聚二恶烷酮气管支架的动物实验研究

Feasibility and biodegradability of polydioxanone tracheal stent in rabbits

关键词:  气管支架  聚二恶烷酮  生物可降解

Key words:  tracheal stent  polydioxanone  biodegradability

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157.8cN,弹性回缩率93.42%；直径6mm的PDO气管支架径向支撑力192.43cN,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。

Abstract:

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 healthy rabbits. 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 157.8cN and 93.42%, respectively; those of PDO tracheal stents with the diameter of 6mm were 192.43cN 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 decreased significantly, 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.