摘要
研究背景
气管病变，无论是恶性肿瘤还是良性狭窄，其理想的治疗方法是切除病变段气管一期对端吻合。在人类，当环形切除气管超过50mm-60mm时，就无法通过解剖分离的方法来作端端吻合，必须植入气管替代物才能重建气管的连续性以维持气道的通畅。气管替代物主要包括同种异体气管、自体组织、人工气管假体和组织工程化气管。同种异体气管移植(tracheal allotransplantation)存在着血供障碍和免疫排斥，自体组织(autogenous tissue)由于其与气管解剖结构的显著差异，加上数量有限以及供应区的缺损限制了其在气管重建领域中的应用，组织工程化气管(tissue-engineered trachea)的研究国际上尚处于起步阶段，还有大量的技术难题需要解决。人工气管假体(tracheal prosthesis)的研制始终是气管重建外科最为活跃，最为前沿的研究领域。
高分子材料科学和生命科学的完美结合，是20世纪后叶世界科学技术交叉渗透与发展的重要产物，为人类组织器官的修复和改善病损组织的功能提供了必要的替代材料，也为临床医学的发展开辟了新的途径，注入了新的活力。高分子生物材料(polymeric biomaterials)中聚合物具有一定的机械强度和加工性能，可为细胞生长和组织再生提供适宜的支架，而生物活性材料(bioactive materials)由于具有良好的生物相容性和可降解性，对组织结构的再生和修复起着重要的诱导和促进作用。如果能将此两类不同特性的材料进行有机组合从而产生综合两者优异性能的复合体，不仅是理论方面的创新，同时也是技术上的创新，将为研制结构和性质类似于人体的人工气管开辟更为广阔的途径。
研究目的
一、研究生物材料的生物学特性和理化性能进行人工气管各组分材料的筛选和优化组合；
二、按照医疗器械生物学评价标准，研究所选生物材料的生物相容性和安全性，并对其进行综合评价；
三、通过材料的复合成型工艺及编织工艺制备在理化性能和生物力学特性方面与宿主气管相匹配的人工气管，研究生物材料人工气管的生物力学性能；
四、通过构建犬颈段气管缺损与重建实验动物模型，动态观察术后人工气管的移植状况以及其周围组织结构的功能改变。
第二二月只医大学博创匕学亡之示仑文中j忆摘委胸产绍外月斗学专J七
对究内容与方法
一、生物材料人工气管的设计与选材
筛选出具有良好强度和弹性的生物材料编织制成网管构成基本支架，网管内壁采
用涂层技术进行封闭，再筛选出具有良好细胞亲和性，有助于组织再生和修复的生物
活性材料覆盖于网管外壁。分别通过拉伸试验对支架材料聚丙烯、聚乙丙交酷以及动
态热力学试验对涂层材料聚氨酷的力学性能进行测定;通过将胶原蛋白、轻基磷灰石
复合制成外覆层材料，对其理化性质和结构进行分析。
二、生物材料人工气管组分材料的生物学评价
按照医疗器械生物学评价15010993一1:1992和GB/T16886.l一1997标准和要求，我
们对生物材料人工气管各组分材料进行了体内外生物相容性和安全性试验研究，包括
细胞毒性试验、急性全身毒性试验、溶血试验、热源试验、皮肤致敏试验、遗传毒性
试验和体内降解试验，旨在对该材料进行有效的细胞毒理学分析、生物相容性评价和
降解性能评定。
三、生物材料人工气管的制备及其生物力学性能测定
采用特制的小口径针织圆纬机直接编织出网管状结构，经过涂层、放电、浇注、
冷冻干燥和真空热交联等一系列工艺措施制备出复合型生物材料人工气管，并对其纵
向拉伸性能和径向支撑性能进行了测定。
四、犬颈段气管缺损与重建实验动物模型的构建
通过使用生物材料人工气管构建犬颈段气管缺损与重建动物模型，动态观察术后人
工气管的移植状况以及其周围组织结构的功能变化，为进一步完善人工气管的设计与
制备提供有价值的实验依据和技术可行性。
拼究任果
一、聚丙烯单丝质地柔韧，光滑而有弹性，断裂负荷24.scN/dtex，延伸率达36
%，聚乙丙交酷复丝为可控降解纤维，质地柔软，断裂负荷3.85cN/dtex，延伸率达
22.5%，两者均具有良好的可编织性能和加工成型性能;聚氨酷具有较高的弹性模量
和强度，属高品质涂层材料;胶原蛋白/轻基磷灰石微孔状海绵孔径100林m一150拼m，为
细胞的粘附、迁移和再生提供了适宜的三维空间。
二、人工气管各组分材料无细胞毒性，对细胞形态、生长代谢和增殖不构成损害，
无致敏反应和热源作用，无潜在的遗传毒性，材料浸提液不引起溶血反应和全身急性
毒性反应;胶原蛋白/经基磷灰石和聚乙丙交酷材料植入体内未见组织变性、坏死或异
军二J比医岁冤学t.d匕学七立亏仑文中文摘要胸川‘外科学专习匕
常增生现象，材料基本降解吸收，最终被新生的纤维组织所替代。
三、采用小口径针织圆纬机实现了人工气管的整体编织。内壁光滑有利于气道通
畅，外壁绒毛状且可降解吸收。经过涂层、放电、浇注、冷冻干燥和真空热交联等一
系列工艺制备出复合型人工气管，对其纵向拉伸性能和径向支撑性能进行了测定。其
结构包括:(1)以聚丙烯、聚乙丙交酷缝合线通过编织形?
Background
Stenosis,complete obstruction or tracheal defects may occur due to trauma,tumors, granulomatous disease,and long-term endotracheal intubation. Since the first tracheal resection and re-anastomosis was performed on humans in 1884,various surgical methods and techniques for tracheal reconstruction have been developed based on the degree and the cause of the tracheal diseases.Primary end-to-end anastomosis is preferred in the reconstruction of tracheal defects less than 50mm-60mm in humans. A large variety of allografts, prosthesis,autogenous tissue and tissue-engineered trachea have been extensively tried to repair larger,circumferential tracheal defects,but only limited success have been achieved experimentally and clinically.Graft ischemia and immunorejection have hindered the success of tracheal all ografts. Reconstruction with autogenous tissue have been found unsatisfactory due to inadequate airway function and poor sources. The research of the tissue-engineered trachea is still in initial stages,and remains numerous problems to be tackled.The development of the prosthetic tracheal grafts was,is and will be a challenging issue in tracheal surgery.
In recent years, the perfect integration and development of polymeric sciences and life sciences provide necessary substitutes for restoring and improving the functions of the impaired tissues and oragens.Polymeric biomaterials comprise mainly synthetic and natural materials.The former such as polymers are characteristic of certain mechanical strengths and processing properties,which can provide appropriate scaffolds for cell growth and tissue regeneration.Compared with the former, the latter possessing excellent biocompatibility and biodegradability play a crucial role in inducing and facilitating cell growth and tissue regeneration. If the two kinds of different materials above could be integrated properly,it would be a great innovation theoretically and technically in designing and prefabricating tracheal prosthesis.
Objective
1. Screening and integrating perfectly the appropriate materials for the design and prefabrication of tracheal prosthesis.
2. Evaluating comprehensively the biocompatibility and biological reliability of the selected materials in vitro & in vivo in accordance with ISO and GB/T of China.
3.Prefabricating the tracheal prosthesis matching with the host physicochemically and biomechanically by the techniques of synthesizing and knitting;Measuring the bio-mechanical properties of the newly developed tracheal prosthesis.
4.Establishing the animal model of the tracheal defects and reconstruction,and observing dynamically the situation of the implanted tracheal prosthesis and the functional changes of tissue structures surrounding the prosthesis.
Methods
1.Screening the appropriate biomaterials prepared for developing the tracheal prothesis. Biomaterials possessing excellent strength and elasticity were selected to prefabricate the mesh tube as a scaffold,whose inner lumen were coated by polymers and the exterior were laminated by bioactive materials.The biomechanical properties of
polypropylene(PP), poly(lactic-co-glycolic acid)(PGLA) and Polyurethane(PU) were measured systematically by the use of the elongation test.dynamical thermadynamics, respectively.The structure of Collagen(Col)/Hydroxyapatite (HA) composites was analysed by scanning electron microscope(SEM).
2.Evaluating comprehensively the biocompatibility and biological reliability of the selected materials in vitro & in vivo. The biocompatibility and biological reliability of the selected materials were evaluated comprehensively in accordance with ISO10993-1:1992 and GB/T16886.1-1997. The in vitro cytotoxicity test,acute systemic toxicity test ,hemolysis test,pyrogen test, skin hypersusceptibility test, genetic toxicity test and in vivo biodegra-dation test were all conducted.
3.Prefabricating the tracheal prosthesis and measuring its biomechanical properties. A tubular mesh were developed by the specific micro-calibre kintting-machine,
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