評估聚乙烯醇/右旋醣酐/甲殼素水凝膠在傷口敷料之應用

Abstract

傷口的產生，代表組織遭受連續性的破壞，並需要依照傷口的深淺、位置、面積以及病人的生理狀態，採取適當之處理方式以達到最佳的治癒效果。傷口癒合的發炎期和細胞增生期間，由於作為物理性屏障之表皮受到破壞，許多外界的因子和傷口本身的狀態，都會影響傷口癒合的快慢、發炎期的長短以及最終留下疤痕與否。 而傷口敷料的使用，則可以降低諸如傷口感染、缺乏水分和滲液過多等問題造成之傷害。傳統使用的乾式敷料，諸如紗布與棉花，雖然能夠有效阻隔外界的機械傷害，卻沒辦法維持一個適合體液流通的理想環境，使免疫細胞交流、皮膚細胞進行新生。更因為容易沾黏、更換不易而造成使用上的困難，進一步的增加復原的時間和留下疤痕的機會。 相較於乾式敷料，濕式敷料的問世時間較短。從六零年代開始，世人才發現當傷口處於濕潤的狀態下，會癒合得較為快速，留下疤痕的機率也顯著降低。除了可以讓患部血管新生速度增快，濕式敷料更具有保濕、不易沾黏、易更換、可大面積使用等優點。常見的濕式敷料包括膠原蛋白(collagen)、褐藻酸 (alginate)、聚氨酯泡棉 (polyurethane foam) 和水凝膠 (hydrogel)。 水凝膠是一種具有立體結構的物質，可以在結構穩定的狀態下吸收大量的水分，物理性和化學性的交聯都可以維持其立體狀態。大自然中的膠原蛋白、幾丁質 (chitin)、褐藻酸和瓊脂醣 (agarose) 都可形成水凝膠。近幾年來，水凝膠因為具有良好的敷材特性，更可進行藥物釋放，故被廣泛地運用在傷口敷材上。本篇研究將會利用三種高生物可相容性的物質，研發出理想之傷口敷料。分別為具有高保水性的聚乙烯醇 (poly (vinyl alcohol))、可促進傷口癒合的右旋醣酐 (dextran)以及具有抗菌效果的甲殼素 (chitosan)，並利用以戊二醛 (glutaraldehyde，GA) 進行交聯。 首先，考量日後敷料製成與使用的方便性，選擇6% 的PVA製作水凝膠來進行後續實驗。抗菌的效果為影響傷口感染與否的決定因素，運用接觸型抗菌實驗，發現0.25% chitosan之添加組別具有最佳之抗菌效果。透過細胞毒性實驗，確定水膠製程中並不會有過量GA之殘留，造成對細胞的傷害；另一方面，細胞增生實驗的結果也顯示出4% dextran可以提升細胞初期的附著。在後續的材料特性分析中，更發現chitosan和dextran的添加，可以增進水凝膠的熱穩定度、機械性質、水分含量和保水程度。故未來發展成水凝膠敷材時，將可達到促進傷口癒合的效果。

As the wounds appear, it means that the skin is under continuous destruction. The best treatments should be adjusted according to the depth, location, size and the medical conditions of the wounds. In the period of inflammation and cell-proliferation, the efficiency of recovery, duration of the inflammation, and the final fate of the scars are determined mainly by various external factors and the condition of the wounds. Applications of wound-dressings could prevent further impairments, such as pathogen infection, dehydration and excessive exudate. Traditional dry wound dressings, like cotton and gauze, have the ability to block external mechanical invasions, but could not provide an ideal environment for communication of leukocytes within the liquid and proliferation of epidermal cells. Furthermore, since dry wound dressings are easily adhesive to the wounds, it causes difficulty in changing and increases the duration of recovery and the potentials of permanent scars. Moisture-retentive dressings have not been used for a very long time. In the 60’s, it was discovered that the period of recovery and possibility of permanent scar significantly reduced when the wound was in a moist environment. The moisture-retentive dressings not only elevate the cell proliferation rate, but also have many advantages, such as moisturizing and non-sticky texture, less difficulty in changing, and flexible dressing-size. Collagen, alginate, polyurethane foam, and hydrogel, are commonly used as moisture-retentive dressings. Hydrogel is a three-dimensional structure with hydrophilic polymer chain, having the ability in absorbing water in great amount. Either physical or chemical cross-links could contribute to its three-dimensional structure. Naturally-occured collagen, chitin alginate and agarose could form hydrogel. Due to its splendid characters, hydrogel could be used in not only wound-dressings but also drug-delivers. Three components with high bio-capability are integrated to produce ideal wound-dressing. These components are poly (vinyl alcohol) with high water-content, dextran with the ability in promoting wound-recovery and chitosan with anti-microbial characteristic, when glutaraldehyde is used as the cross-linker. In this study, 6% PVA hydrogel was chosen owing to its texture and further applications. In the anti-microbial test, 0.25% chitosan was found to provide the best anti-microbial ability. In the cell-toxicity test, it has shown that no residue of glutaraldehyde, which might undermine the growth of cells, was remained in our hydrogel-making procedure. In the cell-proliferation test, the greatest cell-proliferation happened to be on the hydrogel with 4% dextran. In the following physical analyses, the addition of chitosan and dextran was appeared to promote the thermo-stability, mechanical properties, water retention and moisturizing ability in the PVA hydrogel. In conclusion, the PVA/chitosan/dextran hydrogel has a promising potential as a wound dressing in the future.