利用功能化的聚癸二酸多元醇高分子開發可生物降解的彈性水凝膠

Abstract

聚癸二酸多元醇(PPS)是一類將多元醇單體與癸二酸進行縮合聚合反應所形成具有酯鍵的熱固性彈性體。PPS具有可生物降解、生物相容性和彈性的性質，並且由於其高分子鏈中的多元醇具有羥基，PPS可進行官能基的修飾。 在此論文中，將聚乙二醇(PEG)引入PPS結構中，形成兩親性高分子PGS-co-PEG與PXS-co-PEG。PEG的加入提高了PPS的親水性，使得PGS-co-PEG與PXS-co-PEG能夠透過官能基團的修飾進一步製備具有彈性的水凝膠。 在本論文的第一部分，將降冰片烯基團(norbornene)接枝到PGS-co-PEG高分子鏈上來合成Nor_PGS-co-PEG。在具備硫醇交聯劑及光引發劑的環境下照射紫外光，能透過硫醇-降冰片烯光交聯反應來形成彈性水凝膠。我們能夠透過添加不同量的交聯劑來改變水凝膠的性能，並且展示了將Nor_PGS-co-PEG使用靜電紡絲和3D列印技術進行處理，分別製造了電紡纖維和三維結構。體外細胞研究表明，Nor_PGS-co-PEG水凝膠具有細胞相容性並支持細胞增殖。 第二部分，PXS-co-PEG的製備可用來提供更多的羥基以便官能基團的修飾。醛基團可嫁接到PXS-co-PEG上形成Ald_PXS-co-PEG。另外，使用具有氨基且具有抗菌活性的殼聚醣(Chitosan, CS)來混摻形成水凝膠。PXS-co-PEG/CS水凝膠是通過動態共價亞胺鍵製備的，動態共價鍵賦予了水凝膠自癒能力和剪切稀化特性，使水凝膠具有可注射的性質。此外，靜電紡絲技術也用來製造抗菌的PXS-co-PEG電紡纖維。 本論文成功地合成了以PPS為基礎的親水性材料，以製備具有可調控性能以及可用於生物製造的彈性水凝膠和彈性抗菌水凝膠，為組織工程的應用提供了新的材料。

Poly (polyol sebacate) (PPS) is a family of ester-bonded thermoset elastomers synthesized by reacting polyols with sebacic acid. PPS owns the properties of biodegradability, biocompatability and elasticity. However, the harsh curing conditions and limited hydrophilicity impede PPS for advanced applications. With the hydroxyl groups on polyol in the polymer chain, PPS can be modified with a number of functional groups through chemical reactions for further material processing. In this thesis, we introduced PEG segments into PPS structure, forming amphiphilic poly(glycerol sebacate)-co-poly(ethylene glycol) (PGS-co-PEG) and poly(xylitol sebacate)-co-poly(ethylene glycol) (PXS-co-PEG). With the improved hydrophilicity, PGS-co-PEG and PXS-co-PEG were able to fabricate elastic hydrogels after the modification of functional groups. In the first section, norbornene groups were grafted on PGS-co-PEG polymer chain to obtain norbornene-modified PGS-co-PEG (Nor_PGS-co-PEG). The elastic PGS-co-PEG hydrogels were fabricated in the presence of dithiol crosslinker (EDT) and photoinitiator (I2959) under UV irradiation. We demonstrated the properties of PGS-co-PEG hydrogels could be modulated by adding different amount of crosslinker. Nor_PGS-co-PEG could be processed into microfibrous scaffolds and printed structures using electrospinning and 3D printing techniques, respectively. Also, in vitro cellular studies showed that Nor_PGS-co-PEG hydrogels were biocompatible and supporting cell proliferation. In the second section, PXS-co-PEG were synthesized to provide more hydroxyl groups in the structure for the modification of functional groups. Aldehyde groups were grafted on PXS-co-PEG backbone to obtain aldehyde-modified PGS-co-PEG (Ald_PXS-co-PEG). In addition, chitosan (CS) with amino groups were used for the formation of hydrogel and also provided antibacterial activity. PXS-co-PEG/ CS hydrogel was fabricated through reacting aldehyde groups with amino groups to form dynamic covalent imine bonds. The dynamic covalent bonds endowed hydrogel self-healing ability and shear thinning property, allowing the hydrogels to be injected. In addition, electrospinning techniques were used to prepare antibacterial PXS-co-PEG scaffolds. In this thesis, water soluble PPS-based materials have been successfully synthesized and functionalized to fabricate elastic hydrogels and elastic antibacterial hydrogels with definable properties. In particular, these materials were also capable of being used for bio-fabricated process, presenting a great potential for tissue engineering applications.