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Hyaluronic Acid/Gelatin Microcapsule Functionalized With Carbon Nanotube Through Laccase-Catalyzed Crosslinking for Fabrication of Cardiac Microtissue Publisher Pubmed



Sharifisistani M1 ; Khanmohammadi M2 ; Badali E2, 3 ; Ghasemi P4, 5 ; Hassanzadeh S2 ; Bahiraie N6 ; Lotfibakhshaiesh N1 ; Ai J1
Authors
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Authors Affiliations
  1. 1. Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Skull Base Research Center, The Five Senses Institute, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
  3. 3. Chemistry Department, Kharazmi University, Tehran, Iran
  4. 4. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran
  5. 5. Department of Nanotechnology, Faculty of Chemistry, University of Isfahan, Isfahan, Iran
  6. 6. Tissue Engineering and Applied Cell Sciences Division, Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Source: Journal of Biomedical Materials Research - Part A Published:2022


Abstract

Carbon nanotube (CNT) and gelatin (Gela) molecules are effective substrates in promoting engineered cardiac tissue functions. This study developed a microfluidic-based encapsulation process for biomimetic hydrogel microcapsule fabrication. The hydrogel microcapsule was produced through a coaxial double orifice microfluidic technique and a water-in-oil emulsion system in two sequential processes. The phenol (Ph) substituted Gela (Gela-Ph) and CNT (CNT-Ph), respectively as cell-adhesive and electrically conductive substrates were incorporated in hyaluronic acid (HA)-based hydrogel through laccase-mediated crosslinking. The Cardiomyocyte-enclosing microcapsule fabricated and cellular survival, function, and possible difference in the biological activity of encapsulated cells within micro vehicles were investigated. The coaxial microfluidic method and Lac-mediated crosslinking reaction resulted in spherical vehicle production in 183 μm diameter at 500 capsules/min speed. The encapsulation process did not affect cellular viability and harvested cells from microcapsule proliferated well likewise subcultured cells in tissue culture plate. The biophysical properties of the designed hydrogel, including mechanical strength, swelling, biodegradability and electroconductivity upregulated significantly for hydrogels decorated covalently with Gela-Ph and CNT-Ph. The tendency of the microcapsule for the spheroid formation of cardiomyocytes inside the proposed microcapsule occurred 3 days after encapsulation. Interestingly, immobilized Gela-Ph and CNT-Ph promote cellular growth and specific cardiac markers. Overall, the microfluidic-based encapsulation technology and synthesized biomimetic substrates with electroconductive properties demonstrate desirable cellular adhesion, proliferation, and cardiac functions for engineering cardiac tissue. © 2022 Wiley Periodicals LLC.
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