Investigation and Characterization of Agarose-Gelatin Blend Hydrogel, as a Cellular Carrier Substrate for Cell Therapy Application

Imani, Rana; Rahnama Moshtaq, Parisa; Hojati Emami, Shahriar; Jalili, Sasan; Sharifi, Ali Mohammad

doi:10.22041/ijbme.2010.13349

Investigation and Characterization of Agarose-Gelatin Blend Hydrogel, as a Cellular Carrier Substrate for Cell Therapy Application

Document Type : Full Research Paper

Authors

Rana Imani ¹

Parisa Rahnama Moshtaq ²

Shahriar Hojati Emami ³

Sasan Jalili ²

Ali Mohammad Sharifi ⁴

¹ PhD Student, Biomaterial Group, Laboratory of Tissue Engineering, School of BioMedical Engineering, Amir Kabir University of Technology

² M.Sc Student, Biomaterial Group, Laboratory of Tissue Engineering, School of BioMedical Engineering, Amir Kabir University of Technology

³ Assistant Professor, Biomaterial Group, School of BioMedical Engineering, Amir Kabir University of Technology

⁴ Professor, Razi Institute for Drug Research and Department of Pharmacology, Tehran University of Medical Sciences

https://doi.org/10.22041/ijbme.2010.13349

Abstract

Cell therapy based on cell encapsulation technology holds out the promise of the treatment of many diseases. The technology of cell encapsulation represents a strategy in which cells that secrete therapeutic products are immobilized and immunoprotected within polymeric and biocompatible carriers. Hydrogels - highly hydrated polymer networks- have ideal characteristics for this application because of good biocompatibility and mimicking natural ECM properties. They can homogeneously incorporate and suspend cells, growth factors, and other bioactive compounds. Temperature-sensitive hydrogels, which can form implants in situ in response to temperature change, from ambient to body temperature, have been extensively used in various cell encapsulation, and tissue repair. The objective of this study was preparation, Characterization and selection the optimum composition of agarose-gelatin blend hydrogel, for cell encapsulation application. In order to obtain hydrogel with appropriate properties, rheological, mechanical, and structural characteristics of obtained hydrogels were examined. Furthermore, the stability of samples was characterized by degradation and gelatin release measurements under physiological condition. Cell attachment and cytotoxicity analysis were also performed. Based on the results, hydrogel containing a 1:1 mixture of gelatin and agarose exhibited sol-to-gel transition near body temperature. Samples contain 50% agarose and more, exhibited mechanical integrity under physiological condition. Indentation test of the mechanical properties demonstrated viscoelastic behavior of the blend gelatin-agarose hydrogels under static load; however by increasing the agarose portion, hydrogel behaved more elastically. In vitro biocompatibility experiments showed undetectable cytotoxicity of the hydrogels. Also adding gelatin to agarose modified cell attachment behavior. The results of this study indicate the possibility of the potential use of prepared thermo-responsive agarose/gelatin conjugate with nearly same portion of two components as cell encapsulation carrier.

Keywords

Cell therapy

Encapsulasion

Temperature-sensitive hydrogel

Agarose

Gelatin

Subjects

[1] Ainhoa M., Aitziber P., Gorka O., Rosa M H., de María C., Luis P. J., Review: Cell micro encapsulation technology: Towards clinical application, Journal of Controlled Release, 2008; 132:. 76–83.

[2] Babensee J., Anderson J. M., McIntire L., Mikos A.G., Host response to tissue engineered devices, Advanced Drug Delivery Reviews, 1998; 33: 111–139.

[3] Wilson J., Chaikof E., Challenges and emerging technologies in the immunoisolation of cells and tissues, Advanced Drug Delivery Reviews, 2008; 60: 124–145.

[4] Zimmermann H., Ehrhart F., Zimmermann D., Müller K., Katsen-Globa A., Behringer M., Feilen P. J., Gessner P., Zimmermann G., Shirley S. G., Weber M.M., Metze J., Zimmermann U., Hydrogel – based encapsulation of biological, functional tissue: fundamentals, technologies and applications, Apply Physics, 2007; 89: 909–922.

[5] Baroli B., Hydrogels for Tissue Engineering and Delivery of Tissue-Inducing Substances, Journal of Pharmacutical Sciences, 2007; 96: 2197-2223.

[6] Liu J., Lin Sh., Li L., Liu E., Release of theophylline from polymer blend hydrogels, International Journal of Pharmaceutics, 2005; 298: 117–125.

[7] Li R.H., Altreuter D.H., Gentile F.T., Transport Characterization of Hydrogel Matrices for Cell Encapsulation, Biotechnology and Bioengineering, 1996; 50: 365-373.

[8] Martínez-Díaz G.J., Nelson D., Crone W.C., Kao W.J., Mechanical and Chemical Analysis of Gelatin-Based Hydrogel Degradation, Macromolecular Chemistry and Physics, 2003; 204: 1898 –1908.

[9] Sakai Sh., Hashimoto I., Kawakami K., Agarose – gelatin conjugate for adherent cell-enclosing capsules, Biotechnology Letters, 2007; 29: 731–735.

[10] Verma V., Verma P., Kar S. K., Ray P. and Ray A R., Fabrication of Agar-Gelatin Hybrid Scaffolds Using a Novel Entrapment Method for In Vitro Tissue Engineering Applications, Biotechnology and Bioengineering, 2007; 96: 392-400.

[11] Emami Sh., Crosslinked poly(ethylene oxide) hydrogels, Journal of Applied Polymer Science, 2003; 88; 1451 – 55.

[12] Lu H. F., Targonsky E. D., Wheeler M., B. Cheng Y. L., Thermally Induced Gelable Polymer Networks for Living Cell Encapsulation, Biotechnology and Bioengineering, 2007; 96: 146-155.

[13] Anseth K.S., Bowman C.N. and BrannonPeppas L., Review: Mechanical properties of hydrogels and their experimental determination, Biomaterials, 1996; 17: 1647-57.