人发角蛋白复合聚乳酸骨折内固定材料的实验研究
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摘要
由于生物可吸收内固定器材在骨科手术中具有金属材料所无法比拟的优势，故是近30年国内外学者研究的热门。但由于材料和工艺上的问题，初始机械力学性能低，早期降解速度快，只能用于非承重骨的内固定，而不能用于四肢长管状骨的固定。本研究总结国内外学者的研究经验，以人发角蛋白(Human Hair Keratin, HHK)与医用聚乳酸(Polyactic Acid, PLA)为原料，按一定比例机械加工制成人发角蛋白复合聚乳酸(HHK-PLA)骨折内固定棒，对其进行相关检测及观察，为进一步研究和临床应用提供实验依据。
【目的】
1．对自行研究的人发角蛋白复合聚乳酸(HHK-PLA)骨折内固定棒进行机械力学强度测试，分别测量HHK-PLA棒的剪切力和我三点弯曲力，计算其剪切强度、弯曲强度和弯曲模量。
2．了解人发角蛋白复合聚乳酸(HHK-PLA)骨折内固定棒的体内降解情况，对不同阶段的降解速度进行观察。
3．对人发角蛋白复合聚乳酸(HHK-PLA)骨折内固定棒的生物相容性进行初步观察。
【方法】
1．利用MTS-858 Mini Bionix型生物力学测试机对20根人发角蛋白复合聚乳酸(HHK-PLA)骨折内固定棒进行测试，包括剪切强度和弯曲力，并计算剪切强度、弯曲强度和弯曲模量。
2．36个HHK-PLA试件随机植入18只SD大鼠背部脊旁皮下组织中，分别于术后1、2、4、8、12、16、20、24、28周取出，测量重量损失，了解HHK-PLA在SD大鼠体内的降解情况。扫描电镜(SEM)下观察HHK-PLA试件降解后的结构变化。
3.切取HHK一PLA试件周围的大鼠组织，制作组织切片，观察组织
的炎症反应情况，了解HHK一PLA材料的生物相容性。
【结果】
1.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒具有良好的
初始机械力学强度，其剪切强度为24lMpa，弯曲强度为358MPa，弯曲
模量为13Gpa。
2.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒的体内降解
属性良好，早期降解速度缓慢，而后期降解速度较快。
3.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒植入大鼠体
内1一2周，其周围有明显的纤维组织包裹，结缔组织增生，其间毛细血
管扩张、充血，巨噬细胞、浆细胞、中性粒细胞、成纤维细胞和单核细
胞浸润。8周后HHK一PLA试件周围组织炎症反应逐步减轻。术后12周，
HHK一PLA试件周围组织异物反应基本消失，没有炎症细胞浸润。
【结论】
1.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒具有良好的
初始机械力学强度，能够满足四肢骨的内固定要求。
2.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒的体内降解
属性良好，早期降解速度缓慢，而后期降解速度较快。这种体内降解的
特点有利于骨折愈合，在骨折未愈合时，HHK一PLA基本没有降解，起到
强有力的固定作用，待骨折已经愈合，HHK一PLA开始逐渐降解。
3.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒具有良好的
生物相容性，早期为异物反应，8周后，异物反应逐步减轻，术后12周，
HHK一PLA试件周围组织异物反应基本消失。
Bioabsorbable internal fixation devices have become a focus of many researchers in the past 30 years because of their incomparable advantages to metal materials in orthopaedic operations. However, they can only be used for internal fixation of non weight-bearing bones as their low initial mechanical quality and rapid early period degradation, which originate from their material and technical characteristics. In this study, we summarized foreign and domestic data and produced a new kind of internal fixation rods (HHK-PLA rods), which is made of polyactic acid (PLA) and human hair keratin (HHK). Then, we performed corresponding tests and observation to obtain more evidences for further study and clinical applications. Objective:
1. Mechanical intensity tests were performed on the HHK-PLA rods, including the shearing force and the tri-points bending force, and then shearing strength, bending strength and elastic modulus were calculated.
2. To obtain the data of degradation of the HHK-PLA rods in vivo.
3. To observe the biocompatibility of the HHK-PLA rods. Methods:
1. A material testing machine (MTS 858 Bionix Material Testing System, MTS, Minneapolis, MN) was introduced to test 20 HHK-PLA rods.
2. 36 HHK-PLA rods were randomly transplanted into the hypodermis around the vertebra of 18 SD rats, two rods for each rat, and were taken out 1, 2, 4, 8, 12, 16, 20, 24 and 28 weeks after the operations respectively. And then, weight reduction of each rod was tested to be an indicator of the HHK-PLA rod degradation in vivo. At the same time, the constitution changes of the rods were also observed under the scanning
constitution changes of the rods were also observed under the scanning
electron microscope (SEM). 3. The tissue peripheral to the HHK-PLA rod was cut off and made into
tissue sections to observe the inflammatory reaction, which can indicate
the biocompatibility of the HHK-PLA rod. Results:
1. The HHK-PLA rod processed an outstanding initial mechanical quality, with 241MPa in shearing strength, 358MPa in bending strength and 13GPa in elastic modulus.
2. The degradation procedure of the HHK-PLA rods in vivo was very satisfying as it degraded slowly in the earlier period and went out fast in the anaphase.
3. 1 to 2 weeks after the transplantation, transparent fibrous tissue encapsulation and connective tissue proliferation were seen around the HHK-PLA rods, with the appearance of capillary telangiectasia and hyperemia and macrophage, plasmacyte, neutrophilic granulocyte, fibroblast and monocyte infiltration. The inflammatory reaction died off gradually after 8 weeks and by the end of 12 weeks after the transplantation, there were almost no foreign body reaction and inflammatory cell infiltration seen.
Conclusions:
1. The HHK-PLA rods can fully gratify the demands of internal fixation of limb bones.
2. The characteristic degradation behavior of the HHK-PLA rods was very advantageous to the healing of the fracture because, when in the earlier period, they can produce powerful fixation effects as they degraded little and, while in the anaphase, the rods broke down gradually as the bone itself could already take the place.
3. The HHK-PLA rods presented a satisfying biocompatibility. In the early period, the reaction was foreign body reaction and, after 12 weeks, no abnormality was seen.
【目的】
1．对自行研究的人发角蛋白复合聚乳酸(HHK-PLA)骨折内固定棒进行机械力学强度测试，分别测量HHK-PLA棒的剪切力和我三点弯曲力，计算其剪切强度、弯曲强度和弯曲模量。
2．了解人发角蛋白复合聚乳酸(HHK-PLA)骨折内固定棒的体内降解情况，对不同阶段的降解速度进行观察。
3．对人发角蛋白复合聚乳酸(HHK-PLA)骨折内固定棒的生物相容性进行初步观察。
【方法】
1．利用MTS-858 Mini Bionix型生物力学测试机对20根人发角蛋白复合聚乳酸(HHK-PLA)骨折内固定棒进行测试，包括剪切强度和弯曲力，并计算剪切强度、弯曲强度和弯曲模量。
2．36个HHK-PLA试件随机植入18只SD大鼠背部脊旁皮下组织中，分别于术后1、2、4、8、12、16、20、24、28周取出，测量重量损失，了解HHK-PLA在SD大鼠体内的降解情况。扫描电镜(SEM)下观察HHK-PLA试件降解后的结构变化。
3.切取HHK一PLA试件周围的大鼠组织，制作组织切片，观察组织
的炎症反应情况，了解HHK一PLA材料的生物相容性。
【结果】
1.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒具有良好的
初始机械力学强度，其剪切强度为24lMpa，弯曲强度为358MPa，弯曲
模量为13Gpa。
2.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒的体内降解
属性良好，早期降解速度缓慢，而后期降解速度较快。
3.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒植入大鼠体
内1一2周，其周围有明显的纤维组织包裹，结缔组织增生，其间毛细血
管扩张、充血，巨噬细胞、浆细胞、中性粒细胞、成纤维细胞和单核细
胞浸润。8周后HHK一PLA试件周围组织炎症反应逐步减轻。术后12周，
HHK一PLA试件周围组织异物反应基本消失，没有炎症细胞浸润。
【结论】
1.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒具有良好的
初始机械力学强度，能够满足四肢骨的内固定要求。
2.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒的体内降解
属性良好，早期降解速度缓慢，而后期降解速度较快。这种体内降解的
特点有利于骨折愈合，在骨折未愈合时，HHK一PLA基本没有降解，起到
强有力的固定作用，待骨折已经愈合，HHK一PLA开始逐渐降解。
3.人发角蛋白复合聚乳酸(HHK一PLA)骨折内固定棒具有良好的
生物相容性，早期为异物反应，8周后，异物反应逐步减轻，术后12周，
HHK一PLA试件周围组织异物反应基本消失。
Bioabsorbable internal fixation devices have become a focus of many researchers in the past 30 years because of their incomparable advantages to metal materials in orthopaedic operations. However, they can only be used for internal fixation of non weight-bearing bones as their low initial mechanical quality and rapid early period degradation, which originate from their material and technical characteristics. In this study, we summarized foreign and domestic data and produced a new kind of internal fixation rods (HHK-PLA rods), which is made of polyactic acid (PLA) and human hair keratin (HHK). Then, we performed corresponding tests and observation to obtain more evidences for further study and clinical applications. Objective:
1. Mechanical intensity tests were performed on the HHK-PLA rods, including the shearing force and the tri-points bending force, and then shearing strength, bending strength and elastic modulus were calculated.
2. To obtain the data of degradation of the HHK-PLA rods in vivo.
3. To observe the biocompatibility of the HHK-PLA rods. Methods:
1. A material testing machine (MTS 858 Bionix Material Testing System, MTS, Minneapolis, MN) was introduced to test 20 HHK-PLA rods.
2. 36 HHK-PLA rods were randomly transplanted into the hypodermis around the vertebra of 18 SD rats, two rods for each rat, and were taken out 1, 2, 4, 8, 12, 16, 20, 24 and 28 weeks after the operations respectively. And then, weight reduction of each rod was tested to be an indicator of the HHK-PLA rod degradation in vivo. At the same time, the constitution changes of the rods were also observed under the scanning
constitution changes of the rods were also observed under the scanning
electron microscope (SEM). 3. The tissue peripheral to the HHK-PLA rod was cut off and made into
tissue sections to observe the inflammatory reaction, which can indicate
the biocompatibility of the HHK-PLA rod. Results:
1. The HHK-PLA rod processed an outstanding initial mechanical quality, with 241MPa in shearing strength, 358MPa in bending strength and 13GPa in elastic modulus.
2. The degradation procedure of the HHK-PLA rods in vivo was very satisfying as it degraded slowly in the earlier period and went out fast in the anaphase.
3. 1 to 2 weeks after the transplantation, transparent fibrous tissue encapsulation and connective tissue proliferation were seen around the HHK-PLA rods, with the appearance of capillary telangiectasia and hyperemia and macrophage, plasmacyte, neutrophilic granulocyte, fibroblast and monocyte infiltration. The inflammatory reaction died off gradually after 8 weeks and by the end of 12 weeks after the transplantation, there were almost no foreign body reaction and inflammatory cell infiltration seen.
Conclusions:
1. The HHK-PLA rods can fully gratify the demands of internal fixation of limb bones.
2. The characteristic degradation behavior of the HHK-PLA rods was very advantageous to the healing of the fracture because, when in the earlier period, they can produce powerful fixation effects as they degraded little and, while in the anaphase, the rods broke down gradually as the bone itself could already take the place.
3. The HHK-PLA rods presented a satisfying biocompatibility. In the early period, the reaction was foreign body reaction and, after 12 weeks, no abnormality was seen.
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67．李其训，安梅，李春晓，等．人发角蛋白材料人工腱的实验研究与临
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66．邹云雯，王志杰，季爱玉，等．人发角蛋白人工肌腱的免疫学研究及临床应用的初步结果．中华手外科杂志，1999，12(15)：208-211
67．李其训，安梅，李春晓，等．人发角蛋白材料人工腱的实验研究与临
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68． Fabian W, Ruud RM, Fred R, et al. Poly-1-lactide implants for repair of human orbital floor defects. J Oral Maxillofac Surg, 1996, 54: 9-13
69． Hollinger JO, Battistone GC. Biodegradable bone repair materials: synthetic polymers and ceramics. Clin Orthop, 1986, 207: 290-305
70． Majola A, Seppo V, Kimmo V, et al. Absorption, biocompatibility, and fixation properties of polylactic acid in bone tissue. Clin Orthop, 1991, 268: 260-269
71． Seppo S, Yrjo T. K, Tomoyuki S, et al. Immune Response to Polyglycolic acid implants. J Bone Joint Surg, 1990, 72B: 597-600
72． Bostman, H, Makinen, et al. Foreign-body reactions to fracture fixation implants of biodegradable synthetic polymers. J Bone Joint Surg, 1990, 72B: 592-596
73． Buddy D. Ratner BD. Biocompatibility: the Convoluted Path to a Working Definition. Trends in Polymer Science, 1 994; 2(12) : 402-409
74． Adam Curtis, Chris Wilkinson. Topographical Control of Cells. Biomaterials, 1997,28(1) : 1
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76． Ross R. Wound Healing. Sci Am, 1969, 220(6) : 40-50
77． Bostman, Patio, Hirvensalo, et al. Foreign-body reactions to polyglycolide screws. Acta Orthop Scand, 1992, 63: 173-176