TY - JOUR
T1 - Gold nanorod-incorporated gelatin-based conductive hydrogels for engineering cardiac tissue constructs
AU - Navaei, Ali
AU - Saini, Harpinder
AU - Christenson, Wayne
AU - Sullivan, Ryan Tanner
AU - Ros, Robert
AU - Nikkhah, Mehdi
N1 - Funding Information:
The monoclonal antibody, TI-4, developed by Stefano Schiaffino was purchased from the Developmental studies Hybridoma Bank, created by NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. We gratefully acknowledge the use of facilities with the LeRoy Eyring Center for Solid State Science at Arizona State University. We acknowledge N. Chamele for helping for impedance analyzing, and Bryant Doss for the development of the AFM analysis programs. This work was partially supported by National Institute of Health (NIH) grants HL107539 and U54CA143862 to Robert Ros.
Funding Information:
The monoclonal antibody, TI-4, developed by Stefano Schiaffino was purchased from the Developmental studies Hybridoma Bank, created by NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. We gratefully acknowledge the use of facilities with the LeRoy Eyring Center for Solid State Science at Arizona State University. We acknowledge N. Chamele for helping for impedance analyzing, and Bryant Doss for the development of the AFM analysis programs. This work was partially supported by National Institute of Health ( NIH ) grants HL107539 and U54CA143862 to Robert Ros.
Publisher Copyright:
© 2016 Acta Materialia Inc.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - The development of advanced biomaterials is a crucial step to enhance the efficacy of tissue engineering strategies for treatment of myocardial infarction. Specific characteristics of biomaterials including electrical conductivity, mechanical robustness and structural integrity need to be further enhanced to promote the functionalities of cardiac cells. In this work, we fabricated UV-crosslinkable gold nanorod (GNR)-incorporated gelatin methacrylate (GelMA) hybrid hydrogels with enhanced material and biological properties for cardiac tissue engineering. Embedded GNRs promoted electrical conductivity and mechanical stiffness of the hydrogel matrix. Cardiomyocytes seeded on GelMA-GNR hybrid hydrogels exhibited excellent cell retention, viability, and metabolic activity. The increased cell adhesion resulted in abundance of locally organized F-actin fibers, leading to the formation of an integrated tissue layer on the GNR-embedded hydrogels. Immunostained images of integrin β-1 confirmed improved cell-matrix interaction on the hybrid hydrogels. Notably, homogeneous distribution of cardiac specific markers (sarcomeric α-actinin and connexin 43), were observed on GelMA-GNR hydrogels as a function of GNRs concentration. Furthermore, the GelMA-GNR hybrids supported synchronous tissue-level beating of cardiomyocytes. Similar observations were also noted by, calcium transient assay that demonstrated the rhythmic contraction of the cardiomyocytes on GelMA-GNR hydrogels as compared to pure GelMA. Thus, the findings of this study clearly demonstrated that functional cardiac patches with superior electrical and mechanical properties can be developed using nanoengineered GelMA-GNR hybrid hydrogels. Statement of Significance In this work, we developed gold nanorod (GNR) incorporated gelatin-based hydrogels with suitable electrical conductivity and mechanical stiffness for engineering functional cardiac tissue constructs (e.g. cardiac patches). The synthesized conductive hybrid hydrogels properly accommodated cardiac cells and subsequently resulted in excellent cell retention, spreading, homogeneous distribution of cardiac specific markers, cell-cell coupling as well as robust synchronized (tissue-level) beating behavior.
AB - The development of advanced biomaterials is a crucial step to enhance the efficacy of tissue engineering strategies for treatment of myocardial infarction. Specific characteristics of biomaterials including electrical conductivity, mechanical robustness and structural integrity need to be further enhanced to promote the functionalities of cardiac cells. In this work, we fabricated UV-crosslinkable gold nanorod (GNR)-incorporated gelatin methacrylate (GelMA) hybrid hydrogels with enhanced material and biological properties for cardiac tissue engineering. Embedded GNRs promoted electrical conductivity and mechanical stiffness of the hydrogel matrix. Cardiomyocytes seeded on GelMA-GNR hybrid hydrogels exhibited excellent cell retention, viability, and metabolic activity. The increased cell adhesion resulted in abundance of locally organized F-actin fibers, leading to the formation of an integrated tissue layer on the GNR-embedded hydrogels. Immunostained images of integrin β-1 confirmed improved cell-matrix interaction on the hybrid hydrogels. Notably, homogeneous distribution of cardiac specific markers (sarcomeric α-actinin and connexin 43), were observed on GelMA-GNR hydrogels as a function of GNRs concentration. Furthermore, the GelMA-GNR hybrids supported synchronous tissue-level beating of cardiomyocytes. Similar observations were also noted by, calcium transient assay that demonstrated the rhythmic contraction of the cardiomyocytes on GelMA-GNR hydrogels as compared to pure GelMA. Thus, the findings of this study clearly demonstrated that functional cardiac patches with superior electrical and mechanical properties can be developed using nanoengineered GelMA-GNR hybrid hydrogels. Statement of Significance In this work, we developed gold nanorod (GNR) incorporated gelatin-based hydrogels with suitable electrical conductivity and mechanical stiffness for engineering functional cardiac tissue constructs (e.g. cardiac patches). The synthesized conductive hybrid hydrogels properly accommodated cardiac cells and subsequently resulted in excellent cell retention, spreading, homogeneous distribution of cardiac specific markers, cell-cell coupling as well as robust synchronized (tissue-level) beating behavior.
KW - Calcium puffs
KW - Cardiac patches
KW - Conductive hydrogels
KW - Gelatin methacrylate
KW - Myocardial infarction
KW - Synchronous beating
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U2 - 10.1016/j.actbio.2016.05.027
DO - 10.1016/j.actbio.2016.05.027
M3 - Article
C2 - 27212425
AN - SCOPUS:84973549978
SN - 1742-7061
VL - 41
SP - 133
EP - 146
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -