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Nanoparticle-Based Hybrid Scaffolds for Deciphering the Role of Multimodal Cues in Cardiac Tissue Engineering.

ABSTRACT: Myocardial microenvironment plays a decisive role in guiding the function and fate of cardiomyocytes, and engineering this extracellular niche holds great promise for cardiac tissue regeneration. Platforms utilizing hybrid hydrogels containing various types of conductive nanoparticles have been a critical tool for constructing engineered cardiac tissues with outstanding mechanical integrity and improved electrophysiological properties. However, there has been no attempt to directly compare the efficacy of these hybrid hydrogels and decipher the mechanisms behind how these platforms differentially regulate cardiomyocyte behavior. Here, we employed gelatin methacryloyl (GelMA) hydrogels containing three different types of carbon-based nanoparticles: carbon nanotubes (CNTs), graphene oxide (GO), and reduced GO (rGO), to investigate the influence of these hybrid scaffolds on the structural organization and functionality of cardiomyocytes. Using immunofluorescent staining for assessing cellular organization and proliferation, we showed that electrically conductive scaffolds (CNT- and rGO-GelMA compared to relatively nonconductive GO-GelMA) played a significant role in promoting desirable morphology of cardiomyocytes and elevated the expression of functional cardiac markers, while maintaining their viability. Electrophysiological analysis revealed that these engineered cardiac tissues showed distinct cardiomyocyte phenotypes and different levels of maturity based on the substrate (CNT-GelMA: ventricular-like, GO-GelMA: atrial-like, and rGO-GelMA: ventricular/atrial mixed phenotypes). Through analysis of gene-expression patterns, we uncovered that the engineered cardiac tissues matured on CNT-GelMA and native cardiac tissues showed comparable expression levels of maturation markers. Furthermore, we demonstrated that engineered cardiac tissues matured on CNT-GelMA have increased functionality through integrin-mediated mechanotransduction (via YAP/TAZ) in contrast to cardiomyocytes cultured on rGO-GelMA.

SUBMITTER: Lee J

PROVIDER: S-EPMC7068777 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Nanoparticle-Based Hybrid Scaffolds for Deciphering the Role of Multimodal Cues in Cardiac Tissue Engineering.

Lee Junmin J Manoharan Vijayan V Cheung Louis L Lee Seungkyu S Cha Byung-Hyun BH Newman Peter P Farzad Razieh R Mehrotra Shreya S Zhang Kaizhen K Khan Fazal F Ghaderi Masoumeh M Lin Yi-Dong YD Aftab Saira S Mostafalu Pooria P Miscuglio Mario M Li Joan J Mandal Biman B BB Hussain Mohammad Asif MA Wan Kai-Tak KT Tang Xiaowu Shirley XS Khademhosseini Ali A Shin Su Ryon SR

ACS nano 20191028 11

Myocardial microenvironment plays a decisive role in guiding the function and fate of cardiomyocytes, and engineering this extracellular niche holds great promise for cardiac tissue regeneration. Platforms utilizing hybrid hydrogels containing various types of conductive nanoparticles have been a critical tool for constructing engineered cardiac tissues with outstanding mechanical integrity and improved electrophysiological properties. However, there has been no attempt to directly compare the e ...[more]

PMID: 31621284

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Project description:Myocardial infarction (MI) causes significant cell loss and damage to myocardium. Cell-based therapies for treatment of MI aim to remuscularize the resultant scar tissue, but the majority of transplanted cells do not survive or integrate with the host tissue. Scaffolds can improve cell retention following construct implantation, but often do little to enhance host-graft integration and/or show limited biodegradation. Fibrin is an ideal biomaterial for cardiac tissue engineering as it is a natural, biodegradable polymer that can induce neovascularization, promote cell attachment, and has tunable mechanical properties. Here we describe a novel, high-density microtemplated fibrin scaffold seeded with a tri-cell mixture of cardiomyocytes, endothelial cells (ECs), and fibroblasts to mimic native cardiac tissue in structure and cellular composition to improve cell retention and promote integration with the host tissue. Scaffolds were designed with uniform architecture of parallel 60 ?m microchannels surrounded by an interconnected microporous network of 27-?m-diameter pores and mechanical stiffness comparable to native cardiac tissues (70-90kPa). Scaffold degradation was controlled with the addition of Factor XIII (FXIII) and/or protease inhibitor (aprotinin). Unmodified scaffolds had a fast degradation profile both in vitro (19.9%±3.9% stiffness retention after 10 days) and in vivo. Scaffolds treated with FXIII showed an intermediate degradation profile in vitro (45.8%±5.9%), while scaffolds treated with aprotinin or both FXIII and aprotinin showed significantly slowed degradation in vitro (60.9%±5.2% and 76.4%±7.6%, respectively, p<0.05). Acellular aprotinin scaffold myocardial implants showed decreased collagen deposition after 7 days. Unmodified and aprotinin implants could not be located by 14 days, while 2 of 8 FXIII implants were found, but were significantly degraded. Constructs supported seeded cell survival and organization in vitro, promoting EC-lined lumen structure formation in construct channels and colocalization of viable ECs and cardiomyocytes. In addition, constructs promoted extracellular matrix deposition by seeded cells, as shown by collagen staining within construct channels and by significant increases in construct stiffness over 10 days in vitro (209%±32%, p<0.05). The data suggest our fibrin scaffolds are ideally designed to promote graft cell survival and organization, thus improving chances of promoting construct integration with the host tissue upon implantation.

Dataset Information

Nanoparticle-Based Hybrid Scaffolds for Deciphering the Role of Multimodal Cues in Cardiac Tissue Engineering.

Publications

Nanoparticle-Based Hybrid Scaffolds for Deciphering the Role of Multimodal Cues in Cardiac Tissue Engineering.

Similar Datasets

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