Chitosan-Polyethylene Glycol Inspired Polyelectrolyte Complex Hydrogel Templates Favoring NEO-Tissue Formation for Cardiac Tissue Engineering

Overview

Journal Gels

Date 2024 Jan 22

PMID 38247769

Authors

Angelo Keklikian

Natan Roberto de Barros

Ahmad Rashad

Yiqing Chen

Jinrui Tan

Ruoyu Sheng

Dongwei Sun

Huinan Liu

Finosh G Thankam

Affiliations

Soon will be listed here.

Abstract

Neo-tissue formation and host tissue regeneration determine the success of cardiac tissue engineering where functional hydrogel scaffolds act as cardiac (extracellular matrix) ECM mimic. Translationally, the hydrogel templates promoting neo-cardiac tissue formation are currently limited; however, they are highly demanding in cardiac tissue engineering. The current study focused on the development of a panel of four chitosan-based polyelectrolyte hydrogels as cardiac scaffolds facilitating neo-cardiac tissue formation to promote cardiac regeneration. Chitosan-PEG (CP), gelatin-chitosan-PEG (GCP), hyaluronic acid-chitosan-PEG (HACP), and combined CP (CoCP) polyelectrolyte hydrogels were engineered by solvent casting and assessed for physiochemical, thermal, electrical, biodegradable, mechanical, and biological properties. The CP, GCP, HACP, and CoCP hydrogels exhibited excellent porosity (4.24 ± 0.18, 13.089 ± 1.13, 12.53 ± 1.30 and 15.88 ± 1.10 for CP, GCP, HACP and CoCP, respectively), water profile, mechanical strength, and amphiphilicity suitable for cardiac tissue engineering. The hydrogels were hemocompatible as evident from the negligible hemolysis and RBC aggregation and increased adsorption of plasma albumin. The hydrogels were cytocompatible as evident from the increased viability by MTT (>94% for all the four hydrogels) assay and direct contact assay. Also, the hydrogels supported the adhesion, growth, spreading, and proliferation of H9c2 cells as unveiled by rhodamine staining. The hydrogels promoted neo-tissue formation that was proven using rat and swine myocardial tissue explant culture. Compared to GCP and CoCP, CP and HACP were superior owing to the cell viability, hemocompatibility, and conductance, resulting in the highest degree of cytoskeletal organization and neo-tissue formation. The physiochemical and biological performance of these hydrogels supported neo-cardiac tissue formation. Overall, the CP, GCP, HACP, and CoCP hydrogel systems promise novel translational opportunities in regenerative cardiology.

References

Sharifisistani M, Khanmohammadi M, Badali E, Ghasemi P, Hassanzadeh S, Bahiraie N . Hyaluronic acid/gelatin microcapsule functionalized with carbon nanotube through laccase-catalyzed crosslinking for fabrication of cardiac microtissue. J Biomed Mater Res A. 2022; 110(12):1866-1880. DOI: 10.1002/jbm.a.37419. View

Nuttelman C, Henry S, Anseth K . Synthesis and characterization of photocrosslinkable, degradable poly(vinyl alcohol)-based tissue engineering scaffolds. Biomaterials. 2002; 23(17):3617-26. DOI: 10.1016/s0142-9612(02)00093-5. View

Jiang L, Chen D, Wang Z, Zhang Z, Xia Y, Xue H . Preparation of an Electrically Conductive Graphene Oxide/Chitosan Scaffold for Cardiac Tissue Engineering. Appl Biochem Biotechnol. 2019; 188(4):952-964. DOI: 10.1007/s12010-019-02967-6. View

Chow A, Stuckey D, Kidher E, Rocco M, Jabbour R, Mansfield C . Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction. Stem Cell Reports. 2017; 9(5):1415-1422. PMC: 5830963. DOI: 10.1016/j.stemcr.2017.09.003. View

Si R, Gao C, Guo R, Lin C, Li J, Guo W . Human mesenchymal stem cells encapsulated-coacervated photoluminescent nanodots layered bioactive chitosan/collagen hydrogel matrices to indorse cardiac healing after acute myocardial infarction. J Photochem Photobiol B. 2020; 206:111789. DOI: 10.1016/j.jphotobiol.2020.111789. View

Li Z, Masumoto H, Jo J, Yamazaki K, Ikeda T, Tabata Y . Sustained release of basic fibroblast growth factor using gelatin hydrogel improved left ventricular function through the alteration of collagen subtype in a rat chronic myocardial infarction model. Gen Thorac Cardiovasc Surg. 2018; 66(11):641-647. DOI: 10.1007/s11748-018-0969-z. View

Li J, Shu Y, Hao T, Wang Y, Qian Y, Duan C . A chitosan-glutathione based injectable hydrogel for suppression of oxidative stress damage in cardiomyocytes. Biomaterials. 2013; 34(36):9071-81. DOI: 10.1016/j.biomaterials.2013.08.031. View

Vogler E . Water and the acute biological response to surfaces. J Biomater Sci Polym Ed. 1999; 10(10):1015-45. DOI: 10.1163/156856299x00667. View

Chang C, Chan A, Armstrong P, Luo H, Higuchi T, Strehin I . Hyaluronic acid-human blood hydrogels for stem cell transplantation. Biomaterials. 2012; 33(32):8026-33. PMC: 3432174. DOI: 10.1016/j.biomaterials.2012.07.058. View

10.

Zhang F, Zhang N, Meng H, Liu H, Lu Y, Liu C . Easy Applied Gelatin-Based Hydrogel System for Long-Term Functional Cardiomyocyte Culture and Myocardium Formation. ACS Biomater Sci Eng. 2021; 5(6):3022-3031. DOI: 10.1021/acsbiomaterials.9b00515. View

11.

Sedighim S, Chen Y, Xu C, Mohindra R, Liu H, Agrawal D . Carboxymethyl cellulose-alginate interpenetrating hydroxy ethyl methacrylate crosslinked polyvinyl alcohol reinforced hybrid hydrogel templates with improved biological performance for cardiac tissue engineering. Biotechnol Bioeng. 2022; 120(3):819-835. PMC: 9931685. DOI: 10.1002/bit.28291. View

12.

Dobner S, Bezuidenhout D, Govender P, Zilla P, Davies N . A synthetic non-degradable polyethylene glycol hydrogel retards adverse post-infarct left ventricular remodeling. J Card Fail. 2009; 15(7):629-36. DOI: 10.1016/j.cardfail.2009.03.003. View

13.

Beleno Acosta B, Advincula R, Grande-Tovar C . Chitosan-Based Scaffolds for the Treatment of Myocardial Infarction: A Systematic Review. Molecules. 2023; 28(4). PMC: 9962426. DOI: 10.3390/molecules28041920. View

14.

Basara G, Gulberk Ozcebe S, Ellis B, Zorlutuna P . Tunable Human Myocardium Derived Decellularized Extracellular Matrix for 3D Bioprinting and Cardiac Tissue Engineering. Gels. 2021; 7(2). PMC: 8293197. DOI: 10.3390/gels7020070. View

15.

Thankam F, Muthu J . Alginate-polyester comacromer based hydrogels as physiochemically and biologically favorable entities for cardiac tissue engineering. J Colloid Interface Sci. 2015; 457:52-61. DOI: 10.1016/j.jcis.2015.06.034. View

16.

Ifkovits J, Tous E, Minakawa M, Morita M, Robb J, Koomalsingh K . Injectable hydrogel properties influence infarct expansion and extent of postinfarction left ventricular remodeling in an ovine model. Proc Natl Acad Sci U S A. 2010; 107(25):11507-12. PMC: 2895138. DOI: 10.1073/pnas.1004097107. View

17.

de Oliveira A, Sabino R, Souza P, Muniz E, Popat K, Kipper M . Chitosan/gellan gum ratio content into blends modulates the scaffolding capacity of hydrogels on bone mesenchymal stem cells. Mater Sci Eng C Mater Biol Appl. 2019; 106:110258. DOI: 10.1016/j.msec.2019.110258. View

18.

Aswathy S, NarendraKumar U, Manjubala I . Commercial hydrogels for biomedical applications. Heliyon. 2020; 6(4):e03719. PMC: 7138915. DOI: 10.1016/j.heliyon.2020.e03719. View

19.

Hao Y, Zhao W, Zhang H, Zheng W, Zhou Q . Carboxymethyl chitosan-based hydrogels containing fibroblast growth factors for triggering diabetic wound healing. Carbohydr Polym. 2022; 287:119336. DOI: 10.1016/j.carbpol.2022.119336. View

20.

Deng B, Shen L, Wu Y, Shen Y, Ding X, Lu S . Delivery of alginate-chitosan hydrogel promotes endogenous repair and preserves cardiac function in rats with myocardial infarction. J Biomed Mater Res A. 2014; 103(3):907-18. DOI: 10.1002/jbm.a.35232. View