Bio‐Conductive Polymers for Treating Myocardial Conductive Defects: Long‐Term Efficacy Study
Following myocardial infarction (MI), the resulting fibrotic scar is nonconductive and leads to ventricular dysfunction via electrical uncoupling of the remaining viable cardiomyocytes. The uneven conductive properties between normal myocardium and scar tissue result in arrhythmia, yielding sudden c...
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description | Following myocardial infarction (MI), the resulting fibrotic scar is nonconductive and leads to ventricular dysfunction via electrical uncoupling of the remaining viable cardiomyocytes. The uneven conductive properties between normal myocardium and scar tissue result in arrhythmia, yielding sudden cardiac death/heart failure. A conductive biopolymer, poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin (PAMB‐G), is able to resynchronize myocardial contractions in vivo. Intravenous PAMB‐G injections into mice show that it does not cause any acute toxicity, up to the maximum tolerated dose (1.6 mL kg−1), which includes the determined therapeutic dose (0.4 mL kg−1). There is also no short‐ or long‐term toxicity when PAMB‐G is injected into the myocardium of MI rats, with no significant changes in body weight, organ–brain ratio, hematologic, and histological parameters for up to 12 months post‐injection. At the therapeutic dose, PAMB‐G restores electrical conduction in infarcted rat hearts, resulting in lowered arrhythmia susceptibility and improved cardiac function. PAMB‐G is also durable, as mass spectrometry detected the biopolymer for up to 12 months post‐injection. PAMB‐G did not impact reproductive organ function or offspring characteristics when given intravenously into healthy adult rats. Thus, PAMB‐G is a nontoxic, durable, and conductive biomaterial that is able to improve cardiac function for up to 1 year post‐implantation.
Arrhythmia is associated with blocked electrical conduction pathways stemming from myocardial fibrosis. A conductive biopolymer, poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin (PAMB‐G), restores electrical propagation in rat cardiac scar tissue. Its long‐term functionality and toxicity for potential therapeutic use is assessed. PAMB‐G demonstrates long‐term biocompatibility, arrhythmia reduction, along with electrical propagation and functional improvements, thereby providing a novel treatment for cardiac conduction abnormalities. |
doi_str_mv | 10.1002/adhm.202101838 |
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Arrhythmia is associated with blocked electrical conduction pathways stemming from myocardial fibrosis. A conductive biopolymer, poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin (PAMB‐G), restores electrical propagation in rat cardiac scar tissue. Its long‐term functionality and toxicity for potential therapeutic use is assessed. PAMB‐G demonstrates long‐term biocompatibility, arrhythmia reduction, along with electrical propagation and functional improvements, thereby providing a novel treatment for cardiac conduction abnormalities.</description><identifier>ISSN: 2192-2640</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.202101838</identifier><identifier>PMID: 34704404</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Acute toxicity ; Animals ; Arrhythmia ; Biocompatibility ; Biocompatible Materials - chemistry ; Biomaterials ; Biomedical materials ; Biopolymers ; Body weight ; Cardiac arrhythmia ; Cardiac function ; Cardiomyocytes ; Conducting polymers ; conductive biopolymers ; Congestive heart failure ; durability ; Electric Conductivity ; Electrical conduction ; Fibrosis ; Gelatin ; Injection ; Intravenous administration ; Mass spectrometry ; Mass spectroscopy ; Mice ; Myocardial infarction ; Myocardial Infarction - therapy ; Myocardium ; Myocardium - pathology ; Polymers - therapeutic use ; poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin ; Rats ; Reproductive organs ; Surgical implants ; Toxicity ; Ventricle</subject><ispartof>Advanced healthcare materials, 2022-01, Vol.11 (2), p.e2101838-n/a</ispartof><rights>2021 Wiley‐VCH GmbH</rights><rights>2021 Wiley-VCH GmbH.</rights><rights>2022 Wiley‐VCH GmbH</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3738-fa11bb8d80f580b97033a380d6f0b751e250a98a7eab3a5458ceccaa87cbd52a3</citedby><cites>FETCH-LOGICAL-c3738-fa11bb8d80f580b97033a380d6f0b751e250a98a7eab3a5458ceccaa87cbd52a3</cites><orcidid>0000-0002-2584-060X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadhm.202101838$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.202101838$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34704404$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fu, Anne</creatorcontrib><creatorcontrib>Yang, Yahan</creatorcontrib><creatorcontrib>Wu, Jun</creatorcontrib><creatorcontrib>Li, Shu‐Hong</creatorcontrib><creatorcontrib>Fan, Yunfei</creatorcontrib><creatorcontrib>Yau, Terrance M</creatorcontrib><creatorcontrib>Li, Ren‐Ke</creatorcontrib><title>Bio‐Conductive Polymers for Treating Myocardial Conductive Defects: Long‐Term Efficacy Study</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>Following myocardial infarction (MI), the resulting fibrotic scar is nonconductive and leads to ventricular dysfunction via electrical uncoupling of the remaining viable cardiomyocytes. The uneven conductive properties between normal myocardium and scar tissue result in arrhythmia, yielding sudden cardiac death/heart failure. A conductive biopolymer, poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin (PAMB‐G), is able to resynchronize myocardial contractions in vivo. Intravenous PAMB‐G injections into mice show that it does not cause any acute toxicity, up to the maximum tolerated dose (1.6 mL kg−1), which includes the determined therapeutic dose (0.4 mL kg−1). There is also no short‐ or long‐term toxicity when PAMB‐G is injected into the myocardium of MI rats, with no significant changes in body weight, organ–brain ratio, hematologic, and histological parameters for up to 12 months post‐injection. At the therapeutic dose, PAMB‐G restores electrical conduction in infarcted rat hearts, resulting in lowered arrhythmia susceptibility and improved cardiac function. PAMB‐G is also durable, as mass spectrometry detected the biopolymer for up to 12 months post‐injection. PAMB‐G did not impact reproductive organ function or offspring characteristics when given intravenously into healthy adult rats. Thus, PAMB‐G is a nontoxic, durable, and conductive biomaterial that is able to improve cardiac function for up to 1 year post‐implantation.
Arrhythmia is associated with blocked electrical conduction pathways stemming from myocardial fibrosis. A conductive biopolymer, poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin (PAMB‐G), restores electrical propagation in rat cardiac scar tissue. Its long‐term functionality and toxicity for potential therapeutic use is assessed. PAMB‐G demonstrates long‐term biocompatibility, arrhythmia reduction, along with electrical propagation and functional improvements, thereby providing a novel treatment for cardiac conduction abnormalities.</description><subject>Acute toxicity</subject><subject>Animals</subject><subject>Arrhythmia</subject><subject>Biocompatibility</subject><subject>Biocompatible Materials - chemistry</subject><subject>Biomaterials</subject><subject>Biomedical materials</subject><subject>Biopolymers</subject><subject>Body weight</subject><subject>Cardiac arrhythmia</subject><subject>Cardiac function</subject><subject>Cardiomyocytes</subject><subject>Conducting polymers</subject><subject>conductive biopolymers</subject><subject>Congestive heart failure</subject><subject>durability</subject><subject>Electric Conductivity</subject><subject>Electrical conduction</subject><subject>Fibrosis</subject><subject>Gelatin</subject><subject>Injection</subject><subject>Intravenous administration</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Mice</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - therapy</subject><subject>Myocardium</subject><subject>Myocardium - pathology</subject><subject>Polymers - therapeutic use</subject><subject>poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin</subject><subject>Rats</subject><subject>Reproductive organs</subject><subject>Surgical implants</subject><subject>Toxicity</subject><subject>Ventricle</subject><issn>2192-2640</issn><issn>2192-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkLtOwzAUQC0Eoqh0ZUSWmFuu7TwcttIWitQKJMocHMcuqZK42AkoG5_AN_IlpGopbHi5Hs49VzoInREYEAB6KdKXYkCBEiCc8QN0QklE-zTwo8P934MO6jm3gvYFPgk4OUYd5oXgeeCdoOfrzHx9fI5Mmdayyt4UfjB5UyjrsDYWL6wSVVYu8bwxUtg0Ezn-w46VVrJyV3hmymWrWShb4InWmRSywY9VnTan6EiL3KnebnbR081kMZr2Z_e3d6PhrC9ZyHhfC0KShKcctM8hiUJgTDAOaaAhCX2iqA8i4iJUImHC93wulZRC8FAmqU8F66KLrXdtzWutXBWvTG3L9mRMAwoRC1jotdRgS0lrnLNKx2ubFcI2MYF40zTeNI33TduF8522TgqV7vGfgi0QbYH3LFfNP7p4OJ7Of-Xf8ZeFFQ</recordid><startdate>20220101</startdate><enddate>20220101</enddate><creator>Fu, Anne</creator><creator>Yang, Yahan</creator><creator>Wu, Jun</creator><creator>Li, Shu‐Hong</creator><creator>Fan, Yunfei</creator><creator>Yau, Terrance M</creator><creator>Li, Ren‐Ke</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QP</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T5</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7TO</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><orcidid>https://orcid.org/0000-0002-2584-060X</orcidid></search><sort><creationdate>20220101</creationdate><title>Bio‐Conductive Polymers for Treating Myocardial Conductive Defects: Long‐Term Efficacy Study</title><author>Fu, Anne ; 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The uneven conductive properties between normal myocardium and scar tissue result in arrhythmia, yielding sudden cardiac death/heart failure. A conductive biopolymer, poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin (PAMB‐G), is able to resynchronize myocardial contractions in vivo. Intravenous PAMB‐G injections into mice show that it does not cause any acute toxicity, up to the maximum tolerated dose (1.6 mL kg−1), which includes the determined therapeutic dose (0.4 mL kg−1). There is also no short‐ or long‐term toxicity when PAMB‐G is injected into the myocardium of MI rats, with no significant changes in body weight, organ–brain ratio, hematologic, and histological parameters for up to 12 months post‐injection. At the therapeutic dose, PAMB‐G restores electrical conduction in infarcted rat hearts, resulting in lowered arrhythmia susceptibility and improved cardiac function. PAMB‐G is also durable, as mass spectrometry detected the biopolymer for up to 12 months post‐injection. PAMB‐G did not impact reproductive organ function or offspring characteristics when given intravenously into healthy adult rats. Thus, PAMB‐G is a nontoxic, durable, and conductive biomaterial that is able to improve cardiac function for up to 1 year post‐implantation.
Arrhythmia is associated with blocked electrical conduction pathways stemming from myocardial fibrosis. A conductive biopolymer, poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin (PAMB‐G), restores electrical propagation in rat cardiac scar tissue. Its long‐term functionality and toxicity for potential therapeutic use is assessed. PAMB‐G demonstrates long‐term biocompatibility, arrhythmia reduction, along with electrical propagation and functional improvements, thereby providing a novel treatment for cardiac conduction abnormalities.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34704404</pmid><doi>10.1002/adhm.202101838</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-2584-060X</orcidid></addata></record> |
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subjects | Acute toxicity Animals Arrhythmia Biocompatibility Biocompatible Materials - chemistry Biomaterials Biomedical materials Biopolymers Body weight Cardiac arrhythmia Cardiac function Cardiomyocytes Conducting polymers conductive biopolymers Congestive heart failure durability Electric Conductivity Electrical conduction Fibrosis Gelatin Injection Intravenous administration Mass spectrometry Mass spectroscopy Mice Myocardial infarction Myocardial Infarction - therapy Myocardium Myocardium - pathology Polymers - therapeutic use poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin Rats Reproductive organs Surgical implants Toxicity Ventricle |
title | Bio‐Conductive Polymers for Treating Myocardial Conductive Defects: Long‐Term Efficacy Study |
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