Abstract
The entrapment of enzymes, drugs, cells or tissue fragments in alginates cross-linked with Ca2+ or Ba2+ has great potential in basic research, biotechnology and medicine. The swelling properties and, in turn, the mechanical stability are key factors in designing an optimally cross-linked hydrogel matrix. These parameters depend critically on the cross-linking process and seemingly minor modifications in manufacture have a large impact. Thus, sensitive and non-invasive tools are required to determine the spatial homogeneity and efficacy of the cross-linking process. Here, we show for alginate microcapsules (between 400 µm and 600 µm in diameter) that advanced 1H NMR imaging, along with paramagnetic Cu2+ as contrast agent, can be used to validate the cross-linking process. Two- and three-dimensional images and maps of the spin-lattice relaxation time T 1 of Ba2+ cross-linked microcapsules exposed to external Cu2+ yielded qualitative as well as quantitative information about the accumulation of Cu2+ within and removal from microcapsules upon washing with Cu2+ free saline solution. The use of Cu2+ (having a slightly higher affinity constant to alginate than Ba2+) for gelling gave a complementary insight into the spatial homogeneity of the cross-linking process together with information about the mechanical stability of the microcapsules. The potential of this technique was demonstrated for alginates extracted from two different algal sources and cross-linked either externally by the conventional air-jet drop** method or internally by the "crystal gun" method.
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Acknowledgements
We are grateful to M. Behringer for his great help in the development of the "crystal gun" method. This work was supported by grants of the Bundesministerium für Bildung und Forschung (BMBF 0311588) to UZ, by BMBF grants (16SV1366/0 and 03N8707) to HZ and a research grant from IBMT to FV.
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Manz, B., Hillgärtner, M., Zimmermann, H. et al. Cross-linking properties of alginate gels determined by using advanced NMR imaging and Cu2+ as contrast agent. Eur Biophys J 33, 50–58 (2004). https://doi.org/10.1007/s00249-003-0341-8
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DOI: https://doi.org/10.1007/s00249-003-0341-8