Eshan Sayani

Background: Myocardial infarction (MI) is a common condition that can lead to cardiac fibrosis and heart failure^1,2,3,4,5,6. Current treatments have limitations in targeting fibrotic tissue and there are no reliable biomarkers to predict the development or severity of fibrosis^1,2,3. The lack of effective treatments for established post-MI cardiac fibrosis further underscores the need for new therapies^1,2,3.

Objective: This review aims to summarize recent research on new biomaterials and therapies for cardiac tissue regeneration and restoration of normal heart function following MI.

Search Methods: An online search in the PubMed database was conducted from 2018 to 2023 using the following keywords: “conductive biomaterials”, “cardiac fibrosis”, “conductive hydrogels”.

Results: Several studies have addressed challenges in cardiac tissue regeneration by developing electroconductive scaffolds, cardiopatches, and conductive hydrogels^7,8,9,10,11. The electroconductive scaffolds combine biocompatible and conductive polymers and promote cell adhesion, proliferation, and spreading without cytotoxicity⁷. The resulting biomimetic scaffolds have potential as implantable biomaterials for cardiac tissue regeneration and as 3D tissue models for biomolecule screening⁷. Cardiopatches were also developed by electrospinning gelatin methacryloyl (GelMA) and conjugating a choline-based bio-ionic liquid (Bio-IL), which exhibited mechanical and conductive properties similar to native myocardium and improved contractile profiles compared to pristine GelMA controls⁸. Additionally, the conductive hydrogel, PPY-CHI, was investigated to improve electrical propagation in fibrotic cardiac tissue and resynchronize cardiac contraction to preserve cardiac function⁹. PPY-CHI hydrogel increased conductivity and reduced tissue resistance, leading to improved electrical conduction across the fibrotic scar, enhanced field potential amplitudes, and resynchronized cardiac contraction⁹. Furthermore, An injectable conductive hydrogel loaded with plasmid DNA and adipose-derived stem cells improved heart function and increased vessel density in rats with myocardial infarction¹⁰. Finally, an auxetic conductive cardiac patch for the treatment of myocardial infarction that is cytocompatible with cardiomyocytes, conforms to native heart movements, and in vivo experiments show negligible fibrotic response after two weeks, making it a versatile and robust platform for cardiac biomaterial design and a promising treatment option¹¹.

Conclusions: Cardiac fibrosis is a pathological condition that manifests as the accumulation of extracellular matrix proteins in cardiac tissue, resulting in the formation of scars that disrupt normal tissue architecture^1,2. These scars may function as electrical barriers, leading to arrhythmias and heart failure^1,2. Conductive biomaterials have shown potential for restoring cardiac function by improving electrical propagation across fibrotic scars^{3,7,8,9,10,11}. However, further research is required to optimize the mechanical and electrical properties of conductive biomaterials in vivo, as well as to investigate strategies to promote vascular regeneration, in order to develop a more viable treatment option for human patients^{3,7,8,9,10,11}.

Works Cited:

1. Frangogiannis NG. Cardiac fibrosis. Cardiovasc Res. 2021;117(6):1450-1488. doi:10.1093/cvr/cvaa324
2. Czubryt MP, Hale TM. Cardiac fibrosis: Pathobiology and therapeutic targets. Cell Signal. 2021;85:110066. doi:10.1016/j.cellsig.2021.110066
3. Li Y, Wei L, Lan L, et al. Conductive biomaterials for cardiac repair: A review. Acta Biomater. 2022;139:157-178. doi:10.1016/j.actbio.2021.04.018
4. Morsink M, Severino P, Luna-Ceron E, Hussain MA, Sobahi N, Shin SR. Effects of electrically conductive nano-biomaterials on regulating cardiomyocyte behavior for cardiac repair and regeneration. Acta Biomater. 2022;139:141-156. doi:10.1016/j.actbio.2021.11.022
5. Saleh M, Ambrose JA. Understanding myocardial infarction. F1000Res. 2018;7:F1000 Faculty Rev-1378. Published 2018 Sep 3. doi:10.12688/f1000research.15096.1
6. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018;72(18):2231-2264. doi:10.1016/j.jacc.2018.08.1038
7. Furlani F, Campodoni E, Sangiorgi N, et al. Electroconductive scaffolds based on gelatin and PEDOT:PSS for cardiac regeneration. International Journal of Biological Macromolecules. 2023;224:266-280. doi:10.1016/j.ijbiomac.2022.10.122
8. Walker BW, Lara RP, Yu CH, et al. Engineering a naturally-derived adhesive and conductive cardiopatch. Biomaterials. 2019;207:89-101. doi:10.1016/j.biomaterials.2019.03.015
9. He S, Wu J, Li SH, et al. The conductive function of biopolymer corrects myocardial scar conduction blockage and resynchronizes contraction to prevent heart failure. Biomaterials. 2020;258. doi:10.1016/j.biomaterials.2020.120285
10. Wang W, Tan B, Chen J, et al. An injectable conductive hydrogel encapsulating plasmid DNA-eNOs and ADSCs for treating myocardial infarction. Biomaterials. 2018;16:69-81. doi:10.1018/j.biomaterials.2018.01.021
11. Kapnisi M, Mansfield C, Marijon C, et al. Auxetic cardiac patches with tunable mechanical and conductive properties toward treating myocardial infarction. Advanced Functional Materials. 2018;28(21):1800618. doi:10.1002/adfm.201800618