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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Veröffentlicht in:Advanced healthcare materials 2022-01, Vol.11 (2), p.e2101838-n/a
Hauptverfasser: Fu, Anne, Yang, Yahan, Wu, Jun, Li, Shu‐Hong, Fan, Yunfei, Yau, Terrance M, Li, Ren‐Ke
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container_issue 2
container_start_page e2101838
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creator Fu, Anne
Yang, Yahan
Wu, Jun
Li, Shu‐Hong
Fan, Yunfei
Yau, Terrance M
Li, Ren‐Ke
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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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. 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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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