心肌梗塞是一種急性的心臟疾病，其最常見的成因為冠狀狹窄或阻塞，心肌細胞無法透過冠狀動脈獲得足夠的氧氣和養分而壞死。在心肌梗塞的區域中，壞死的心肌細胞會逐漸形成纖維化的成疤組織(scar tissue)。取而代之的纖維化組織缺乏正常心肌細胞中電訊號傳遞的功能，進而導致心律不整甚至心臟功能的喪失。在本論文中，我們將導電性高分子聚3-氨基-4-甲氧基苯甲酸(poly-3-mino-4-methoxybenzoic acid, PAMB)接枝於明膠(gelatin)上並利用1-乙基-(3-二甲基氨基丙基)碳酰二亞胺鹽酸鹽(1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, EDC)搭配N-羥基琥珀醯亞胺(n-hydroxysuccinimide, NHS)交聯製備出具生物相容性的自我摻雜導電性水膠(Gel-PAMB)，期望將材料注射於心臟梗塞患部幫助心肌電訊號的傳遞，使心臟同步收縮，達到心臟功能恢復之目的。在體外實驗裡，我們分別以鈣離子指示劑Ca2+ indicator及微電極陣列證實了自我摻雜導電性水膠Gel-PAMB具有協助心肌細胞的電訊號耦合及電訊號傳遞能力。而在動物實驗裡，我們以外科手術方式將大鼠冠狀動脈結紮，建立心肌梗塞的模型後，將開發的導電性水膠注射至纖維化的成疤組織周圍，並使用心電圖、光學影像映射系統、心臟超音波、體外微電極陣列等分析大鼠心臟功能的恢復。我們發現注射自我摻雜導電性水膠Gel-PAMB後能有效的恢復心臟功能，包括了心律不整現象的減輕、心臟電訊號傳遞速率上升及左心收縮力增強。由以上實驗結果可知，本論文所開發出的自我摻雜導電性水膠Gel-PAMB能有效地連接成疤組織處阻斷的心肌電訊號，進而同步心肌收縮，恢復心臟功能，具有應用於心肌梗塞疾病治療的潛能。

Myocardial infarction (MI) induces permanent loss of cardiomyocytes and forms fibrous scar tissues. The nonconductive nature of fibrous scar tissues can cause desynchronized cardiac contraction, owing to the electrically uncoupling viable cardiomyocytes in the infarct region. In this work, a self-doping conductive polymeric hydrogel (Gel-PAMB) was synthesized by grafting the conductive poly-3-amino-4- methoxybenzoic acid (PAMB) on biocompatible gelatin (Gel) and then crosslinked by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) in combination with N-hydroxysuccinimide (NHS), which can be injected to the MI tissues to support electric conduction, thus improving cardiac function. The results of the in vitro study demonstrated that Gel-PAMB enhanced electrical signaling propagation and electrical coupling between cardiomyocytes, as confirmed through the calcium signaling analysis and microelectrode arrays. Furthermore, The Gel-PAMB was injected into the MI area of rats, and the preliminary in vivo experiments showed that a significant improvement of heart functions, such as reduced spontaneous arrhythmia, improved conduction velocity, and increased fractional shortening, was achieved as compared to Gel treatment. Overall, both in vitro and in vivo results clearly suggests that the Gel-PAMB can synchronize cardiac contraction by electrically bridging isolated viable cardiomyocytes within the scar tissues, restoring the global heart function. The use of this novel injectable conductive hydrogel may provide a new therapy strategy for the treatment of MI.

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