第三章 材料與方法
5.3 PLA 對周圍神經再生的影響
PLA 是一種生物可降解性的高分子聚合材料,它無生物毒性,不會 引起嚴重發炎反應,又能以融熔法或配合有機溶劑製成各種形狀,許多 學者均曾嘗試以之為材料製作神經導管[10,11,26,92-95]。但應注意的是,PLA 在水解後會產生乳酸,的確可能會因此而降低封閉環境中的 pH 值,甚 至對神經軸突的再生產生不利的影響。紡絲過程中添加的少量油劑雖然
能避免靜電吸附的干擾,但它會降低PLA 的親水性,使細胞更不易貼附 在材料上。這兩個因素在適當的鹼液精練後都能獲得改善。
根據 Bhang 等[137]在 2007 年所提出的最新報告中指出,將 3:1 的乳 酸 與 羥 基 乙 酸 共 同 聚 合 為 PLGA,其對神經元幹細胞 hippocampal progenitor cells (HiB5) 的 生 存 力 (viability) 與 粒 線 體 代 謝 活 性 (mitochondrial metabolic activity),均遠優於聚左旋乳酸酯(PLLA)與丙交 酯己內酯共聚物(PLCL, lactide and caprolactone 1:1)。而原因據作者推 測,可能是PLGA 親水性較高;而 PLCL 與 PLLA 相對而言較為厭水,
使細胞較不易貼附所導致。
第六章結論
聚乳酸酯與膠原蛋白是近年相當熱門的生物可降解性材料,銀杏葉 酯在適當濃度下也已經被證實對周邊神經有促進再生的效果。在本研究 中,我們跨領域配合紡織編帶的技術,成功研製出一個能協助周邊神經 再生的神經導管,雖然組間的各項分析結果均未達顯著差異,但在動物 實驗中的神經再生成功率各組均達 100%。因此依據製程條件與動物實 驗等部分,大致可歸納出以下幾點結論與建議:
1. 與未經加撚的 PLA 複絲相比,加撚後的 PLA 紗線所製成的導管管 壁,其孔洞的立體結構較為明顯而穩定。
2. 併股會使紗線的直徑增加,以愈粗的股線加撚後再配合編織法製成的 導管,其孔徑也愈大。若參考 2007 年最新的文獻,想製作出孔洞小 於10 µm 的神經導管,或許能嘗試以 75 或 150 丹尼的 PLA 複絲,加 撚後配合較低的芯軸牽引張力,以增加聚合錐的頂角,並進一步縮小 編織物的孔徑。必要時再增加編織的層數,應該能順利製作出理想的 神經導管。
3. 已知鹼液精練能去除聚酯類材料在製作成導管的過程中可能沾附的 油劑或其它灰塵雜質,同時又能增加 PLA 的親水性。根據本實驗中 所測試出的結果,NaOH 濃度在 10-2 M 時,能達到有效清潔卻又不會 對結構造成明顯影響。但若想找出最適合精練的鹼液濃度,或許可嘗 試以不同濃度鹼液精練後,測試 PLA 的水接觸角,以測定其親水性 的改變程度。也可以將精練過的 PLA 與 Schwann cell 共同培養,再 觀察細胞貼附的程度,以找出最適當的鹼液濃度。
4. 在本實驗中觀察到的各組神經再生成功率均為 100%,但在老鼠自殘 的觀察中卻發現一些耐人尋味的現象。雖然未能達到顯著差異,但填 入saline 的對照組不管是自殘的盛行率與嚴重程度,都比其他兩組要 高。這讓我們想到,或許能藉由延長神經缺損的間隙,或縮短犧牲大 鼠的時間,讓神經再生成功率出現不一樣的變化。
5. 由於 Collagen 所產生的物理性交聯可能導致多孔性結構的阻塞,或許
可以考慮減低填入管中的Collagen 的濃度;或是配合不同的細胞外基 質分子,以進一步釐清銀杏葉酯在多孔性導管中,是否能有效促進周 圍神經的再生與成熟。
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