新型介稳定β－钛合金在喉、气管缺损重建中的应用与研究

发布时间：2018-06-20 13:55

本文选题：喉 + 气管　；参考：《第四军医大学》2011年博士论文

【摘要】：各种原因导致的喉、气管缺损是耳鼻咽喉科的常见病与多发病,对于喉气管缺损的修复与重建目前仍无标准的治疗。由于喉气管缺损的原因与严重程度不同给临床治疗带来了极大的困难。多年来研究喉气管缺损的修复与重建以关注假体材料的选择、加工与重建方式为主,近年来一些学者亦通过动物模型研究各种修复材料与长段气管缺损的重建方法,发现假体的血管化与上皮化仍是我们目前临床面临的挑战。然而,新型介稳定β-钛合金材料对于喉、气管缺损的修复与重建目前尚无报道。目的:观察并探讨新型介稳定β-钛合金(TLM)材料在犬的喉、气管缺损修复与重建中的有效性,为喉、气管缺损的治疗提供一种可选择的生物材料,同时为临床治疗提供新的理论依据。方法:1.采用激光切割方法,将钛合金板制成微多孔结构。高压消毒后,置于6孔板中,将小鼠NIH-3T3单细胞悬液按1×105细胞/毫升的密度加入材料表面培养,四小时后取一片材料做扫描电镜观察。测量孔径大小并做图像分析,计算孔隙率。并对材料表面的细胞活力与形态进行观察。 2.取5只犬,将犬的喉与气管充分暴露,切除环状软骨及第1气管软骨环的前1/3形成喉前裂开,将“◇”形的生物材料替代切除的部分喉气管组织,按计划术后3至6个月对受试动物进行气管镜检测。3.采用多孔TLM合金作为10只杂种犬的前喉气管组织再生支架。修复体长度为20mm,修复与重建前环状软骨及第1气管环的缺损,进一步评估TLM合金在该治疗中的有效性。4.取20只杂种犬,随机分成2组:TLM合金组与Ti-2组,每组各10只。切除环状软骨及第1、2气管软骨环,将两种“C”形的管状生物材料替代切除的部分喉气管缺损,按计划术后1、4及12周对受试动物分期进行喉气管镜检查、CT扫描及组织病理学检测。5.选择5只杂种犬行颈部切除5厘米长段气管,将多孔TLM制作成人气管形状以修复环周气管缺损。按计划植入3至8个月后处死动物行内镜检查、CT扫描和病理分析。结果:1. TLM合金表面凹凸不平,呈多孔结构,孔径为70～90μm,孔隙率为32%。细胞表现出有足突和伪足的正常细胞形状。2.术后在所有受试犬中均未见到任何的气道阻塞。未见修复体的移位暴露,内表面无肉芽组织生长及吻合口裂开。3.一只犬于术后一周复查因麻醉意外而死亡;一只犬于术后约一个月因肺部感染而死亡;剩下的8只犬均于术后3至8个月处死;处死时发现所有修复体与周围宿主组织融合。术后内镜检查显示:无1只发生气道狭窄,其中4只长有肉芽组织,一只发现多孔TLM合金板暴露,未观察到吻合口的裂开。然而,所有这些犬均无临床症状。光镜与电镜结果显示:在假体内腔表面有一个正常的粘膜组织生长,及在重建的喉气管内腔位置未观察到任何的可见肉芽组织。4.术后在两组中均未出现吻合口漏。两种材料的修复体均表现出了良好的生物机械强度。组织学检测结果显示:TLM合金修复体周围的成纤维细胞在早期就从网孔长入,且修复体内腔吻合口部位可见有丰富的纤毛柱状上皮,纤毛分布密度也均匀,而在Ti-2组中,修复体周围组织长入较慢,且上皮分布明显不均。5.该假体的机械性能好,假体与周围组织结合紧密,结果充分展示了假体的生物相容性与耐腐蚀性,且没有产生任何的气管狭窄与空气的渗漏,并允许少量的肉芽组织正常长入气管内腔。结论:1.首次采用TLM合金材料应用于喉、气管缺损的修复与重建。TLM合金材料具有良好的生物相容性、耐腐蚀性及机械性能,特别是其弹性模量(30～50Gpa)最接近骨与软骨,为喉气管缺损的重建提供了良好的应力分布。2.首次采用激光切割方法,将钛合金板制成微多直孔结构的喉气管假体,其微孔大小定位在70-90um,孔隙率为30%～35%,厚度为0.5mm。假体植入后发现在早期阶段因周围结缔组织从网孔的长入而保证了气密性,且其微血管的形成为假体腔内的快速上皮化提供了条件,从而最终克服了假体内腔的狭窄。同时发现本重建过程比目前所有试验的其它多孔材料要快。我们进一步证明上皮化结果与气管两端及假体孔隙进入的含丰富毛细血管网的结缔组织有关。3.TLM合金是一种很有潜力的新型喉气管缺损的修复材料,对未来临床的应用具有进一步深入研究的意义与价值。
[Abstract]:The larynx and trachea defect is a common and frequently occurring disease in the Department of Otolaryngology for various reasons. There is still no standard treatment for the repair and reconstruction of the laryngotracheal defect. The reasons for the laryngotracheal defect and the severity of the laryngotracheal defect have brought great difficulties to the clinical treatment. The selection of body materials, processing and reconstruction are the main methods. In recent years, some scholars have also studied the reconstruction methods of various repair materials and long segment trachea defects through animal models. It is found that the vascularization and epithelialization of the prosthesis are still the challenges we face. However, the new metastable beta titanium alloy has been used to repair the larynx and the trachea defect. There is no report on the reconstruction.
Objective: To observe and investigate the effectiveness of a new mediate stable beta titanium alloy (TLM) in the repair and reconstruction of laryngeal and tracheal defects in dogs, and to provide a choice of biomaterials for the treatment of laryngeal and tracheal defects, and provide a new theoretical basis for clinical treatment.
Methods: 1. the titanium alloy plate was made into micro porous structure by laser cutting. After high pressure disinfection, it was placed in the 6 hole plate. The mouse NIH-3T3 single cell suspension was cultured on the surface of the material with the density of 1 x 105 cell per milliliter. After four hours, a piece of material was taken for scanning electron microscope. The pore size was measured and the porosity was calculated. The porosity was calculated and the porosity was calculated. The cell viability and morphology were observed on the surface of the material.
2. in 5 dogs, the dogs were fully exposed to the larynx and trachea, the cricoid cartilage and the anterior 1/3 of the 1 tracheal cartilaginous ring were removed to form the anterior larynx. The tracheal tissue of the resected part of the laryngoscope was replaced by the biomaterial of the shape of the larynx. The tracheal microscopic examination of the subjects was performed for 3 to 6 months after the planned operation and the porous TLM alloy was used as the anterior larynx of the 10 hybrid dogs. Endotracheal tissue regeneration. Repair body length was 20mm, repair and reconstruction of cricoid cartilage and 1 tracheal ring defects, further evaluate the effectiveness of TLM alloy in the treatment of.4. to take 20 hybrid dogs, randomly divided into 2 groups: TLM alloy group and Ti-2 group, 10 in each group. Excision of cricoid cartilage and 1,2 tracheal cartilage ring, two "C" shaped tubes The resected partial laryngotracheal defects were replaced by biomaterials, and laryngotrachoscopy was performed at 1,4 and 12 weeks after the planned operation. CT scanning and histopathological detection of.5. selected 5 hybrid dogs with 5 cm long trachea excised in the neck. The porous TLM was made to repair the tracheal defect of the circumferential trachea. 3 to 8 were implanted as planned. After a month, the animals were sacrificed for endoscopy, CT scan and pathological analysis.
Results: the surface of 1. TLM alloy was uneven and porous structure, the pore size was 70~90 mu m, and the porosity was 32%. cells showing the normal cell shape of the foot process and the puppet foot. No airway obstruction was seen in all the dogs after the operation. No transfer exposure of the repair body, the inner surface without granulation tissue growth and the anastomotic opening of.3. a dog were not seen. A dog died a week after an anaesthesia; one dog died about one month after the operation due to lung infection; the remaining 8 dogs were killed 3 to 8 months after the operation; all the prostheses were found to be fused with the surrounding host tissues at the time of death. The postoperative endoscopy showed that there were no 1 strictures, 4 of them had granulation tissue, and one found The perforated TLM alloy plate was exposed and no anastomotic cleavage was observed. However, all of these dogs had no clinical symptoms. The results of light and electron microscopy showed that there was a normal tissue growth on the surface of the prosthesis, and no visible anastomosis in the two groups was not observed in any of the visible granulation tissue.4. in the rebuilt laryngotracheal cavity. The prosthesis of the two materials showed good mechanical strength. The histological examination showed that the fibroblasts around the TLM alloy prosthesis grew from the mesh in the early stage, and the plentiful ciliated columnar epithelium was seen in the anastomotic site of the repair body, and the density of the cilia was evenly distributed in the Ti-2 group. The mechanical performance of the prosthesis is good and the prosthesis is closely associated with the surrounding tissue. The result fully demonstrates the biocompatibility and corrosion resistance of the prosthesis, and does not produce any tracheal stenosis and air leakage, and allows a small amount of granulation tissue to grow normally into the endotracheal cavity.
Conclusion: 1. TLM alloy materials were used for the first time in the larynx. The repair and reconstruction of the defect of the trachea has good biocompatibility, corrosion resistance and mechanical properties, especially its modulus of elasticity (30 ~ 50Gpa) is closest to the bone and cartilage, which provides a good stress distribution for the reconstruction of laryngeal and tracheal defects,.2. is the first time to use laser cutting side. The titanium alloy plate is made into a laryngotracheal prosthesis with microporous structure of the titanium alloy plate. The micropore size is located at 70-90um, the porosity is 30% to 35%, and the thickness is 0.5mm. implant. It is found that the air tightness is ensured by the growth of the surrounding connective tissue from the mesh in the early stage, and the formation of the microvessel provides a strip for rapid epithelial cells in the false body cavity. It finally overcomes the stenosis of the inner cavity of the prosthesis. It is also found that the reconstruction process is faster than all the other porous materials currently tested. We further demonstrate that the results of the epithelialization are a potential new type of laryngotracheal deficiency associated with.3.TLM gold in the connective tissue with the rich capillary network at both ends of the trachea and the pores. The damaged repair materials will have further significance and value for future clinical application.
【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R762

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