前者明显优于后者,且前者具有促进成骨的作用。
3.纳米骨胶不会延迟骨的愈合;与普通医用胶相比,可增加胶黏强度,促进骨折愈合,有望成为一种新型、效果理想的骨折修复材料,可在临床中得到广泛运用。
【Objective】
As the development of traffic and bungee construction, the incidence of serious extremities fracture is increasing gradually, in which the treatment of grievous comminuted fractured is still the field of orthopeadics to be one of challenges at present. The traditional internal fixation that could lead to non-union,delayed union and malunion of bone, even permanent disability to patients is hard to satisfy. Nowadays, the difficult and hot spots are histological engineering combined with nanotechnology to research the internal fixation materials in clinic to crue the stress communited fracture. Our project is based on the modified synthetic technology ofα-Butyl cyanoacrylate, by nanotechnology, mixed with nanometercatalyst and nCS. Researched from adhesive strength and biodegradation rate, these features of bone glue are improved. Recombined with osteoinductived icartin, the absorbable and osteoinductived macromolecule nano-bone adhesive with both characters-fixation and osteoinduction has been manufactured. This task could resolve the critical technical issues of existing bone adhesive, such as low viscosity, weak mechanical property, less easily absorbtion and without osteoinduction. Fixation bone fragments with this mighty glue will be a new method of comminuted fracture and bring some grand social effect and economic benefit.
【Methods】
1. Glue prescription
(1) Observed that the glue mixed with nCS powder congeal instantly or not;
(2) Texted the agglutinate character using animal bone and compared with the adhesive strength of some kinds of glue with different concentration;
(3) Choosed the best bone glue by statistical analysis for experiment in vivo and vitro.
2. The cytotoxicity experiment Rabbit bone marrow stromal stem cells were directly implanted with nano-bone adhesive and common medical glue, the growth of these cells on the surface of the two glues was observed by inverted microscope and scanning electron microscope. The extracting solution of the two glues was collected to culture cells. At 0, 6, 12, 18, 24 hours (short-term assay, viability) and 1-7 days (long-term assay, survival), the cells were examined everyday. Standard polyvinyl chloride tubes were cohered by the two glues respectively, to compare their adhesive strength. Their consolidation time on different contract surfaces was also accounted.
(1) Glue planked and cells implanted;
(2) Monitored the concentration of some substance delivered from the glue at different time spot by HPLC;
(3) The extracting solution of the two glues was collected to culture cells. At 0, 6, 12, 18, 24 hours (short-term assay, viability) and 1-7 days (long-term assay, survival), the cells were examined everyday;
(4) Observed the growth of these cells on the surface of the two glues by SEM;
(5) Tested the adhesive strength and compared the consolidation time.
3.Animal experiment
(1) Divided into five groups according to different constituents of the glue (two kinds of additive mixed with pure glue):
(2) Operated 50 rabbits to make the models of bilateral ulnas fracture and fixed with 5 groups glue respectively.
(3) At afteroperation, X-ray performed every 2 weeks in 2-12 weeks and put the rabbits to death at 2nd week, 6th week, 8th week and 12th week to carry out biomechanical analysis, microCT scanning and histopathology study.
【Results】
1. Glue prescription
(1) Blended nCS and pure glue could lead to a well-distributed auspended matter. The nCS powders will not concrete and with the concentration increasing, the mixture was still liquid state and viscosity didn’t change;
(2) Agglutinate character: the consolidation time of adhesive of different glues were not significant difference, and the biomechanical presents a parabola with the nCS increasing. When the concentration was 10%, the most average adhesive strength took on.
2. The cytotoxicity experiment
(1) After three times of culture medium replacement, the cells can be grow on the surface of nano-bone adhesive and medical glue. Both had some cytotoxicity that was not significant difference.
(2) The mechanical strength of nano-bone adhesive was stronger than the medical glue, and the consolidation time of the former was also faster than the latter.
3.Animal experiment
(1) X-Ray, histopathology showed that at 12th week, unlas fracture of GⅠand GⅤhave healed and medullary cavity have been unobstructed, however, GⅢand GⅣhave not healed completely, inferior than GⅠand GⅤ. The delayed union took placed in GⅢ.
(2) At 6th week, microCT took on that bony callus around fractures of GⅠand GⅤis at most, inferior in GⅢand GⅣ, least in GⅡ.
(3) Biomechanical strength of GⅠand GⅤis not significant difference at 12th week, but stronger than GⅢand GⅣand GⅡis the weakest.
【Conclusion】
1. The strongest adhesive strength is that the concentration of nCS in nano-bond is 10%.
2. The cytotoxicity of modified nano-bone adhesive is not higher than the medical glue, but the mechanical strength and consolidation are more superior. The former also can stimulate the ossification.
3. The nano-bone adhesive can’t lead to fractures delayed union; Compared with traditional medical glue, its mechanical strength is stronger and it will promote fracture healing. So, the nano-bone adhesive is expected to become an ideal material for repairing bone fracture, and get extensive application in clinic.
随着交通及高空建筑事业的发展,严重四肢骨折日渐增多,其中,四肢严重粉碎性骨折的治疗是当前骨科领域中的一个难题,采用常规内固定方法有时很难达到满意的程度,常常导致骨不连、骨延迟愈合或畸形愈合,严重乃至永久伤残。利用组织工程原理结合纳米技术研究骨科用胶黏剂以解决当前严重的粉碎性骨折的治疗是目前研究的难点与热点问题。本项目基于改进α-氰基丙烯酸正丁酯合成工艺条件的基础上,采用纳米技术,加入纳米催化剂及纳米硫酸钙固化剂,在增粘、增韧及调整体内降解时间等方面进行改性研究,提高其胶液粘度和调整降解时间,再与具有骨诱导活性的淫羊藿素复合,制备出可吸收的具有骨诱导作用的高分子纳米生物骨胶,使其拥有骨折固定和骨诱导双重特性。纳米骨胶可解决目前骨粘合剂粘度低、力学性能差、不易吸收及不具有骨诱导活性的关键技术问题。用该强力骨胶固定碎骨块,将为粉碎性骨折的治疗带来全新的方法,必将带来重大的社会效益和经济效益。
【方法】
1、配胶
(1)配胶,观察硫酸钙粉末加入胶中是否瞬间凝固;
(2)动物骨检测胶黏性,生物力学测试比较不同浓度胶的胶黏强度;
(3)统计分析选出最合适的胶作为体内外试验用。
2、细胞毒性实验
与普通医用胶进行对比,直接在普通胶和纳米骨胶上种植兔骨髓基质干细胞,通过倒置显微镜和扫描电镜观察细胞在胶上生长情况。用胶的浸泡液行高效液相色谱法检测毒性物质,并用浸泡液培养细胞,在0,6,12,18,24h时间点和1-7天每天进行细胞活性检测。用两种胶将标准聚氯乙烯硬质管粘合,比较两种胶的粘合强度,并在不同环境下比较胶凝固时间
(1)铺板与植入细胞;
(2)高效液相色谱法监测不同时间点浸泡液中胶释放物质的浓度变化;
(3)提取浸泡液培养细胞,观察细胞在短期(24h内)和长期(7天)的增殖情况,进行细胞活性测定和MTT细胞毒性检测;
(4)扫描电镜观察细胞与胶附着情况;
(5)胶黏力学测试和凝固时间比较。
3、动物实验
(1)按不同胶成分分为五组(两种添加剂分别与纯胶混合):
(2)50只兔手术造成双尺骨中段横行骨折,分别用五组不同成分胶固定骨折;
(3)术后于2-12周每两周一次X线对比,2、6、8、12周定期处死兔子,行生物力学,microCT,组织病理学检查等。
【结果】
1、配胶
(1)纳米硫酸钙与胶混合,粉末可与胶形成均匀悬浊液,粉末不会凝结成小块状沉淀,且随粉末浓度的增加,胶仍为液态,粘滞度未发生明显改变;
(2)胶黏:不同浓度硫酸钙胶的粘合速度无明显差异。力学检测显示随纳米硫酸钙浓度增加胶粘合力呈抛物线趋势,纳米硫酸钙浓度为10%时,胶的平均力学强度最大。
2、细胞毒性实验
(1)经三次换液,普通胶与纳米骨胶上细胞均能存活,两种胶都有一级细胞毒性,毒性无显著差别;
(2)纳米骨胶的力学强度明显高于普通胶,且凝固时间明显快于普通胶。
3、动物实验
(1)X线片、组织病理学示:12周时GⅠ和GⅤ胶粘合的骨折均已愈合,骨髓腔贯通,GⅢ、GⅣ骨折基本愈合,髓腔未完全贯通,较前两组愈合缓慢,GⅡ骨折愈合慢,髓腔未通。
(2)MicroCT示:6周时GⅠ和GⅤ骨折处骨性骨痂形成较多,骨折愈合良好;GⅢ、GⅣ次之;GⅡ骨折愈合较差。
(3)力学测验:12周时组间GⅠ和GⅤ无显著差别,但均大于GⅢ、GⅣ,GⅡ力学强度最低。
【结论】
1. 10%浓度的纳米硫酸钙胶的胶黏强度最大;
2.经改性后的纳米骨胶细胞毒性不高于普通胶,但力学强度和凝固时间前者明显优于后者,且前者具有促进成骨的作用。
3.纳米骨胶不会延迟骨的愈合;与普通医用胶相比,可增加胶黏强度,促进骨折愈合,有望成为一种新型、效果理想的骨折修复材料,可在临床中得到广泛运用。
【Objective】
As the development of traffic and bungee construction, the incidence of serious extremities fracture is increasing gradually, in which the treatment of grievous comminuted fractured is still the field of orthopeadics to be one of challenges at present. The traditional internal fixation that could lead to non-union,delayed union and malunion of bone, even permanent disability to patients is hard to satisfy. Nowadays, the difficult and hot spots are histological engineering combined with nanotechnology to research the internal fixation materials in clinic to crue the stress communited fracture. Our project is based on the modified synthetic technology ofα-Butyl cyanoacrylate, by nanotechnology, mixed with nanometercatalyst and nCS. Researched from adhesive strength and biodegradation rate, these features of bone glue are improved. Recombined with osteoinductived icartin, the absorbable and osteoinductived macromolecule nano-bone adhesive with both characters-fixation and osteoinduction has been manufactured. This task could resolve the critical technical issues of existing bone adhesive, such as low viscosity, weak mechanical property, less easily absorbtion and without osteoinduction. Fixation bone fragments with this mighty glue will be a new method of comminuted fracture and bring some grand social effect and economic benefit.
【Methods】
1. Glue prescription
(1) Observed that the glue mixed with nCS powder congeal instantly or not;
(2) Texted the agglutinate character using animal bone and compared with the adhesive strength of some kinds of glue with different concentration;
(3) Choosed the best bone glue by statistical analysis for experiment in vivo and vitro.
2. The cytotoxicity experiment Rabbit bone marrow stromal stem cells were directly implanted with nano-bone adhesive and common medical glue, the growth of these cells on the surface of the two glues was observed by inverted microscope and scanning electron microscope. The extracting solution of the two glues was collected to culture cells. At 0, 6, 12, 18, 24 hours (short-term assay, viability) and 1-7 days (long-term assay, survival), the cells were examined everyday. Standard polyvinyl chloride tubes were cohered by the two glues respectively, to compare their adhesive strength. Their consolidation time on different contract surfaces was also accounted.
(1) Glue planked and cells implanted;
(2) Monitored the concentration of some substance delivered from the glue at different time spot by HPLC;
(3) The extracting solution of the two glues was collected to culture cells. At 0, 6, 12, 18, 24 hours (short-term assay, viability) and 1-7 days (long-term assay, survival), the cells were examined everyday;
(4) Observed the growth of these cells on the surface of the two glues by SEM;
(5) Tested the adhesive strength and compared the consolidation time.
3.Animal experiment
(1) Divided into five groups according to different constituents of the glue (two kinds of additive mixed with pure glue):
(2) Operated 50 rabbits to make the models of bilateral ulnas fracture and fixed with 5 groups glue respectively.
(3) At afteroperation, X-ray performed every 2 weeks in 2-12 weeks and put the rabbits to death at 2nd week, 6th week, 8th week and 12th week to carry out biomechanical analysis, microCT scanning and histopathology study.
【Results】
1. Glue prescription
(1) Blended nCS and pure glue could lead to a well-distributed auspended matter. The nCS powders will not concrete and with the concentration increasing, the mixture was still liquid state and viscosity didn’t change;
(2) Agglutinate character: the consolidation time of adhesive of different glues were not significant difference, and the biomechanical presents a parabola with the nCS increasing. When the concentration was 10%, the most average adhesive strength took on.
2. The cytotoxicity experiment
(1) After three times of culture medium replacement, the cells can be grow on the surface of nano-bone adhesive and medical glue. Both had some cytotoxicity that was not significant difference.
(2) The mechanical strength of nano-bone adhesive was stronger than the medical glue, and the consolidation time of the former was also faster than the latter.
3.Animal experiment
(1) X-Ray, histopathology showed that at 12th week, unlas fracture of GⅠand GⅤhave healed and medullary cavity have been unobstructed, however, GⅢand GⅣhave not healed completely, inferior than GⅠand GⅤ. The delayed union took placed in GⅢ.
(2) At 6th week, microCT took on that bony callus around fractures of GⅠand GⅤis at most, inferior in GⅢand GⅣ, least in GⅡ.
(3) Biomechanical strength of GⅠand GⅤis not significant difference at 12th week, but stronger than GⅢand GⅣand GⅡis the weakest.
【Conclusion】
1. The strongest adhesive strength is that the concentration of nCS in nano-bond is 10%.
2. The cytotoxicity of modified nano-bone adhesive is not higher than the medical glue, but the mechanical strength and consolidation are more superior. The former also can stimulate the ossification.
3. The nano-bone adhesive can’t lead to fractures delayed union; Compared with traditional medical glue, its mechanical strength is stronger and it will promote fracture healing. So, the nano-bone adhesive is expected to become an ideal material for repairing bone fracture, and get extensive application in clinic.
引文
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[22]. Jian Huang, Lan Yuan, Xi Wang, et al. Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro. Life Sciences, 2007, 87:832–840.
[23].Guarnieri R, Grassi R, Ripari M, et al. Maxillary sinus augmentation using granular calcium sulfate (surgiplaster sinus): Radiographic and histologic studyat 2 years. Int J Periodontics Restorative Dent, 2006,26:79–85.
[24].Scarano A, Orsini G, Pecora G, et al. Peri-implant bone regeneration with calcium sulfate: A light and transmission electron microscopy case report. Implant Dent, 2007,16:195–203.
[25].Saeed Hesaraki, Roghayeh Nemati, Hamid Nazarian. Physico–Chemical and In Vitro Biological Study of Zinc-Doped Calcium Sulfate Bone Substitute. Wiley InterScience, 2009,2:37-45.
[26]. Christopher L.Peters, Jerod L.Hines, Kent N.Bachus. et al. Biological effects of calcium sulfate as a bone graft substitute in ovine metaphyseal defects. Wiley InterScience, 2005, 456-462.
[27]. Mark V. Thomas, David A. Puleo. Calcium Sulfate: Properties and Clinical Applications. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2008, 7:597-610.
[28]. Yin Xiao-xue, Chen Zhong-qiang, Liu Zhong-jun, et al. Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2. Chin Med J, 2007, 120(3):204-210.
[29]. Guo-feng Qian, Xiu-zhen Zhang, Li-xia LU, et al. Regulation of Cbfa1 expression by Total Flavonoids of Herba Epimedii. Endocrine Journal, 2006, 53(1):87-94.
[30]. McClung, M.R., 2006. Inhibition of RANKL as a treatment for osteoporosis: preclinical and early clinical studies. Current Osteoporosis Reports 4, 28–33.
[31]. Claudia A. Reicheneder, Tomas Gedrange, Alexandra Lange, et al. Shear and tensile bond strength comparison of various contemporary orthodontic adhesive systems: An in-vitro study. Am J Orthod Dentofacial Orthop 2009,35:422-423.
[32]. Stephen J. Ferguson, Urs Weber, Brigitte von Rechenberg, et al. Enhancing the Mechanical Integrity of the Implant–Bone Interface With BoneWelding Technology: Determination of Quasi-Static Interfacial Strength and Fatigue Resistance. Wiley InterScience 2005,6:13-20.
[33]. Mona I. Winge, Olav Reiker?s, Magne R?kkum. Calcium phosphate bone cement: a possible alternative to autologous bone graft. A radiological andbiomechanical comparison in rat tibial bone. Arch Orthop Trauma Surg,2010,12:200-207
[34]. Alexander S. Spiro, F. Timo Beil, Anke Baranowsky. BMP-7–Induced Ectopic Bone Formation and Fracture Healing Is Impaired by Systemic NSAID Application in C57BL/6-Mice. JOURNAL OF ORTHOPAEDIC RESEARCH,2011,6:785-791.
[35]. Marcus Egermann, Petra Heil, Andrea Tami. Influence of Defective Bone Marrow Osteogenesis on Fracture Repair in an Experimental Model of Senile Osteoporosis. JOURNAL OF ORTHOPAEDIC RESEARCH,2011,6:798-804.
[36]. Tohru Hayakawa, Chihiro Mochizuki, Hiroki Hara. In vivo evaluation of composites of PLGA and apatite with two different levels of crystallinity. J Mater Sci: Mater Med, 2010,21:251–258.
[37]. Daniel Toben, Ireen Schroeder, Thaqif El Khassawna, et al. Fracture Healing Is Accelerated in the Absence of the Adaptive Immune System. American Society for Bone and Mineral Research, 2011,1:113-124.
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[1].田霞,卢永顺.福爱乐医用胶(FAL)及其应用.国际外科学杂志2006, 33(2):145-149.
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[21].李春梅,罗康碧,李沪萍,等.硫酸钙微米/纳米材料的研究进展.化工科技, 2009, 17(4):57-60.
[22]. Jian Huang, Lan Yuan, Xi Wang, et al. Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro. Life Sciences, 2007, 87:832–840.
[23].Guarnieri R, Grassi R, Ripari M, et al. Maxillary sinus augmentation using granular calcium sulfate (surgiplaster sinus): Radiographic and histologic studyat 2 years. Int J Periodontics Restorative Dent, 2006,26:79–85.
[24].Scarano A, Orsini G, Pecora G, et al. Peri-implant bone regeneration with calcium sulfate: A light and transmission electron microscopy case report. Implant Dent, 2007,16:195–203.
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[29]. Guo-feng Qian, Xiu-zhen Zhang, Li-xia LU, et al. Regulation of Cbfa1 expression by Total Flavonoids of Herba Epimedii. Endocrine Journal, 2006, 53(1):87-94.
[30]. McClung, M.R., 2006. Inhibition of RANKL as a treatment for osteoporosis: preclinical and early clinical studies. Current Osteoporosis Reports 4, 28–33.
[31]. Claudia A. Reicheneder, Tomas Gedrange, Alexandra Lange, et al. Shear and tensile bond strength comparison of various contemporary orthodontic adhesive systems: An in-vitro study. Am J Orthod Dentofacial Orthop 2009,35:422-423.
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[33]. Mona I. Winge, Olav Reiker?s, Magne R?kkum. Calcium phosphate bone cement: a possible alternative to autologous bone graft. A radiological andbiomechanical comparison in rat tibial bone. Arch Orthop Trauma Surg,2010,12:200-207
[34]. Alexander S. Spiro, F. Timo Beil, Anke Baranowsky. BMP-7–Induced Ectopic Bone Formation and Fracture Healing Is Impaired by Systemic NSAID Application in C57BL/6-Mice. JOURNAL OF ORTHOPAEDIC RESEARCH,2011,6:785-791.
[35]. Marcus Egermann, Petra Heil, Andrea Tami. Influence of Defective Bone Marrow Osteogenesis on Fracture Repair in an Experimental Model of Senile Osteoporosis. JOURNAL OF ORTHOPAEDIC RESEARCH,2011,6:798-804.
[36]. Tohru Hayakawa, Chihiro Mochizuki, Hiroki Hara. In vivo evaluation of composites of PLGA and apatite with two different levels of crystallinity. J Mater Sci: Mater Med, 2010,21:251–258.
[37]. Daniel Toben, Ireen Schroeder, Thaqif El Khassawna, et al. Fracture Healing Is Accelerated in the Absence of the Adaptive Immune System. American Society for Bone and Mineral Research, 2011,1:113-124.
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[1].田霞,卢永顺.福爱乐医用胶(FAL)及其应用.国际外科学杂志2006, 33(2):145-149.
[2]. Shapiro AJ, Dinsmore RC, North JH. Tensile strength of wound clousure with cyanoacrylate glue. Am Surg, 2001, 67(11):1113.
[3]. S. Saska, E. Hochuli-Vieira, A. M. Minarelli-Gaspar, et al. Fixation of autogenous bone grafts with ethyl-cyanoacrylate glue or titanium screws in the calvaria of rabbits. Oral and Maxillofacial Surgery, 2009, 38:180-186.
[4]. Giray CB, Sungur A, Atasever A, et al. Comparasion of silk sutures and n-butyl-2-cyanoacrylate on the healing of skin wounds. A pilot study. Aust Dental J, 1995, 40: 43–45.
[5]. Singer AJ, Thode Jr HC. A review of the literature on octyl-cyanoacrylate tissue adhesive. Am J Surg, 2004, 187: 238–248.
[6]. Suuronen R, Kontio R, Ashammakhi N, et al. Bioabsorbable self-reinforced plates and screws in craniomaxillofacial surgery. Biomed Mater Eng, 2004, 14:517–522.
[7]. Pe′rez M, Ferna′ndez I, Ma′rquez D, et al. Use of n-butyl-cyanoacrylate on oral surgery: biological and clinical evaluation. Artif Organs, 2000, 24: 241–243.
[8]. Reece TB, Maxey TS, Kron IL. A prospectus on tissue adhesives. Am J Surg, 2001, 182: 40S–44S.
[9]. Azevedo CL, Marques MM, Bombana AC. Cytotoxic effects of cyanoacrylates used as retrograde filling materials: an in vitro analysis. Pesq Odontol Bras, 2003, 17: 113–118.
[10]. Tong L, Buchman SR. Facial bone grafts: contemporary science and thought. J Cranio-maxillo Trauma, 2000, 6: 31–41.
[11]. Y?lmaz C, Kuyurtar F. Fixation of a talar osteochondral fracture with cyanoacrylate glue. Arthroscopy, 2005, 21:1009.
[12]. Burhan Dadas, Seyhan Alkan, Memet Cifci, et al. Treatment of tripod fracture of zygomatic bone by N-2-butyl cyanoacrylate glue fixation, and its effects on the tissues. Eur Arch Otorhinolaryngol, 2007, 264:539–544.
[13].王亦璁.骨与关节损伤.人民卫生出版社. 2007.10:186-187.
[14].吕波,屠重琪,裴福兴,等.医用硬组织黏接胶黏接胫骨中段蝶形骨折的生物力学研究.生物医学工程学杂志, 2004, 21(3):359-362.
[15]. Bishara SE, Laffoon JF, Vonwald L, et al. The effect of repeated bonding on the shear bond strength of different orthodontic adhesives. Am J Orthod Dentofacial Orthop, 2002, 121(5):52.
[16].吕波,裴福兴,屠重琪,等.α-氰基丙烯酸正辛酯反复粘接人胫骨皮质骨的生物力学研究.生物医学工程学杂志, 2007, 24(2):308-311.
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