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研究生: 阮黃素然
Nguyen Hoang To Nhien
論文名稱: 可促進傷口癒合並無創監測其癒合過程之智能型敷料
A Smart Electroactive Dressing Integrated with a Self-Powered System That Can Promote Wound Healing and Noninvasively Monitor Its Healing Progress
指導教授: 宋信文
Sung, Hsing-Wen
口試委員: 林宗宏
蘇慕寰
胡宇方
劉培毅
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2021
畢業學年度: 109
語文別: 英文
論文頁數: 35
中文關鍵詞: 導電性敷料傷口癒合奈米磨擦發電機傷口癒合監測遠程醫療自供電傳感器
外文關鍵詞: electroactive dressing, wound healing, triboelectric nanogenerator, wound healing monitoring, telemedicine, self-powered sensor
相關次數: 點閱:2下載:0
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  • 傳統傷口敷料缺乏促進細胞活動及監測傷口癒合能力,因此,本實驗設計一種具導電性的水凝膠敷料以解決這些問題。敷料由膠原蛋白膜、聚多巴胺交聯羧甲基殼聚醣(polydopamine-crosslinked carboxymethyl chitosan)的導電水凝膠層和指插式電極 (interdigitated array electrode, IDA)所組成,並將敷料敷在小鼠傷口上。導電水凝膠可作為傷口部位的電信號傳遞媒介,刺激傷口周圍的細胞,加速受傷組織恢復;在此同時,此導電敷料亦可利用無創方式監測傷口癒合進度。將水凝膠層上的指插式電極(IDA)與傳統電源或自供電奈米磨擦發電機(self-powered triboelectric nanogenerator)串聯,即可檢測受傷組織的電阻及輸出電流,此監測系統藉由WIFI,並搭載智慧型手機的應用程式進行數據收集和傳輸。該裝置可方便患者於日常生活中佩戴,並對潛在的感染狀況發出即時警訊,無線發送傷口恢復數據至遠端醫護人員進行動態監測,以實現遠程醫療。


    Traditional wound dressings lack the abilities of promoting cellular activities that heal wounds and assisting in monitoring the progress of that healing. To address these concerns, an engineered electroactive dressing, which comprises a backing film of collagen, a layer of polydopamine-crosslinked carboxymethyl chitosan conductive hydrogel, and an interdigitated array (IDA) electrode, is developed and evaluated in a mouse model with a full-thickness skin defect. The incorporated conductive hydrogel offers a channel for electrical signal transmission at the wound site, stimulating electrical-stimuli responsive cells, accelerating the restoration of the wounded tissue. The IDA electrode, which is connected in series with a conventional power source or a self-powered triboelectric nanogenerator, is able to detect the electrical resistance or output current across the wounded tissue for monitoring its healing progress noninvasively. This wound monitoring system is integrated with a WIFI-based system for wireless data collection and transmission, using a personal smartphone that is installed with an app program. Such a real-time wound monitoring system can be worn by patients in everyday life and issue early warnings to them for potential infection as well as wirelessly sending wound progression data to the remote medical staff for dynamic intervention, implementing telemedicine.

    Contents Abstract i Contents iii List of Figure v List of Tables vii Chapter 1: Introduction 1 1.1. Conductivity in Wound Healing Process 1 1.1.1. Endogenous Electric Fields in Wound Region 1 1.1.2. Polymeric Conductive Materials in Wound Healings 2 1.2. Wound Healing Monitoring 3 1.3. Introduction of PDA-CMC Conducting Polymer 3 1.3.1. Introduction of Carboxymethyl Chitosan (CMC) 3 1.3.2. Introduction of Polydopamine (PDA) 4 1.4. Introduction of Triboelectric nanogenerator 5 1.5. Designing of The Electroactive Dressing Integrated with a Self-Powered System That Can Promote Wound Healing and Noninvasively Monitor Its Healing Progress 5 1.5.1. Purpose of Research 5 1.5.2. Experiment Design 7 Chapter 2: Materials and methods 8 2.1. Materials 8 2.2. Synthesis and Characterization of Conductive Hydrogel 8 2.2.1. Preparation of CMC 8 2.2.2. Preparation of PDA-CMC Hydrogel 8 2.3. Hydrogel Optimization 8 2.3.1. Gelation time 8 2.3.2. Conductivity of PDA-CMC 9 2.4. Adhesiveness of PDA-CMC 9 2.5. Antioxidant Activity of PDA-CMC 9 2.6. In Vitro Study 9 2.6.1. Hemocompatibility of PDA-CMC 9 2.6.2. Cytocompatibility of PDA-CMC 10 2.7. In Vivo Study 10 2.7.1. Preparation of IDA Electrodes 10 2.7.2. Animal Studies 10 2.7.3. Histological Examination 11 2.7.4. Immunohistochemistry Staining and Collagen Deposition 11 2.7.5. Wound Healing Monitoring 11 Chapter 3: Result and discussion 13 3.1. Synthesis and Characterization of CMC and PDA-CMC 13 3.2. Hydrogel Optimization 14 3.2.1. Gelation time 14 3.2.2. Conductivity of PDA-CMC 14 3.3. Adhesivness 15 3.4. Antioxidant 16 3.5. In Vitro Study 16 3.5.1. Hemocompatibility 16 3.5.2. Cyotoxicities 17 3.6. In Vivo Study 18 3.6.1. Wound Area Contraction 18 3.6.2. H&E Staining, Immunofluorescence Staining and Collagen Deposition 20 3.6.3. Wound Healing Monitoring 21 Chapter 4: Summary and Conclusion 30 References 31

    [1] Thomas S. Kupper and Robert C. Fuhlbrigge (2004), Immune surveillance in the skin: mechanisms and clinical consequences, Nature Reviews Immunology, 4, 211–222.
    [2] Manolis Pasparakis, Ingo Haase and Frank O. Nestle (2014), Mechanisms regulating skin immunity and inflammation, Nature Reviews Immunology, 14, 289–301.
    [3] Chiranjeevi Korupalli, Hui Li, Nhien Nguyen, Fwu-Long Mi, Yen Chang, Yu-Jung Lin, Hsing-Wen Sung (2020), Conductive Materials for Healing Wounds: Their Incorporation in Electroactive Wound Dressings, Characterization, and Perspectives, Advanced Healthcare Materials, 10, 2001384.
    [4] Richard Nuccitelli (2003), A Role for Endogenous Electric Fields in Wound Healing, Current Topics in Developmental Biology, 58, 1–26.
    [5] M. Zhao (2009), Electrical fields in wound healing-An overriding signal that directs cell migration, Seminars in Cell & Developmental Biology, 20, 674–682.
    [6] Véronique J. Moulin, Jean Dubé, Olivier Rochette-Drouin, Philippe Lévesque, Robert Gauvin, Charles J. Roberge, François A. Auger, Daniel Goulet, Michel Bourdages, Michel Plante, and Lucie Germain (2012), Electric Potential Across Epidermis and Its Role During Wound Healing Can Be Studied by Using an In Vitro Reconstructed Human Skin, Advances in Wound Care, 1, 81–87.
    [7] Alan G. MacDiarmid (2001), “Synthetic Metals”: A Novel Role for Organic Polymers, Angewandte Chemie (International ed.), 40, 2581–2590.
    [8] Baolin Guo, Peter X. Ma (2018), Conducting Polymers for Tissue Engineering, Biomacromolecules, 19, 1764–1782.
    [9] Azadeh Saberi, Farzaneh Jabbari, Payam Zarrintaj, Mohammad Reza Saeb and Masoud Mozafari (2019), Electrically Conductive Materials: Opportunities and Challenges in Tissue Engineering, Biomolecules, 9, 448.
    [10] MilenaTalikowska, Xiaoxu Fu and Grzegorz Lisak (2019), Application of conducting polymers to wound care and skin tissue engineering: A review Biosensors and Bioelectronics, 135, 50–63
    [11] Anita F. Quigley, Joselito M. Razal, Brianna C. Thompson, Simon E. Moulton, Magdalena Kita, Elizabeth L. Kennedy, Graeme M. Clark, Gordon G. Wallace, Robert M. I. Kapsa (2009), A Conducting-Polymer Platform with Biodegradable Fibers for Stimulation and Guidance of Axonal Growth, Advanced Materials, 21, 4393–4397.
    [12] Abdurrahman Gumus, Joseph P. Califano, Alwin M. D. Wan, John Huynh, Cynthia A, Reinhart-King, George G. Malliaras (2010), Control of cell migration using a conducting polymer device, Soft Matter, 6, 5138–5142.
    [13] Milena Talikowska, Xiaoxu Fu, Grzegorz Lisak (2019), Application of conducting polymers to wound care and skin tissue engineering: A review, Biosensors and Bioelectronics, 135, 50–63.
    [14] Russell Urie, Deepanjan Ghosh, Inam Ridha, Kaushal Rege (2018), Inorganic Nanomaterials for Soft Tissue Repair and Regeneration, Annual Review of Biomedical Engineering, 20, 353–374.
    [15] Susheel Kumar Nethi, Sourav Das, Chitta Ranjan Patra, Sudip Mukherjee (2019), Recent advances in inorganic nanomaterials for wound-healing applications, Biomaterials Science, 7, 2652–2674.
    [16] Ali Tamayol, Mohsen Akbari, Yael Zilberman, Mattia Comotto, Emal Lesha, Ludovic Serex, Sara Bagherifard, Yu Chen, Guoqing Fu, Shideh Kabiri Ameri, Weitong Ruan, Eric L Miller, Mehmet R Dokmeci, Sameer Sonkusale, Ali Khademhosseini (2016), Flexible pH-Sensing Hydrogel Fibers for Epidermal Applications, Advanced Healthcare Materials, 5, 711–719.
    [17] Yingnan Zhu, Jiamin Zhang, Jiayin Song, Jing Yang, Zheng Du, Weiqiang Zhao, Hongshuang Guo, Chiyu Wen, Qingsi Li, Xiaojie Sui, Lei Zhang (2020), A Multifunctional Pro-Healing Zwitterionic Hydrogel for Simultaneous Optical Monitoring of pH and Glucose in Diabetic Wound Treatment, Advanced Functional Materials, 30, 1905493.
    [18] Lingling Zhao, Lijing Niu, Hongze Liang, Hui Tan, Chaozong Liu, Feiyan Zhu (2017), pH and Glucose Dual-Responsive Injectable Hydrogels with Insulin and Fibroblasts as Bioactive Dressings for Diabetic Wound Healing, ACS Applied Materials & Interfaces, 9, 37563–37574.
    [19] Saghi Saghazadeh, Chiara Rinoldi, Maik Schot, Sara Saheb Kashaf, Fatemeh Sharifi, Elmira Jalilian, Kristo Nuutila, Giorgio Giatsidis, Pooria Mostafalu, Hossein Derakhshandeh, Kan Yue, Wojciech Swieszkowski, Adnan Memic, Ali Tamayol, Ali Khademhosseini (2018), Drug delivery systems and materials for wound healing applications, Advanced Drug Delivery Reviews, 127, 138–166
    [20] Pooria Mostafalu, Ali Tamayol, Rahim Rahimi, Manuel Ochoa, Akbar Khalilpour, Gita Kiae, Iman K Yazdi, Sara Bagherifard, Mehmet R Dokmeci, Babak Ziaie, Sameer R Sonkusale, Ali Khademhosseini (2018), Smart Bandage for Monitoring and Treatment of Chronic Wounds, Small, e1703509.
    [21] Sohini RoyChoudhury, Yogeswaran Umasankar, Jose Jaller, Ingrid Herskovitz, Joshua Mervis, Evan Darwin, Penelope A. Hirt, Luis J. Borda, Hadar A. Lev-Tov, Robert Kirsner, Shekhar Bhansali (2018), Continuous monitoring of wound healing using a wearable enzymatic uric acid biosensor, Journal of the Electrochemical Society, 165, B3168–B3175.
    [22] ZahraShariatinia (2018), Carboxymethyl chitosan: Properties and biomedical applications, International Journal of Biological Macromolecules, 120, 1406–1419.
    [23] Sikai Peng, Wanshun Liu, Baoqin Han, Jing Chang, Minyu Li and Xuan Zhi (2010), Carboxymethyl chitosan nanoparticles loaded with bioactive peptide OH-CATH30 benefit nonscar wound healing, Journal of Ocean University of China, 10, 369–378.
    [24] Tongyi Sun, Bo Zhan, Weifen Zhang, Di Qin, Guixue Xia, Huijie Zhang, Meiyu Peng, Sheng-An Li, Yun Zhang, Yuanyuan Gao and Wen-Hui Lee (2018), Effects of carboxymethyl-chitosan on wound healing in vivo and in vitro, International Journal of Nanomedicine, 13, 5771–5786.
    [25] Weijuan Huang, Yixiang Wang, Zhiqiang Huang, Xiaolan Wang, Lingyun Chen, Yu Zhang and Lina Zhang (2018), On-Demand Dissolvable Self-Healing Hydrogel Based on Carboxymethyl Chitosan and Cellulose Nanocrystal for Deep Partial Thickness Burn Wound Healing, ACS Applied Materials and Interfaces, 10, 41076–41088.
    [26] Chia-Yu Liu, Chun-Jen Huang (2016), Functionalization of Polydopamine via the Aza-Michael Reaction for Antimicrobial Interfaces, Langmuir, 32, 5019–5028.
    [27] Shilin Mei, Xiaohui Xu, Rodney D. Priestley, Yan Lu (2020), Polydopamine-based nanoreactors: synthesis and applications in bioscience and energy materials, Chemical Science, 11, 12269–12281.
    [28] Yongping Liang, Xin Zhao, Tianli H, Yong Han, Baolin Guo (2019), Mussel-inspired, antibacterial, conductive, antioxidant, injectable composite hydrogel wound dressing to promote the regeneration of infected skin, Journal of Colloid and Interface Science, 556, 514–528
    [29] Lu Han, Liwei Yan, Kefeng Wang, Liming Fang, Hongping Zhang, Youhong Tang, Yonghui Ding, Lu-Tao Weng, Jielong Xu, Jie Weng, Yujie Liu, Fuzeng Ren and Xiong Lu (2017), Tough, self-healable and tissue-adhesive hydrogel with tunable multifunctionality, NPG Asia Materials, 9, 372.
    [30] Pengfei Tang, Lu Han, Pengfei Li, Zhanrong Jia, Kefeng Wang, Hongping Zhang, Hui Tan, Tailin Guo, Xiong Lu (2019), Mussel-Inspired Electroactive and Antioxidative Scaffolds with Incorporation of Polydopamine-Reduced Graphene Oxide for Enhancing Skin Wound Healing, ACS Applied Materials and Interfaces, 11, 7703–7714.
    [31] Yun Ting Jao, Po Kang Yang, Che Min Chiu, Yu Jhen Lin, Shuo Wen Chen, Dongwhi Choi, Zong Hong Lin (2018), A textile-based triboelectric nanogenerator with humidity-resistant output characteristic and its applications in self-powered healthcare sensors, Nano Energy, 50, 513–520.
    [32] Zong Hong Lin, Wei Shan Hsu, Anant Preet, Li Hsien Yeh, Yung Hsin Chen, Yu Ping Pao, Shien Fong Lin, Sangmin Lee, Jia Ching Fan, Ligang Wang, Yi Pin Chiu, Bak Sau Yip, Tzu En Lin (2021), Ingestible polysaccharide battery coupled with a self-charging nanogenerator for controllable disinfection system, Nano Energy, 79, 105440.
    [33] Zhuo Liu, Hu Li, Bojing Shi, Yubo Fan, Zhong Lin Wang, Zhou Li (2019), Wearable and Implantable Triboelectric Nanogenerators, Advanced Functional Materials, 29, 1808820.
    [34] Long Jin, Xiao Xiao, Weili Deng, Ardo Nashalian, Daren He, Vidhur Raveendran, Cheng Yan, Hai Su, Xiang Chu, Tao Yang, Wen Li, Weiqing Yang, Jun Chen (2020), Manipulating Relative Permittivity for High-Performance Wearable Triboelectric Nanogenerators, Nano Letter, 20, 6404–6411.
    [35] Haobin Wang, Mengdi Han, Yu Song, Haixia Zhang (2021), Design, manufacturing and applications of wearable triboelectric nanogenerators, Nano Energy, 81, 105627.
    [36] Xiao Fei Liu, Yun Lin Guan, Dong Zhi Yang, Zhi Li, Kang De Yao (2001), Antibacterial action of chitosan and carboxymethylated chitosan, Journal of Applied Polymer Science, 79, 1324.
    [37] Xin Zhao, Yongping Liang, Ying Huang, Jiahui He, Yong Han, Baolin Guo (2020), Physical Double-Network Hydrogel Adhesives with Rapid Shape Adaptability, Fast Self-Healing, Antioxidant and NIR/pH Stimulus-Responsiveness for Multidrug-Resistant Bacterial Infection and Removable Wound Dressing, Advanced Functinal Materials, 30, 1910748.
    [38] Xin Jing, Hao-Yang Mi, Brett N.Napiwocki, Xiang-Fang Peng, Lih-Sheng Turng (2017), Mussel-inspired electroactive chitosan/graphene oxide composite hydrogel with rapid self-healing and recovery behavior for tissue engineering, Carbon, 125, 557–570.
    [39] Marko Mihajlovic, Milos Mihajlovic, Patricia Y. W. Dankers, Rosalinde Masereeuw, Rint P Sijbesma (2018), Carbon Nanotube Reinforced Supramolecular Hydrogels for Bioapplications, Macromolecular Bioscience, 19, e1800173.
    [40] Jin Qu, Xin Zhao, Yongping Liang, Yameng Xu, Peter X.Ma, Baolin Guo (2019), Degradable conductive injectable hydrogels as novel antibacterial, anti-oxidant wound dressings for wound healing, Chemical Engineering Journal, 362, 548–560.
    [41] Chongyu Zhang, Meng-Hsuan Hsieh, Song-Yi Wu, Shu-Hong Li, Jun Wu, Shi-Ming Liu, Hao-Ji Wei, Richard D Weisel, Hsing-Wen Sung, Ren-Ke Li, A self-doping conductive polymer hydrogel that can restore electrical impulse propagation at myocardial infarct to prevent cardiac arrhythmia and preserve ventricular function, Biomaterials, 231, 119672.
    [42] Shaohan Zhang, Jingyi Hou, Qijuan Yuan, Peikun Xin, Huitong Cheng, Zhipeng Gu, Jun Wu (2020), Arginine derivatives assist dopamine-hyaluronic acid hybrid hydrogels to have enhanced antioxidant activity for wound healing, Chemical Engineering Journal, 392, 123775.
    [43] Jagdeep Kumar, Naresh Kumar, Nitin Sati, Prasanta Kumar Hota (2020), Antioxidant properties of ethenyl indole: DPPH assay and TDDFT studies, New Journal of Chemistry, 44, 8960–8970
    [44] Yue Zhao, Zuhao Li, Shanliang Song, Kerong Yang, Hou Liu, Zhe Yang, Jincheng Wang, Bai Yang, Quan Lin (2019), Skin-Inspired Antibacterial Conductive Hydrogels for Epidermal Sensors and Diabetic Foot Wound Dressings, Advanced Functional Materials, 29, 1901474.
    [45] D Warren Spence, Bruce Pomeranz (1996), Surgical wound healing monitored repeatedly in vivo using electrical resistance of the epidermis, Physiological Measurement, 17, 57.
    [46] Xiachuan Pei, Hao Jin, Shurong Dong, Dong Lou, Lie Ma, Xingang Wang, Weiwei Cheng, Hei Wong (2019), Flexible wireless skin impedance sensing system for wound healing assessment, Vacuum, 168, 108808.
    [47] Xinxin Fang, Qinghui Jin, Fengxiang Jing, Huanqian Zhang, Feng Zhang, Hongju Mao, Baojian Xu, Jianlong Zhao (2013), Integrated biochip for label-free and real-time detection of DNA amplification by contactless impedance measurements based on interdigitated electrodes, Biosensors and Bioelectronics, 44, 241–247.
    [48] Shanshan Yao, Amanda Myers, Abhishek Malhotra, Feiyan Lin, Alper Bozkurt, John F. Muth, Yong Zhu (2017), Hydration Sensing: A Wearable Hydration Sensor with Conformal Nanowire Electrodes, Advanced Healthcare Materials, 6, 1601159.
    [49] Jawal Said, Michael Walker, David Parsons, Paul Stapleton, Anthony E.Beezer, Simon Gaisford, An in vitro test of the efficacy of an anti-biofilm wound dressing (2014),
    International Journal of Pharmaceutics, 474, 177–181.
    [50] Xiaoning Li, Hao Kong, Rubul Mout, Krishnendu Saha, Daniel F Moyano, Sandra M Robinson, Subinoy Rana, Xinrong Zhang, Margaret A Riley, Vincent M Rotello (2014), Rapid identification of bacterial biofilms and biofilm wound models using a multichannel nanosensor, ACS Nano, 8, 12014.
    [51] Xing Liu, Shiyan Zhuo, Xianyue Jing, Yong Yuan, Christopher Rensing, Shungui Zhou (2019), Flagella act as Geobacter biofilm scaffolds to stabilize biofilm and facilitate extracellular electron transfer, Biosensors and Bioelectronics, 15, 111748.

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