【作者】 王胜军；

【导师】 迟放鲁；

【作者基本信息】 复旦大学 ， 耳鼻咽喉科学， 2005， 博士

【摘要】 由于先天畸形、外伤等因素造成的耳廓缺失的全耳廓再造手术是最具挑战性的整形手术之一,全耳廓再造的外形在很大程度上取决于支架材料的使用。自体软骨易于雕刻成形,不存在排斥反应,并发症较少,在临床应用广泛。它的不足之处在与取材增加手术创伤,有并发气胸和胸骨畸形的可能性。迄今已有很多材料代替自体软骨作为全耳廓再造的支架,各种材料均有利弊。 镍钛形状记忆合金作为一种生物材料被广泛应用于医学领域。本实验即探索应用镍钛记忆合金丝网作为耳再造支架进行全耳廓再造的可能性。新西兰大白兔12只分成皮肤扩张组和未扩张组,扩张组先行皮肤扩张后再植入已制成人耳廓形状的镍钛合金丝网作为全耳廓再造的支架,未扩张组则直接皮下植入支架。观察支架植入后不同时间点（1、3、6、9、12月）的机体反应,包括HE染色、免疫组化（VEGF、CD31）、扫描电镜检查;利用放射性核素^99mTc-PYP动态观察手术后1、3、6、9、12个月的支架植入处与相对应部位局部新生血管增加血供的变化情况。将支架植入家猪皮下,术后观察不同时间血常规及肝肾功能变化情况,以及用能谱分析法测定植入前后毛发中镍钛微量元素的含量变化。 扩张组皮肤扩张顺利,未出现血肿、感染、血运障碍、扩张困难、渗漏、切口裂开、扩张器外露等并发症;支架植入后局部皮肤出现水肿,术后3周内水肿开始消退,皮肤脱屑,局部皮肤基本恢复正常。未扩张组则植入后局部反应较轻。连续观察12个月扩张组5例局部生长良好,植入支架位置未移位,两侧皮肤粘连紧密,局部无感染、排斥表现,支架无外露,再造耳廓形态较满意,能表现耳廓的精细结构。1例于12月时出现支架外露,再次修补成功。未扩张组未发生支架外露,但外形表现较扩张组差。支架植入后1、3个月时周围形成的纤维包膜主要由成纤维细胞构成,新生血管增生明显;6个月时表现出胶原增生,囊壁逐渐胶原化,由厚变薄,9、12个月时则胶原和血管趋于稳定,由纤维细胞构成囊壁。支架植入周围组织表达VEGF阳性细胞数量逐渐增多,扩张组要多于未扩张组,在3个月时变化最显著。以CD31标记的微血管密度在术后3月内显著增高,6个月后无显著性差异。扩张组总体CD31标记的新生血管计数MVD与VEGF表达的阳性细胞数之间呈明显正相关（r=0.772,p<0.01）。扫描电镜检查显示植入支架金属表面光滑,无金属腐蚀;周围组织细胞结构正常,增生的胶原纤维和网状纤维显示清晰。^99mTc-PYP放射性核素显像显示术后1、3、6个月时表现为植入处单位像素的放射性计数要高于对侧相对应部位,在3月时表现得最明显,9、12月时则无明显差别。更多还原

【Abstract】 Microtia, a smaller than normal and usually malformed auricle, affects about one in every 7000 to 8000 infants in the general population, occurring more often in right ears and males. The auricle is one of the most complex three-dimensional structures of the external body. The delicate structure of the auricle is defined by the convolutions of the underlying cartilaginous framework. Reconstruction of a congenitally absent ear is a great challenging task to the plastic surgeon. Factors contributing to this challenge include the thin skin and delicate framework. To restore an ear that looks like an ear, familiarity with the anatomical components of the normal auricle is imperative. Most ear reconstructive techniques have been derived from the formula that uses a framework placed beneath the skin to create an ear form.Numerous materials have been used to fabricate the ear framework, but autogenous costal cartilage is the most reliable and commonly used material for ear reconstruction of the framework, and has been proved to be the standard material. It has a demonstrated track record for durability and stability over time but is not without shortcomings. The complications evoked by costal cartilage harvest include the immediateproblems of the considerable pain and discomfort, even pneumothorax, and the delayed issues of chest wall deformity and scarring. Long-term complications in the reconstructed ear primarily relate to resorption of the cartilage framework, which may alter the shape and form of the auricular components.The use of an alloplastic auricular framework to reconstruct the microtic ear has been advocated to provide a more consistent aesthetic result and to avoid rib cartilage donor site morbidity. By using an alloplastic framework, reconstruction may begin at an earlier age because the size of the child’s rib cartilage is not necessary.The initial aesthetic results of Silastic framework for auricular reconstruction were often excellent, and without donor-site deformity. However, long-term follow-up demonstrated spontaneous exposure of the implant with failure of the reconstruction in many cases. The use of silicone implants for ear reconstruction were abandoned.The use of porous polyethylene has been recently advocated by Reinisch. Porous polyethylene causes minimal tissue reaction, and its porous quality allows soft-tissue ingrowth, thereby providing greater stability. With technique modification, the performance of these constructs with good results were reported, but this technique remains to be proved safe and reliable.The potential to fabricate autologous parts has recently become ablooming field of scientific endeavor. Proponents for creating complex parts initially sought to render three-dimensional form through the process of molding tissue. Unfortunately, the constructs did not maintain their engineered shape over time because of the lack of a stable substructure. Although promising, microtia reconstruction using a tissue-engineered, prefabricated framework is not yet a practical option.Biomedical applications of Ni-Ti shape memory alloys have been extremely successful because of the functional properties of these alloys, increasing both the possibility and the performance of minimally invasive surgeries. The biocompatibility of these alloys is one of the important points related to their biomedical applications as orthopedic implants , cardiovascular devices , and surgical instruments.The aim of this study was to explore the possibility of nickel-titanium (NiTi) shape memory alloy stent in ear reconstruction in vivo. With this goal, two discrete experimental groups were formed, each comprising 6 New Zealand rabbits. Each animal underwent subcutaneous implantation with a NiTi alloy framework like human auricle under general anesthesia. In 6 animals, the implant was encased after skin expansion; in the other 6, it was directly placed. Implant vascularization was evaluated at months 1, 3, 6, 9,and 12 for histological analysis. The immunohistochemical methods were used to examine expression of VEGF and CD31 in tissue around the implant at 1,3,6,9 and 12 month after implantation,respectively. The NiTi alloy implant was examined microscopically with scanning electron microscopy. The fibrovascular ingrowth rate of implants is determined by bone scanning using 99mTc-PYP 1,3,6,9,12 months after implantation. The analysis of aspects related to the biocompatibility of the NiTi alloy framework is performed by assessing each of their elements in pig’s hair, nickel and titanium, separately.One rabbit had exposure of the NiTi alloy framework due to overlying skin flap necrosis, but can be repaired with animal skin without the complete removal of the framework. All the other rabbits tolerated the implant well, and there were no complications. On histopathologic examination, fibrovascularization gradually increased over time. The implant harvested at 1 months showed only partial vascularization, and were completely vascularized at 3 months. The amount of VEGF-positive cells was markedly increased in 6 months and reached the highest at 3 month in the tissue. Compared with the other months , the CD31 positive endothelial cells at 3 month were significantly different. The over-expression of VEGF had a positive correlation of with the higher microvessel density(MVD) count.The results demonstrated that the fibrovascular ingrowth rate of implant assessed by 99mTc-PYP bone scan using ratios of 99mTc-PYP activity in placement regions is more high than the contralateral normal region.更多还原