Abstract
The role of phosphate buffer saline solution (PBS) was investigated here as a solvent in the polycondensation synthesis of an injectable agar-carbomer based hydrogel, a promising new material specifically intended for regenerative medicine applications. The effects of PBS, with respect to standard distilled water (DW), were quantitatively assessed. Experiments were performed both from physico-chemical and biological points of view. Titration showed higher stability due to the presence of the buffer solution; ESEM analysis confirmed its distribution along the polymeric fibers and infrared spectroscopy showed the consequent anionic nature of the polymeric network. This electrostatic nature of the matrix was confirmed by mass equilibrium swelling data performed at different pH values of the swelling medium. A very relevant role of the solvent was observed also with respect to cell housing inside such hydrogels: living cell counts showed a high amount of cells surviving the latency period of encapsulation in hydrogel when PBS was applied while only very few survived in a deionized water based gel. Obtained data allowed a novel understanding of the causeeffect cascades of all observed phenomena which suggest the PBS fundamental role both in fine control of hydrogel preparation and in material tuning according to the specific needs of different target tissues; the latter being a feature of primary importance when applying hydrogels as cell carriers in regenerative medicine applications.
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Brännvall, K., Bergman, K., Wallenquist, U., Svahn, S., Bowden, T., Hilborn, J., & Forsberg-Nilsson, K. (2007). Enhanced neuronal differentiation in a three-dimensional collagenhyaluronan matrix. Journal of Neuroscience Research, 85, 2138–2146. DOI: 10.1002/jnr.21358.
Chan, A.W., Whitney, R. A., & Neufeld, R. J. (2009). Semisynthesis of a controlled stimuli-responsive alginate hydrogel. Biomacromolecules, 10, 609–616. DOI: 10.1021/bm800594f.
Choi, J., Bodugoz-Senturk, H., Kung, H. J., Malhi, A. S., & Muratoglu, O. K. (2007). Effects of solvent dehydration on creep resistance of poly(vinyl alcohol) hydrogel. Biomaterials, 28, 772–780. DOI: 10.1016/j.biomaterials.2006.09.049.
Crompton, K. E., Goud, J. D., Bellamkonda, R. V., Gengenbach, T. R., Finkelstein, D. I., Horne, M. K., & Forsythe, J. S. (2007). Polylysine-functionalised thermoresponsive chitosan hydrogel for neural tissue engineering. Biomaterials, 28, 441–449. DOI: 10.1016/j.biomaterials.2006.08.044.
Dulbecco, R., & Vogt, M. (1954). Plaque formation and isolation of pure lines with poliomyelitis viruses. The Journal of Experimental Medicine, 99, 167–182. DOI: 10.1084/jem.99.2.167.
Dumitriu, S. (2002). Polymeric biomaterials (2nd ed.). New York, NY, USA: Marcel Dekker.
Ebara, M., Yamato, M., Nagai, S., Aoyagi, T., Kikuchi, A., Sakai, K., & Okano, T. (2004). Incorporation of new carboxylate functionalized co-monomers to temperature-responsive polymer-grafted cell culture surfaces. Surface Science, 570, 134–141. DOI: 10.1016/j.susc.2004.06.183.
Fatimi, A., Tassin, J.-F., Turczyn, R., Axelos, A. V. M., & Weiss, P. (2009). Gelation studies of a cellulose-based biohydrogel: The influence of pH, temperature and sterilization. Acta Biomaterialia, 5, 3423–3432. DOI: 10.1016/j.actbio. 2009.05.030.
Flory, P. J. (1953). Principles of polymer chemistry. Ithaca, NY, USA: Cornell University Press.
Gorbet, M. B., Tanti, N. C., Jones, L., & Sheardown, H. (2010). Corneal epithelial cell biocompatibility to silicone hydrogel and conventional hydrogel contact lens packaging solutions. Molecular Vision, 16, 272–282.
Garripelli, V. K., Kim, J.-K., Namgung, R., Kim, W. J., Repka, M. A., & Jo, S. (2010). A novel thermosensitive polymer with pH-dependent degradation for drug delivery. Acta Biomaterialia, 6, 477–485. DOI: 10.1016/j.actbio.2009.07.005.
Hynd, M. R., Turner, J. N., & Shain, W. (2007). Applications of hydrogels for neural cell engineering. Journal of Biomaterial Science, Polymer Edition, 18, 1223–1244. DOI: 10.1163/156856207782177909.
Khan, F., Tare, R. S., Oreffo, R. O. C., & Bradley, M. (2009). Versatile biocompatible polymer hydrogels: scaffolds for cell growth. Angewandte Chemie International Edition, 48, 978–982. DOI: 10.1002/anie.200804096.
Kuckling, D. (2009) Responsive hydrogel layers—from synthesis to applications. Colloid and Polymer Science, 287, 881–891. DOI: 10.1007/s00396-009-2060-x.
Lanza, R., Langer, R., & Vacanti, J. (2000). Principles of tissue engineering. San Diego, CA, USA: Academic Press.
Little, L., Healy, K. H., & Schaffer, D. (2008). Engineering biomaterials for synthetic neural stem cell microenvironments. Chemical Reviews, 108, 1787–1796. DOI: 10.1021/cr078228t.
Luo, R., & Li, H. (2009). A modeling study of the effect of environmental ionic valence on the mechanical characteristics of pH-electrosensitive hydrogel. Acta Biomaterialia, 5, 2920–2928. DOI: 10.1016/j.actbio.2009.04.009.
Luo, Y., & Shoichet, M. S. (2004). A photolabile hydrogel for guided three-dimensional cell growth and migration. Nature Materials, 3, 249–253. DOI: 10.1038/nmat1092.
Perale, G., Giordano, C., Bianco, F., Daniele, F., Rossi, F., Matteoli, M., & Masi, M. (2008). Hydrogel for cell housing in the brain and in the spinal cord. The International Journal of Artificial Organs, 31, 613.
Rajagopal, K., Lamm, M. S., Haines-Butterick, L. A., Pochan, D. J., & Schneider, J. P. (2009). Tuning the pH responsiveness of β-hairpin peptide folding, self-assembly, and hydrogel material formation. Biomacromolecules, 10, 2619–2625. DOI: 10.1021/bm900544e.
Sambrook, J., Fritsch, E. F., & Maniatis, T. (1989). Molecular cloning: A laboratory manual (2nd ed). New York, NY, USA: Cold Spring Harbor Laboratory Press.
Shim, W. S., Yoo, J. S., Bae, Y. H., & Lee, D. S. (2005). Novel injectable pH and temperature sensitive block copolymer hydrogel. Biomacromolecules, 6, 2930–2934. DOI: 10.1021/bm050521k.
Shoichet, M. S. (2010). Polymer scaffolds for biomaterials applications. Macromolecules, 43, 581–591. DOI: 10.1021/ma901530r.
Simonetta, M., & Carrà, S. (1969). General and theoretical aspects of the COOH and COOR groups. In S. Patai (Ed.), Carboxylic acids and esters. New York, NY, USA: Wiley. DOI: 10.1002/9780470771099.ch1.
Slaughter, B. V., Khurshid, S. S., Fisher, O. Z., Khademhosseini, A., & Peppas, N. A. (2009). Hydrogels in regenerative medicine. Advanced Materials, 21, 3307–3329. DOI: 10.1002/adma.200802106.
Tabata, Y. (2009). Biomaterial technology for tissue engineering applications. Journal of the Royal Society Interface, 6, S311–S324. DOI: 10.1098/rsif.2008.0448.focus.
Tunesi, M., Rossi, F., Daniele, F., Bossio, C., Perale, G., Bianco, F., Matteoli, M., Giordano, C., & Cigada, A. (2009). A novel hydrogel formulation as promising cell carrier. Regenerative Medicine, 4, S271–S306. DOI: 10.2217/rme.09.s8.
Vidović, E., Klee, D., & Höcker, H. (2009). Degradation behavior of hydrogels from poly(vinyl alcohol)-graft-[poly(rac-lactide)/poly(rac-lactide-co-glycolide)]: Influence of the structure and composition on the material’s stability. Journal of Applied Polymer Science, 112, 1538–1545. DOI: 10.1002/app.29445.
Wang, C., Adrianus, G. N., Sheng, N., Toh, S., Gong, Y., & Wang, D.-A. (2009). In vitro performance of an injectable hydrogel/microsphere based immunocyte delivery system for localised anti-tumour activity. Biomaterials, 30, 6986–6995. DOI: 10.1016/j.biomaterials.2009.09.006.
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Rossi, F., Perale, G. & Masi, M. Biological buffered saline solution as solvent in agar-carbomer hydrogel synthesis. Chem. Pap. 64, 573–578 (2010). https://doi.org/10.2478/s11696-010-0052-4
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DOI: https://doi.org/10.2478/s11696-010-0052-4