心血管疾病目前是世界上主要的死亡原因之一，而急性心肌梗塞（acute myocardial infarction, AMI）是一種常見的心臟疾病，其最常見的成因為冠狀狹窄或阻塞導致的心肌細胞死亡。冠狀動脈是供給心臟血液的動脈，在發生心肌梗塞後，心肌細胞因無法透過冠狀動脈獲得足夠的氧氣和養分而死亡。心肌細胞死亡後在心肌梗塞區域被纖維化的成疤組織（scar tissue）所取代。纖維化組織中死亡的心肌細胞無法與正常心肌細胞的進行電訊號的傳遞，無法形成連接從而導致心律失常。在本論文中，我們提出了一種新型的導電性生物工程補綴片，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)接枝於明膠海綿(gelfoam)上製備出具生物相容性的導電性高分子補綴片，期望將材料與細胞結合並縫合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。在體外實驗里，我們發現補綴片具有讓心肌細胞粘附、幫助細胞維持跳動頻率的作用。同時我們以鈣離子指示劑Ca2+ indicator 在熒光顯微鏡中觀察心肌細胞的同步收縮情形與相關電訊號傳遞通道蛋白的表現，證實了導電性生物工程補綴片具有協助心肌細胞的電訊號耦合與電訊號傳遞。由以上實驗結果表明，本論文所開發出的導電性生物工程補綴片，藉由PAMB上的羧基和氨基使得導電性補綴片在生理環境中具有穩定的導電度，能有效傳遞心肌細胞間的電訊號，具有應用於心臟梗塞後治療的潛能。

Cardiovascular diseases are the leading cause of death in the world, and acute myocardial infarction (AMI) is a common heart disease, most commonly due to myocardial cell death due to coronary stenosis or obstruction. Coronary arteries are the arteries that supply blood to the heart. After myocardial infarction, cardiomyocytes (CMs) cannot get enough oxygen and nutrients through the coronary arteries. The proliferating fibroblasts causes scar formation in and around the infarction. The nonconductive nature of the collagen scar tissue causes electrically uncoupling of viable CMs in the infarct region. In this work, we evaluated the conductivity and efficacy of a newly synthesized conductive poly-3-amino-4-methoxybenzoic acid (PAMB)-gelfoam (G) patch to support CM viability and function in vitro. The results of the in vitro study demonstrated that PAMB-G patch were biocompatible and provided a suitable surface for cell attachment. Meanwhile, PAMB-G patch enhanced electrical signaling propagation and electrical coupling between cardiomyocytes, as confirmed through the calcium signaling analysis. The use of this novel bio-engineered conductive patch may provide a new therapy strategy for the treatment of MI.

[1] World Health Statistics 2017: monitoring health for the SDGs in, world health organization, 2017.
[2] Francis Stuart, S., De Jesus, N., Lindsey, M., & Ripplinger, C. (2016). The crossroads of inflammation, fibrosis, and arrhythmia following myocardial infarction. Journal of Molecular And Cellular Cardiology, 91, 114-122.
[3] Heart Attack, American Heart Association, Retrieved November 23, 2015, from http://watchlearnlive.heart.org/CVML_Player.php?moduleSelect=hrta tk.
[4] Huang, C., Wei, H., Lin, K., Lin, W., Wang, C., & Pan, W. et al. (2015). Multimodality noninvasive imaging for assessing therapeutic effects of exogenously transplanted cell aggregates capable of angiogenesis on acute myocardial infarction. Biomaterials, 73, 12-22.
[5] Baum, J., Long, B., Cabo, C., & Duffy, H. (2011). Myofibroblasts cause heterogeneous Cx43 reduction and are unlikely to be coupled to myocytes in the healing canine infarct. AJP: Heart And Circulatory Physiology, 302(3), H790-H800.
[6] T. Eschenhagen, C. Fink, U. Remmers, H. Scholz, J. Wattchow , J. Weil, W. Zimmermann, H.H. Dohmen, H. Schafer, N. Bishopric, T. Wakatsuki, E.L. Elson, Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system, FASEB J, 11 (1997) 683-694.
[7] R.K. Li, Z.Q. Jia, R.D. Weisel, D.A. Mickle, A. Choi, T.M. Yau, Survival and function of bioengineered cardiac grafts, Circulation, 100 (1999) II63-69.
[8] K.L. Christman, H.H. Fok, R.E. Sievers, Q. Fang, R.J. Lee, Fibrin glue alone and skeletal myoblasts in a fibrin scaffold preserve cardiac function after myocardial infarction, Tissue Eng, 10 (2004) 403-409.
[9] A.A. Rane, K.L. Christman, Biomaterials for the treatment of myocardial infarction: a 5-year update, J Am Coll Cardiol, 58 (2011) 2615-2629.
[10] T. Sakai, R.K. Li, R.D. Weisel, D.A. Mickle, E.T. Kim, Z.Q. Jia, T.M. Yau, The fate of a tissue-engineered cardiac graft in the right ventricular outflow tract of the rat, J Thorac Cardiovasc Surg, 121 (2001) 932-942.
[11] K. Kang, L. Sun, Y. Xiao, S.H. Li, J. Wu, J. Guo, S.L. Jiang, L. Yang, T.M. Yau, R.D. Weisel, M. Radisic, R.K. Li, Aged human cells rejuvenated by cytokine enhancement of biomaterials for surgical ventricular restoration, J Am Coll Cardiol, 60 (2012) 2237-2249.
[12] Huang JH, Hu XY, Lu L, Ye Z, Zhang QY, Luo ZJ. Electrical regulation of Schwann cells using conductive polypyrrole/chitosan polymers. J Biomed Mater Res A. 2010;93A(1):164-174.
[13] Rivers TJ, Hudson TW, Schmidt CE. Synthesis of a novel, biodegradable electrically conducting polymer for biomedical applications. Adv Funct Mater. 2002;12(1):33–37.
[14] Hsiao CW, Bai MY, Chang Y, Chung MF, Lee TY, Wu CT, et al. Electrical coupling of isolated cardiomyocyte clusters grown on aligned conductive nanofibrous meshes for their synchronized beating. Biomaterials. 2013;34(4):1063–1072.
[15] Merino S, Martín C, Kostarelos K, Prato M, Vazquez E. Nanocomposite hydrogels: 3D polymer-nanoparticle synergies for on-demand drug delivery. ACS Nano. 2015;9(5):4686-97.
[16] Mihic, A., Cui, Z., Wu, J., Vlacic, G., Miyagi, Y., & Li, S. et al. (2015). A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves Cardiac Function After Implantation into Myocardial Infarct. Circulation, 132(8), 772-784.
[17] Guimard, N., Gomez, N., & Schmidt, C. (2007). Conducting polymers in biomedical engineering. Progress In Polymer Science, 32(8-9), 876-921.
[18] Kaur G, Adhikari R, Cass P, Bown M, Gunatillake P. Electrically conductive polymers and composites for biomedical applications. Rsc Adv. 2015;5(47):37553-567.
[19] Mihic A, Cui Z, Wu J, Vlacic G, Miyagi Y, Li S, et al. A Conductive polymer hydrogel supports cell electrical signaling and improves cardiac function after implantation into myocardial Infarct. Circulation. 2015;132(8):772-784.
[20] Wu YB, Wang L, Guo BL, Ma PX. Interwoven aligned conductive nanofiber yarn/hydrogel composite scaffolds for engineered 3D cardiac anisotropy. ACS Nano. 2017;11(6):5646-5659.
[21] Zhong, L., Zhang, J., Zhang, Q., Chen, M., & Huang, Z. (2017). Novel poly(aniline-co-3-amino-4-methoxybenzoic acid) copolymer for the separation and recovery of Pd(ii) from the leaching liquor of automotive catalysts. RSC Adv., 7(62), 39244-39257.