title: Gold nanorod-incorporated gelatin-based conductive hydrogels for engineering cardiac tissue constructs.
abstract: 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.
  
  
  
  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.
authors.affiliation: School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Navaei
authors.affiliation: School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Harpinder
authors.initials: H
authors.lastname: Saini
authors.affiliation: Department of Physics, Arizona State University, Tempe, AZ 85287, USA; Center for Biological Physics, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Christenson
authors.affiliation: School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Ryan Tanner
authors.initials: RT
authors.lastname: Sullivan
authors.affiliation: Department of Physics, Arizona State University, Tempe, AZ 85287, USA; Center for Biological Physics, Arizona State University, Tempe, AZ 85287, USA; Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ros
authors.affiliation: School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ 85287, USA. Electronic address: mnikkhah@asu.edu.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nikkhah
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D021982:Cell-Matrix Junctions / Q000187:drug effects / Q000378:metabolism; D004553:Electric Conductivity; D004558:Electric Stimulation; D005780:Gelatin / Q000494:pharmacology*; D006046:Gold / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D020100:Hydrogels / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D043942:Nanotubes / Q000737:chemistry*; D009928:Organ Specificity / Q000187:drug effects; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D020100:Hydrogels; D006046:Gold; D005780:Gelatin; D002118:Calcium
keywords: Calcium(2+) puffs; Cardiac patches; Conductive hydrogels; Gelatin methacrylate; Myocardial infarction; Synchronous beating