以鄰苯二酚接枝褐藻酸鈉水膠減少肺漏氣之效果

Abstract

肺臟切除術是針對肺臟腫瘤、肺囊腫或是感染性疾病所使用的治療方式，切除後的肺葉或氣管會以自動吻合器進行術後釘合。諸多併發症中，以肺臟持續性漏氣最為常見，可能引發肺部感染、膿胸或是引流時間延長等問題。為減少漏氣現象，現今會使用組織膠或支撐材來補強釘腳孔隙或是癒合不完全形成的傷口。然而，這些商品價格普遍昂貴，且部分具細胞毒性或黏性不足等問題。因此我們合成出一種新材料，希望能降低以上情況並達到減少肺漏氣的效果。材料的設計引自仿生的概念，以褐藻酸鈉做為基底合成一種可注射式水膠，作為新的組織膠。近年研究發現，貽貝類的觸手可於含水環境中有效黏著於有機與無機物表面，原因來自於其成分中大量的鄰苯二酚（catechol）。這種官能基能與不同表面鍵結產生共價鍵及非共價鍵，提供高度的黏性。因此，我們透過EDC/NHS反應將多巴胺（dopamine），接枝在高分子褐藻酸鈉上，形成鄰苯二酚-褐藻酸鈉（catechol-alginate）。將此材料溶成水溶液，與不同濃度高碘酸鈉混和，使之於短時間內形成高黏著性的水膠。透過成膠時間、組織拉伸、爆破壓力、機械性質以及細胞活性等測試，確認我們合成的材料，確實可有效在肺部傷口外形成保護層，並且不具明顯細胞毒性。以現階段實驗結果發現，以2%鄰苯二酚-褐藻酸鈉，與高碘酸鈉離子對鄰苯二酚莫爾數比為0.75的高碘酸鈉溶液形成之水膠，能提供組織最佳的黏著力，並且負荷285.7 ± 36.0 mmH2O的肺部壓力。

Prolonged air leak is one of the most common complications after lung parenchyma resection. To deal with the problem, surgeons might use tissue adhesives or buttressing material to wrap around the anastomosis of lung incision after stapling. However, the commercial bioadhesives have drawbacks such as low adhesive properties and cytotoxicity. Hence, we conceived an idea of using mussel protein-based material to make a potential bioadhesive since mussel exhibits strong bulk wet tissue adhesion due to the function of abundant catechol groups in their byssus. In this paper, we conjugated dopamine, a small molecule with catechol group, onto the backbone of sodium alginate to produce catechol-alginate; and then successfully fabricated adhesive hydrogel in the presence of sodium periodate (NaIO4). To investigate the effect of this adhesive, several methods were used –vial tilting assay, cell viability assay, mechanical properties, lap shear stress test and ex vivo test of bursting pressure. Based on the results, 2% C-Alg and NaIO4 with IO4/catechol ratio 0.75 was found as optimum, having the best adhesive properties and enabling a bursting pressure of rat lung to 285.7 ± 36.0 mmH2O.