| 摘要: | 由於其在許多生物醫學應用中的潛力，包括組織修復和再生、藥物管理、抗菌和防污應用，仿生兒茶酚功能化水凝膠受到了廣泛的關注。
在第二章中，多巴胺被開發為光引髮劑，利用一鍋法製備功能性兒茶酚胺水凝膠。 根據偽一級動力學，多巴胺在酸性溶液中在紫外線照射下產生自由基，最有可能是半醌自由基，以引發加成聚合。 多巴胺引發的光聚合提供了一種簡單直接的方法，同時還防止了兒茶酚基團的不利氧化。 為了創建生物相容性水凝膠，使用了超親水性磺基甜菜鹼甲基丙烯酸酯（SBMA）。 為了研究聚合機理以及pH、UV劑量和多巴胺濃度方面的理想實驗環境，進行了1H核磁共振、紫外-可見光譜、凝膠滲透色譜和流變學測試。 所得兒茶酚官能化 pSBMA 水凝膠的機械特性、自愈性和可注射性、高粘附性和抗污染性均有所提高，證明了其特殊品質。 因此，創建兒茶酚胺水凝膠的合成方法可以有利於多巴胺在許多應用中的利用。
第三章的研究目標是創建一種改性技術，使鎳鈦諾合金上的一致兒茶酚輔助兩性電離成為可能，從而實現生物相容性和抗污染性。多巴胺引發的光聚合用於生成兒茶酚官能化的聚磺基甜菜鹼甲基丙烯酸酯 (pSBMA/DA)。 多巴胺（DA）在紫外線照射下產生的半醌自由基抑制pH 2溶液的分子內環化和分子間二聚化失去電子。 揭示了 pSBMA/DA 光聚合中的準一級聚合動力學以及數均分子量和表觀速率常數之間的關係。 PSBMA/DA 在 pH 值為 3 的溶液中開始聚集，防止兒茶酚部分過早氧化，並能夠均勻沉積在鎳鈦諾基材上。 當 pSBMA/DA 在 pH 調節至 8.5 後延伸時，兒茶酚部分通過形成雙齒結合被觸發與鎳鈦諾表面相互作用。 根據 X 射線光電子能譜 (XPS) 研究，較短的 pSBMA/DA 鍊和較高的兒茶酚含量可提供更多的錨定位點，從而提高兩性離子部分在底物上的覆蓋率。 有趣的是，在原子力顯微鏡 (AFM) 圖片中發現基於 pH 轉換方法的 pSBMA/DA 沉積是均勻且光滑的。 鎳鈦合金表面 pSBMA/DA 塗層的強離子水合作用可防止非特異性生物污垢吸附，並具有出色的防污能力。 經兩性離子處理的鎳鈦諾對金黃色葡萄球菌和大腸桿菌的粘附率降低99.9%。 此外，在培養條件下孵育24小時後，pSBMA/DA對NIH 3T3小鼠成纖維細胞表現出很強的防污性能。 綜合考慮，通過 pH 轉變技術的 pSBMA/DA 塗層為促進防污和塗層技術的均勻表面功能化提供了一種有前途的方法。
第四章討論了生物污垢如何粘附在各種表面上並通過傳播醫院感染來損害工業設施、醫療設備和/或醫院的功能。 兩性離子化合物的表面固定化可以阻止污染物的初始粘附，但其應用並不廣泛。 在這項研究中，我們提供了一種簡單、通用的兩步表面改性方法來提高抗污性。 為了創建“底漆”層（PDA/PEI），在第一階段將基材浸入含有多巴胺和支化聚乙烯亞胺（PEI）的共沉積溶液中。 PEI 的伯胺、仲胺和叔胺部分在第二步中被 1,3-丙烷磺內酯甜菜化，從而在底物上產生兩性離子。 甜菜鹼化後，經過開環烷基化反應的PS接枝PDA/PEI（PDA/PEI/S）的潤濕性發生了變化。 根據X射線光電子能譜，發現由PDA/PEI/S製成的表面具有兩性離子部分。 使用橢圓光度術和原子力顯微鏡進一步研究了 PEI 含量、薄膜厚度、底漆穩定性和甜菜鹼化之間的關係。 在理想條件下製造的兩性離子修飾的基材可以表現出強大的抗細菌污染能力，細菌粘附減少 98.5%。 該技術還展示了與基材無關的特性，可以在有機和無機表面上成功應用。 最後但並非最不重要的一點是，最近發現的方法表現出出色的生物相容性，與空白對照樣品沒有明顯的差異。 總的來說，我們相信簡單的表面改性技術將有助於推動未來兩性離子裝飾材料的生產。
第五章將討論貽貝類材料的應用研究。 由磷酸甜菜鹼 MPC 單體和兒茶酚 DMA 單體組成的 P(MPC-co-DMA) 共聚物被研究作為乾眼病 (DED) 的潛在局部治療方法。 該共聚物通過無規自由基共聚合成，產生不同程度的 DMA 官能化。 由於兒茶酚殘留，共聚物表現出粘膜粘附特性，引起粘蛋白吸光度最大值（UV-VIS）的紅移以及粘蛋白沉積表面上吸附質量密度的增加。 有趣的是，局部滴注 4 天后，p(MPC-co-DMA) 促進了兔眼眼表的牢固粘附。 在藥理作用方面，該共聚物表現出優異的抗氧化和抗炎作用，清除細胞內活性氧（ROS）並抑制炎症因子表達和細胞凋亡。 結果，DED 誘導的兔眼表現出淚膜穩定性和淚液分泌增強，表明有恢復的跡象。 展望未來，p(MPC-co-DMA)可以進一步用活性試劑（如抗體、抗生素）進行後修飾，以增強其抗菌活性或用作藥物載體。
;Due to their potential in a number of bio-medical applications, including tissue repair and regeneration, drug administration, antimicrobial and antifouling applications, biomimetic catechol-functionalized hydrogels have received a lot of interest.
Dopamine was developed as a photo-initiator in chapter II to create functional catecholamine hydrogels utilizing a one-pot method. Dopamine produces free radicals under UV irradiation in an acidic solution, most likely semiquinone radicals, to initiate the addition polymerization, according to pseudo first-order kinetics. Dopamine-initiated photopolymerization offers a simple and straightforward method while also preventing the unfavorable oxidation to catechol groups. For the creation of biocompatible hydrogels, superhydrophilic sulfobetaine methacrylate (SBMA) was used. In order to investigate the polymerization mechanism and the ideal experimental circumstances in terms of pH, UV dosages, and dopamine concentration, 1H nuclear magnetic resonance, UV-vis spectroscopy, gel permeation chromatography, and rheological tests were carried out. The increased mechanical characteristics, self-healing and injectability, high adhesiveness, and fouling resistance of the resulting catechol-functionalized pSBMA hydrogels were evidence of their special qualities. As a result, the synthetic approach to creating catecholamine hydrogels can benefit the utilization of dopamine in a number of applications.
The study′s goal in chapter III is to create a modification technique that will make consistent catechol-assisted zwitterionization on nitinol alloy possible for biocompatibility and fouling resistance. Dopamine-initiated photo-polymerization is used to create catechol-functionalized polysulfobetaine methacrylate (pSBMA/DA). Semiquinone radicals produced from dopamine (DA) under UV irradiation inhibited pH 2 solution intramolecular cyclization and intermolecular dimerization from losing an electron. It is revealed how pseudo-first-order polymerization kinetics and relationships between the number average molecular weight and apparent rate constant in photopolymerization for pSBMA/DA. PSBMA/DA starts to aggregate in a solution with a pH of 3, preventing catechol moieties from early oxidation and enabling even deposition on the nitinol substrate. Catechol moieties are triggered to interact with the nitinol surface via the creation of bidentate binding as pSBMA/DA extends after pH adjustment to 8.5. A shorter pSBMA/DA chain with a higher catechol content offers more anchoring sites to improve the coverage of zwitterionic moieties on substrates, according to X-ray photoelectron spectroscopy (XPS) study. Interesting, pH-transition method-based pSBMA/DA deposition was seen in atomic force microscopy (AFM) pictures to be homogeneous and smooth. Strong ionic hydration of the pSBMA/DA coating on the surface of nitinol prevents non-specific bio-foulant adsorption and allows for outstanding antifouling capabilities. Nitinol treated with zwitterion has a 99.9% decrease rate for Staphylococcus aureus and Escherichia coli adhesion. Additionally, after 24 hours of incubation, pSBMA/DA displays a strong antifouling performance against NIH 3T3 mouse fibroblasts in culture conditions. All things considered, the pSBMA/DA coating via pH transition technique offers a promising method for facilitating homogeneous surface functionalization for antifouling and coating technology. In chapter IV, it is discussed how biofoulants can stick to various surfaces and impair the functionality of industrial facilities, medical devices, and/or hospitals by spreading nosocomial infections. Surface immobilization of zwitterionic compounds can stop the foulants′ initial adhesion, but it is not widely used. In this research, we provide a simple, universal two-step surface modification method to increase fouling resistance. To create a "primer" layer (PDA/PEI), the substrates were submerged in a co-deposition solution containing dopamine and branching polyethyleneimine (PEI) in the first phase. The primary, secondary, and tertiary amine moieties of PEI were betainized by 1,3-propane sultone in the second step, resulting in zwitterions on substrates. Following betainization, the wettability of PS-grafted PDA/PEI (PDA/PEI/S) with ring-opening alkylation reaction changed. Surfaces made of PDA/PEI/S were found to have zwitterionic moieties according to X-ray photoelectron spectroscopy spectra. The relationship between PEI content, film thickness, primer stability, and betainization was further examined using ellipsometry and atomic force microscopy. Zwitterion-decorated substrates created under ideal conditions can display great resistance against bacterial fouling, attaining a 98.5% reduction in bacterial adhesion. The technique also demonstrates a substrate-independent property, permitting successful application on both organic and inorganic surfaces. Last but not least, the recently discovered method exhibits outstanding biocompatibility, showing no discernible difference from blank control samples. Overall, we believe that the simple surface modification technique will help advance the production of materials ornamented with zwitterion in the future.
In chapter V, application-oriented research on mussel-inspired material will be discussed. P(MPC-co-DMA) copolymers, composed of phosphobetaine MPC monomer and catechol DMA monomer, were investigated as a potential topical treatment for dry eye disease (DED). The copolymers were synthesized via random free-radical copolymerization, producing different degrees of DMA functionalization. Owing to the catechol residues, the copolymers exhibited mucoadhesive properties, inducing a red shift in mucin absorbance maxima (UV-VIS) and an increase in adsorbed mass density on the mucin-deposited surface. Interestingly, p(MPC-co-DMA) facilitated robust adhesion on the ocular surface of the rabbit eye after 4 days of topical instillation. For pharmacological effect, the copolymers demonstrated excellent anti-oxidant and anti-inflammatory, scavenging intracellular reactive oxygen species (ROS) and inhibiting inflammatory factor expression and cell apoptosis. As a result, DED-induced rabbit eyes exhibited enhanced tear film stability and lacrimal fluid secretion, suggesting signs of recovery. For future perspective, p(MPC-co-DMA) can be further post-modify with active reagents (such as antibodies, antibiotics) for enhancing their antibacterial activity or use as a drug carrier. |
