Thermosensitive Hydrogel Development for Its Possible Application in Cardiac Cell Therapy

Authors: Lina Paola Orozco-Marín, Yuliet Montoya, John Bustamante

Abstract:

Ischemic events can culminate in acute myocardial infarction with irreversible cardiac lesions that cannot be restored due to the limited regenerative capacity of the heart. Tissue engineering proposes therapeutic alternatives by using biomaterials to resemble the native extracellular medium combined with healthy and functional cells. This research focused on developing a natural thermosensitive hydrogel, its physical-chemical characterization and in vitro biocompatibility determination. Hydrogels’ morphological characterization was carried out through scanning electron microscopy and its chemical characterization by employing Infrared Spectroscopy technic. In addition, the biocompatibility was determined using fetal human ventricular cardiomyocytes cell line RL-14 and the MTT cytotoxicity test according to the ISO 10993-5 standard. Four biocompatible and thermosensitive hydrogels were obtained with a three-dimensional internal structure and two gelation times. The results show the potential of the hydrogel to increase the cell survival rate to the cardiac cell therapies under investigation and lay the foundations to continue with its characterization and biological evaluation both in vitro and in vivo models.

Keywords: cardiac cell therapy, cardiac ischemia, natural polymers, thermosensitive hydrogel

References:

[1] WHO, “World Healt Organization (WHO),” 2017.
[Online]. Available: https://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).
[2] L. A. Lara-Martínez, I. Gutiérrez-Villegas, V. M. Arenas-Luna, and S. Hernández-Gutierrez, “Células madre: buscando marcadores de superficie celular que predispongan compromiso de diferenciación cardiaca,” Arch. Cardiol. México, vol. 88, no. 5, pp. 483–495, 2018.
[3] D. V. Gutiérrez Triana and P. Caro, “proceso de participacion para la promoción de la salud y la prevención de la enfermedad: La experiencia de la Dirección de Promoción y Prevención.,” Bogotá D.C, 2016.
[4] R. Sun, X. Li, M. Liu, Y. Zeng, S. Chen, and P. Zhang, “Advances in stem cell therapy for cardiovascular disease (Review),” Int. J. Mol. Med., vol. 38, no. 1, pp. 23–29, 2016.
[5] T. Eschenhagen et al., “Cardi
[omyocyte Regeneration: A Consensus Statement,” Circulation, vol. 136, no. 7, pp. 680–686, 2017.
[6] X. Tang et al., Polymeric Biomaterials in Tissue Engineering and Regenerative Medicine. Elsevier Inc., 2014.
[7] M. C. Catoira, L. Fusaro, D. Di Francesco, M. Ramella, and F. Boccafoschi, “Overview of natural hydrogels for regenerative medicine applications,” J. Mater. Sci. Mater. Med., vol. 30, no. 10, 2019.
[8] Q. Dang et al., “Fabrication and evaluation of thermosensitive chitosan/collagen/α, β-glycerophosphate hydrogels for tissue regeneration,” Carbohydr. Polym., vol. 167, pp. 145–157, 2017.
[9] ISO, “ISO 10993-5. Biological evaluation of medical devices — Part 5: Tests for in vitro cytotoxicity. International Standard.,” 2009.
[10] J. Berger, M. Reist, A. Chenite, O. Felt-Baeyens, J. M. Mayer, and R. Gurny, “Pseudo-thermosetting chitosan hydrogels for biomedical application,” Int. J. Pharm., vol. 288, no. 2, pp. 197–206, 2005.
[11] A. Chenite et al., “Novel injectable neutral solutions of chitosan form biodegradable gels in situ,” Biomaterials, vol. 21, no. 21, pp. 2155–2161, 2000.
[12] J. Cho, M. C. Heuzey, A. Bégin, and P. J. Carreau, “Physical gelation of chitosan in the presence of β-glycerophosphate: The effect of temperature,” Biomacromolecules, vol. 6, no. 6, pp. 3267–3275, 2005.
[13] R. Ahmadi and J. D. De Bruijn, “Biocompatibility and gelation of chitosan-glycerol phosphate hydrogels,” J. Biomed. Mater. Res. - Part A, vol. 86, no. 3, pp. 824–832, 2008.
[14] L. F. and H. J., “Effects of dexamethasone, ascorbic acid and β-glycerophosphate on the osteogenic differentiation of stem cells in vitro,” Stem Cell Res. Ther., vol. 4, no. 5, p. 1, 2013.
[15] R. A. H. Fernández, “Kinasas y fosfatasas: el yin y el yan de la vida,” Rev. Habanera Ciencias Medicas, vol. 11, no. 1, pp. 15–24, 2012.
[16] L. Sapio and S. Naviglio, “Inorganic phosphate in the development and treatment of cancer: A Janus Bifrons?,” World J. Clin. Oncol., vol. 6, no. 6, pp. 198–201, 2015.
[17] J. Y. Lai, “The role of bloom index of gelatin on the interaction with retinal pigment epithelial cells,” Int. J. Mol. Sci., vol. 10, no. 8, pp. 3442–3456, 2009.
[18] T. P. Kraehenbuehl et al., “Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: Systematic modulation of a synthetic cell-responsive PEG-hydrogel,” Biomaterials, vol. 29, no. 18, pp. 2757–2766, 2008.
[19] H. Wang et al., “Promotion of cardiac differentiation of brown adipose derived stem cells by chitosan hydrogel for repair after myocardial infarction,” Biomaterials, vol. 35, no. 13, pp. 3986–3998, 2014.
[20] M. Kapałczyńska et al., “2D and 3D cell cultures – a comparison of different,” Arch. Med. Sci., vol. 14, no. 4, pp. 910–919, 2016.
[21] C. M. Madl and S. C. Heilshorn, “Engineering Hydrogel Microenvironments to Recapitulate the Stem Cell Niche,” Annu. Rev. Biomed. Eng., vol. 20, pp. 21–47, 2018.