利用共溶劑系統與相轉化法製作多種可降解高分子奈米結構薄膜與三維支架

Abstract

細胞外基質(extracelluar matrix, ECM)，在細胞的貼附、增生、遷移和分化皆扮演了重要的腳色，而模仿細胞外基質結構的材料被認為是更有利於組織工程的應用。在本研究中，發展多種的共溶劑系統去調製出熱力學介穩態的高分子溶液，在利用濕式相轉化法或熱誘導式相轉化法結合濕式相轉化法來製作出奈米結構的薄膜，再藉由粒子瀝濾法(particle-leaching method)製造出180-250 um(使用100-300 um的糖顆粒為致孔劑)孔洞與整體為奈米結構的仿生支架(ECM-liked scaffold)。此高分子共溶劑系統具有多變化性，其高分子可由聚乳酸(polylactide)、聚己內酯(Polycaprolactone)、可降解聚酯型聚胺酯(biodegradable poly(ester)urethane)所替換，其中的相對非良溶劑(relatively poor solvent)可由N,N-二甲基乙酰胺(N,N-dimethylacetamide)、四氫呋喃(tetrahydrofuran)、二甲基亞碸(dimethyl sulfoxide)、二甲基甲醯胺(dimethylformamide)與丙酮(acetone)所替換；且此共溶劑系統的高分子溶液在25oC的保存性高(5個月結膠)，再配合容易控制的加工製程，所以具有高度再現性，未來預期能將此具有大孔與整體奈米結構的三維支架，應用於各種組織工程的範疇當中；經由大氣電漿改質將聚乳酸奈米纖維薄膜接枝幾丁聚醣與磺酸化幾丁聚醣，可使薄膜的抗菌性與親水性大幅提升。

Extracellular matrix (ECM) plays an important role in cell attachment, growth, migration, and differentiation. Biofunctional materials that mimic the ECM are considered more favorable in tissue engineering. In this study, a various polymer co-solvent system was developed to configure thermodynamically metastable polymer solution. The nanostructured membranes were fabricated via wet-phase separation or a combination with thermal-induced phase separation (TIPS). The nanostructured scaffolds with large pores were constructed by using particle-leaching method (100-300 um glucose) to produce pores. The polymer co-solvent system had high variability, in which the polymer may be replaced with polylactide, polycaprolactone and polyester polyurethane, and the relatively poor solvent of the co-solvent may be replaced by N,N-dimethylacetamide, tetrahydrofuran, dimethyl sulfoxide and acetone. With the controllable process, a high reproducibility was achieved facilely. These nanostructured scaffolds with large pores were expected to have potential applications in tissue engineering. In addition, the hydrophilicity and antibacterial properties was improved by PLA nanofibrous (<100 nm in fiber diameter) membranes grafted with chitosan or sulfonated chitosan by air plasma treated.