聚二恶烷酮气管支架的动物实验研究阮征;王晋;章晓淼;李毓陵;傅本胜【摘要】目的研究聚二恶烷酮(polydioxanone,PDO)纤维编织的生物可降解气管支架在健康实验兔中的应用可行性和生物降解性.方法应用自制的PDO气管支架,测定其力学性能,并与健康离体的兔颈段气管做比较.通过外科手术将PDO气管支架植入20只健康的实验兔颈段气管;6只实验兔进行除植入支架外的外科手术,作为对照组.植入术后4、8、12周处死实验兔,通过气管镜检查、组织学染色、电镜扫描等观察组织反应及PDO气管支架的生物降解性.结果离体兔颈段气管的径向支撑力157.8 cN,弹性回缩率93.42％;直径6mm的PDO气管支架径向支撑力192.43 cN,弹性回缩率96.8％.20只植入支架的实验兔术后短期内多有食欲下降,1只颈部有皮下气肿,4只出现脓血性鼻分泌物,5只出现间歇性喘鸣音;术后1、2周,各有1只实验兔死于分泌物气道阻塞,尸检发现合并有肺部感染,但支架均完全性膨胀;术后4周,实验兔食欲和活动均正常.术后1个月,气管支架完整,未移位,管腔处于开放状态,有不同程度的分泌物覆盖于气管支架;支气管黏膜上覆盖有气道分泌物和炎症细胞,PDO纤维外表面出现开裂.术后2个月,气管支架轮廓尚可见,有新生组织包裹;支气管黏膜气道分泌物和炎症细胞明显减少,PDO纤维出现溶解和断裂.术后3个月,气管支架形态消失,管腔内有增生的组织;PDO纤维出现完全性吸收,支气管黏膜上可见残留的PDO分解的碎片.未植入支架的对照组实验兔术后无异常表现.结论 PDO气管支架在体外与颈段气管有类似的机械性能,在健康兔气管内具有良好生物可降解性和能够起到扩张支撑的作用.%Objective To study the feasibility and biodegradability of polydioxanone (PDO) tracheal stent in rabbits.Methods The mechanical properties of laboratory-made PDO tracheal stents were measured in vitro and compared with those of tracheas from 6 healthyrabbits.The PDO tracheal stents were surgically implanted into the cervical tracheas of 20 healthy rabbits.The rabbits were euthanized at 4,8,12 weeks after implantation.The biodegradability and tissue response were observed by bronchoscopy,histology and scanning electron microscopy.Six healthy rabbits underwent sham surgery without PDO tracheal implantation as control group.Results The average radial supporting force and elastic restoring rate of the rabbit cervical tracheas in vitro were 157.8 cN and 93.42％,respectively;those of PDO tracheal stents with the diameter of 6 mm were 192.43 cN and 96.8％,respectively.The majority of the 20 experimental rabbits implanted with PDO tracheal stents had decreased appetite in the short term.One rabbits had cervix pneumoderma;4 rabbits had mucopurulent nasal discharge;5 rabbits had intermittent stridor.Two rabbits died of airway obstruction due to secretions at 1 and 2 weeks after surgery,respectively;and autopsy revealed that two rabbits had pulmonary infection with complete expansion of the stents.The appetite and activity of the survival rabbits returned to normal at 4 weeks after operation.The rabbits in the control group showed no abnormal symptoms after operation.Four weeks after operation,the tracheal stents were integrated without displacement,and the lumens were in the open state with different degrees of secretion coverage on the of tracheal stents;bronchial mucosa covered with airway secretions and inflammatory cells,and the PDO fiber was integrated with broken fiber surface.Eight weeks after operation,the tracheal stents were well outlined with new tissue inclusions.The airway secretions of bronchial mucosa and inflammatory cells decreasedsignificantly,and the PDO fiber appeared cracking and partly absorbing.Twelve weeks after operation,the tracheal stents disappeared morphologically,and there was residual and thick tissue in the lumens.The PDO fiber showed completely absorption and residual PDO fragments were found on the bronchial mucosa.Conclusion The biodegradable PDO stent exhibits mechanical strength comparable to that of rabbit cervical trachea in vitro and has good biodegradability,suggesting that it can play the role of expansion and support in healthy rabbit trachea.【期刊名称】《同济大学学报（医学版）》【年(卷),期】2017(038)006【总页数】6页(P27-32)【关键词】气管支架;聚二恶烷酮;生物可降解【作者】阮征;王晋;章晓淼;李毓陵;傅本胜【作者单位】上海交通大学附属第一人民医院胸外科,上海200080;上海交通大学附属第一人民医院胸外科,上海200080;上海交通大学附属第一人民医院胸外科,上海200080;东华大学纺织学院纺织面料技术教育部重点实验室,上海201620;东华大学纺织学院纺织面料技术教育部重点实验室,上海201620【正文语种】中文【中图分类】R655.3气管狭窄，是临床上经常遇到的难题，除手术外，支架植入术是治疗气管狭窄较为理想的方法[1-2]。
常用的有硅酮类和金属类支架，不论是硅酮、还是金属支架，作为一种异物在气管腔内，均可引起气管组织的慢性损伤，造成管壁组织的萎缩、反应性的内膜增生甚至引起周围组织的损伤[1-3]。
生物可降解材料的发展，为解决支架机械性损伤和材料相关性并发症提供了可能。
目前，美国食品药品监督管理局(FDA)批准了数个生物可降解材料，如聚二恶烷酮(polydioxanone， PDO)，聚L-乳酸(poly-L-lactic acid)和聚己内酯(polycaprolactone)，制造医用材料应用于临床。
近年来，也被尝试应用于气管支架的研制[4-6]。
动物实验表明，可降解气管支架，也有适宜的机械性能，同样能够达到维持气道通畅，但有几个问题尚未解决，一是材料相关性并发症未完全避免，如降解产物或其碎片对气道的阻塞；二是气道分泌物较多和黏稠；三是即便是同一种材料，降解的时间有较大的差异。
尽管如此，临床上尝试应用可降解支气管支架也取得了良好的效果，如PDO支架被应用于肺移植后期或生长期儿童的气管狭窄，进一步激发了研究者的兴趣[7-9]。
其最大的优势是能够自行降解，避免再次取出。
PDO材料是生物可降解材料，已经被制作成医用缝线和各类管道(血管支架、胆管支架、胃肠支架等)等应用于临床[10-12]。
先前，利用PDO制作的网状补片，应用于大面积胸壁缺损的动物实验研究，发现术后犬胸壁稳定，呼吸和运动功能良好，伤口愈合良好。
证明其具有足够的机械性能和较长的降解时间，以及良好的生物相容性[13]。
在另一个实验中，应用PDO材料，采用编织技术中的基本纱罗结构成功制造了多种管状支架，具有良好的机械性能、径向支撑力和弹性回缩率[14]。
本研究目的是评估PDO气管支架，与离体兔颈部气管进行力学性能的比较；同时，进行动物实验，将支架植入健康的新西兰大白兔，进行气管镜、电子显微镜扫描等观察，以期望证明具有良好的生物降解性和适用性。
1 材料与方法1.1 PDO支架的组成及机械性能测定支架由直径0.15～0.2mm的PDO单丝纤维，应用基本纱罗结构编织而成，再经过100℃、10min热塑型。