Title: Cytotoxicity and biocompatibility evaluation of chitosan-beta glycerol phosphate-hydroxyethyl cellulose hydrogel on adult rat liver for cell-based therapeutic applications

Authors: Aliakber Haddad-Mashadrizeh; Maryam M. Matin; Ahmad Reza Bahrami; Mohammad Amin Edalatmanesh; Hojjat Naderi-Meshkin; Sara Mousavi; Mossa Gardaneh

Addresses: Cell and Molecular Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran ' Cell and Molecular Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran ' Cell and Molecular Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran ' Department of Physiology, Science & Research Branch, Islamic Azad University, Fars, Iran ' Cell and Molecular Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran; Stem Cell and Regenerative Medicine Research Department, Iranian Academic Center for Education, Culture and Research (ACECR), Mashhad Branch, Mashhad, Iran ' Cell and Molecular Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran ' National Institute for Genetic Engineering and Biotechnology, Tehran, Iran

Abstract: The pace of developing cell-based therapeutic systems by application of cellular scaffolds has been steady though slow. In present study, a chitosan based scaffold, CH-β-GP-HEC, was implanted into the rat liver to evaluate its biocompatibility, and particularly to test its cytotoxic effects during six months after implantation. The injected rats showed no obvious inflammatory responses during examination. Histological analyses revealed no difference between sections of the livers of test, vehicle and control groups after implantation, except regions which were occupied by injected scaffolds in the test group. The microscopic observations revealed that the size of the implanted scaffolds decreased by time. Moreover, analysing liver function based on the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as biomarkers of liver injury, showed a significant increase in the first two weeks after implantation. This rate however, returned to normal level gradually. This reduction of the scaffold size along with the gradual reduction of the injury markers are signs of biodegradability and biocompatibility of the scaffold which make it a suitable candidate in cell based therapeutic programmes.

Keywords: AST; aspartate aminotransferase; ALT; alanine aminotransferase; CH-β-GP-HEC; biocompatibility; cytotoxicity; chitosan beta glycerol phosphate hydroxyethyl; cellulose hydrogels; adult rat livers; cell-based therapeutic systems; cellular scaffolds; inflammatory response; biomarkers; liver injury; scaffold size; biomaterials; cell migration; tissue engineering; cell confinement; transplant sites; stem cells; cell therapy; liver disease.

DOI: 10.1504/IJBET.2013.057260

International Journal of Biomedical Engineering and Technology, 2013 Vol.12 No.3, pp.228 - 239

Received: 05 Dec 2012
Accepted: 26 Jul 2013

Published online: 27 Sep 2014 *

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