新型可降解人工泪小管的制备与表征

PREPARATION AND CHARACTERIZATION OF NOVEL DEGRADABLE ARTIFICIAL LACRIMAL CANALICULUS

目的研制一种可生物降解的胶原-壳聚糖-聚乙烯醇[poly(vinyl alcohol),PVA]复合人工泪小管,用于治疗因泪道阻塞导致的溢泪症。方法按照一定比例均匀混合胶原、壳聚糖、医用PVA溶液,通过反复的冻融过程使其形成弹性凝胶,再依次经过清洗、造孔、脱水、剪切后即得T1、T2和T3组的可降解人工泪小管。光镜下观察表面形貌和测量内、外直径。扫描电镜观察T2组人工泪小管凝胶态和干态的断口形貌,以及是否存在相分离现象。通过吸水溶胀性能测试计算3组人工泪小管的吸水率和膨胀率。采用体外降解实验初步观察3组人工泪小管的降解情况。结果通过物理交联成胶的方法成功制备出内径0.5～0.7mm,外径0.9～1.5mm,长度≥20mm的胶原-壳聚糖-PVA复合人工泪小管。扫描电镜观察到液氮脆断的人工泪小管内部成分分布均匀,内外壁表面平整,冷冻干燥的人工泪小管断口呈凝胶态的互穿网络结构。3组不同成分的人工泪小管在PBS溶液中浸泡30min后均快速吸水溶胀,外径扩大100%～120%,内径扩大20%～30%,并且随胶原含量增高,溶胀速度增快,平衡溶胀率增大。3组人工泪小管在37℃含2mg/mL溶菌酶的PBS液中浸泡1个月后,表面有部分细小絮状物,管口开裂,管壁变薄,透明度增加。在70℃PBS溶液中加速降解2d后,该小管成白色糊状。结论制备的新型可降解人工泪小管具有良好的力学性能和吸水溶胀性,便于手术操作,可支撑泪道,利于泪液的流通,防止泪小管粘连,有望成为一种治疗泪道阻塞的新材料。

Objective To develop a novel biodegradable collagen-chitosan-[poly（vinyl alcohol）, PVA] composite artificial lacrimal canaliculus for treating tear overflowing （epiphora） caused by canalicular obstruction. Methods Homogeneously mixing solution composed of collagen, chitosan and PVA with different ratios was prepared. After several cycles of freezing/thawing process, the mixing solution was transferred into elastic hydrogel. Then the hydrogel was rinsed, punctured, dehydrated and trimmed, and three groups （T1, T2 and T3） of novel artificial lacrimal canaliculus were obtained. The appearance and diameter of all samples were observed under optical microscopy. The cross-section before and after drying as well as phase distribution of sample T2 was observed by SEM. The water absorption ratio and expanding ratio in PBS solution were calculated from three swelling behavior curves. The degradability of groups T1, T2 and T3 were preliminary analyzed by degradation experiment in vitro. Results The micro-tubes with 0.5-0.7 mm in inner diameter, 0.9-1.5 mm in outer diameter and more than 20 mm in length were fabricated successfully through physical crosslinking without addition of toxic cross-linker. SEM result showed that the sample had uniform phase distribution and smooth surface at dried state as well as interpenetrate network structure at hydrogel state. It was seen from the swelling behavior curves that groups T1, T2 and T3 swelled rapidly within 10-30 minutes, and formed elastic composite hydrogel pipes. In addition, the expanding ratio of inner and outer diameter of the tube was 20%-30% and 100%-120% with swelling, respectively. The equilibrium water content of the hydrogel pipes increased with increase of collagen composition. Three groups of samples were immerged in PBS solution contained 2 mg/mL lysozyme at 37℃ for 1 month, their nozzle cracked, their wall became thin and more transparent. And also, there was small floc deposited on the tube surface. The samples were degraded into mash after they were soaked in PBS solution at 70℃ for 2 days. Conclusion The novel artificial lacrimal canaliculus with good mechanical property and high water absorption is in favor of operation, tear passing and anti-conglutination. It will be a potential candidate for treating the lacrimal passage occlusion.