[en] Transplantation of microencapsulated cells has been proposed as a cure for many types of endocrine disorders. Alginate-based microcapsules have been used in many of the feasibility studied addressing cure of the endocrine disorders, and different cancer types. Despite years of intensive research it is still not completely understood which factors have to be controlled and documented for achieving adequate mechanical stability. Here we studied the strength and elasticity of microcapsules of different composition with and without cell load. We compared strength (force) versus elasticity (time) required to compress individual microcapsule to 60% deformation. It is demonstrated that the alginate viscosity, the size of the beads, the alginate type, the gelling time, the storage solution and the cell load are dominant factors in determining the final strength of alginate-based microcapsules while the type of gelling ion, the polyamino acid incubation time, the type of polyamino acid and the culturing time determines the elasticity of the alginate-based microcapsules. Our data underpin the essence of documenting the above mentioned factors in studies on encapsulated cells as mechanical stability is an essential factor in the success and failure of encapsulated grafts.
Disciplines :
Oncology
Author, co-author :
Bhujbal, Swapnil V; Department of Pathology and Medical Biology, Immunoendocrinology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands, NorLux Neuro-Oncology Laboratory, Centre de Recherche Public de la Santé, 84, Val Fleuri, L-1586 Luxembourg, Luxembourg. Electronic address: s.bhujbal@umcg.nl.
Paredes-Juarez, Genaro A; Department of Pathology and Medical Biology, Immunoendocrinology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
NICLOU, Simone P. ; NorLux Neuro-Oncology Laboratory, Centre de Recherche Public de la Santé, 84, Val Fleuri, L-1586 Luxembourg, Luxembourg.
de Vos, Paul; Department of Pathology and Medical Biology, Immunoendocrinology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
External co-authors :
yes
Language :
English
Title :
Factors influencing the mechanical stability of alginate beads applicable for immunoisolation of mammalian cells.
Publication date :
September 2014
Journal title :
Journal of the Mechanical Behavior of Biomedical Materials
Andersen, T. et al., 2012. Alginates as biomaterials in tissue engineering. Carbohydrate Chemistry: Volume 37. The Royal Society of Chemistry, pp. 227-258. Available at:. http://dx.doi.org/10.1039/9781849732765-00227.
Bunger C.M., et al. Biocompatibility and surface structure of chemically modified immunoisolating alginate-PLL capsules. J. Biomed. Mater. Res. Part A 2003, 67(4):1219-1227.
Chan, E.-S. et al., 2011. Effect of formulation of alginate beads on their mechanical behavior and stiffness. Particuology, 9 (3), 228-234. Available at:. (accessed March 15, 2013). http://dx.doi.org/10.1016/j.partic.2010.12.002.
Chan, E.-S. et al., 2009. Prediction models for shape and size of ca-alginate macrobeads produced through extrusion-dripping method. J. Colloid Interface Sci., 338 (1), 63-72. Available at:. (accessed March 7, 2013). http://www.ncbi.nlm.nih.gov/pubmed/19604515.
Darrabie, M.D., Kendall, W.F., Opara, E.C., 2005. Characteristics of poly-l-ornithine-coated alginate microcapsules. Biomaterials, 26 (34), 6846-6852. Available at:. (accessed April 1, 2013). http://www.ncbi.nlm.nih.gov/pubmed/15955558.
Darrabie, M.D., Kendall, W.F., Opara, E.C., 2006. Effect of alginate composition and gelling cation on micro-bead swelling. J. Microencapsul., 23 (1), 29-37. Available at:. (accessed February 13, 2013). http://www.ncbi.nlm.nih.gov/pubmed/16830975.
Gautier, A. et al., 2011. Impact of alginate type and bead diameter on mass transfers and the metabolic activities of encapsulated C3A cells in bioartificial liver applications. Eur. Cells Mater., 21 (0), 94-106. Available at:. http://www.ncbi.nlm.nih.gov/pubmed/21267945.
Grant, G.T. et al., 1973. Biological interactions between polysaccharides and divalent cations: the egg-box model. FEBS Lett., 32 (1), 195-198. Available at:. http://www.sciencedirect.com/science/article/pii/0014579373807707.
Gugerli, R. et al., 2002. Quantitative study of the production and properties of alginate/poly-l-lysine microcapsules. J. Microencapsul., 19 (5), 571-590. Available at:. (accessed April 20, 2013). http://www.ncbi.nlm.nih.gov/pubmed/12433301.
Van Hoogmoed, C.G., Busscher, H.J., de Vos, P., 2003. Fourier transform infrared spectroscopy studies of alginate-PLL capsules with varying compositions. J. Biomed. Mater. Res. Part A, 67 (1), 172-178. Available at:. (accessed July 22, 2013). http://www.ncbi.nlm.nih.gov/pubmed/14517874.
Hunt, N.C. et al., 2010. Encapsulation of fibroblasts causes accelerated alginate hydrogel degradation. Acta Biomater., 6 (9), 3649-3656. Available at: (accessed January 29, 2013). http://www.ncbi.nlm.nih.gov/pubmed/20307693.
King, A., 2001. Evaluation of Alginate Microcapsules for Use in Transplantation of Islets of Langerhans. Uppsala University. Available at:. http://uu.diva-portal.org/smash/get/diva2:160942/FULLTEXT01.
Kizilel S., Garfinkel M., Opara E. The bioartificial pancreas: progress and challenges. Diabetes Technol. Ther. 2005, 7(6):968-985.
Klokk, T.I., Melvik, J.E., 2002. Controlling the size of alginate gel beads by use of a high electrostatic potential. J. Microencapsul., 19 (4), 415-424. Available at:. (accessed March 8, 2013). http://www.ncbi.nlm.nih.gov/pubmed/12396380.
Kulseng, B. et al., 1997. Alginate polylysine microcapsules as immune barrier: permeability of cytokines and immunoglobulins over the capsule membrane. Cell Transplant. 6 (4), pp. 387-394. Available at:. (Accessed January 31, 2013). http://www.ncbi.nlm.nih.gov/pubmed/9258512.
Lee, C.S.D. et al., 2010. Regulating in vivo calcification of alginate microbeads. Biomaterials, 31 (18), 4926-4934. Available at: (accessed April 22, 2013). http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3358131&tool=pmcentrez&rendertype=abstract.
Leung A., et al. Synthesis and characterization of alginate/poly-l-ornithine/alginate microcapsules for local immunosuppression. J. Microencapsul. 2008, 25(6):387-398.
Lewińska, D., Rosiński, S., Weryński, A., 2004. Influence of process conditions during impulsed electrostatic droplet formation on size distribution of hydrogel beads. Artif. Cells, Blood Substitues, Immobilization Biotechnol., 32 (1), 41-53. Available at:. (accessed May 6, 2013). http://www.ncbi.nlm.nih.gov/pubmed/15027800.
Ludwig, B. et al., 2012. Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist. Proc. Nat. Acad. Sci. U.S.A., 109 (13), 5022-5027. Available at:. (accessed April 28, 2014). http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3324017&tool=pmcentrez&rendertype=abstract.
Mørch Y.A., et al. Effect of Ca2+, Ba2+, and Sr2+ on alginate microbeads. Biomacromolecules 2006, 7(5):1471-1480.
Mørch, Ý.A., 2008. Novel Alginate Microcapsules for Cell Therapy-A Study of the Structure-Function Relationships in Native and Structurally Engineered Alginates. Norwegian University of Science and Technology. Available at:. http://ntnu.diva-portal.org/smash/record.jsf?pid=diva2:123854.
Orive, G. et al., 2006. Biocompatibility of alginateâ€"poly-l-lysine microcapsules for cell therapy. Biomaterials, 27 (20), 3691. Available at:. http://www.sciencedirect.com/science/article/pii/S014296120600192X.
Orive G., et al. Cell encapsulation: promise and progress. Nat. Med. 2003, 9(1):104-107.
Ponce, S. et al., 2006. Chemistry and the biological response against immunoisolating alginate-polycation capsules of different composition. Biomaterials, 27 (28), 4831-4839. Available at: (accessed February 5, 2013). http://www.ncbi.nlm.nih.gov/pubmed/16766026.
Rokstad, A.M. et al., 2002. Microencapsulation of cells producing therapeutic proteins: optimizing cell growth and secretion. Cell Transplant., 11 (4), 313-324. Available at: (accessed February 8, 2013). http://www.ncbi.nlm.nih.gov/pubmed/12162372.
Shen, F. et al., 2009. Mechanically enhanced microcapsules for cellular gene therapy. J. Biomed. Mater. Res. Part B Appl. Biomater., 90 (1), 350-361. Available at: (accessed May 8, 2013). http://www.ncbi.nlm.nih.gov/pubmed/19090494.
Shoichet M.S., et al. Stability of hydrogels used in cell encapsulation: an in vitro comparison of alginate and agarose. Biotechnol. Bioeng. 1996, 50(4):374-381.
Simpson, N.E. et al., 2004. The role of the CaCl2-guluronic acid interaction on alginate encapsulated betaTC3 cells. Biomaterials, 25 (13), 2603-2610. Available at: (accessed May 6, 2013). http://www.ncbi.nlm.nih.gov/pubmed/14751746.
Smidsrod, O., 1974. Molecular basis for some physical properties of alginates in the gel state. Faraday Discuss. Chem. Soc., 57 (0), 263-274. Available at:. http://dx.doi.org/10.1039/DC9745700263.
Smidsrød, O., Glover, R.M., Whittington, S.G., 1973. The relative extension of alginates having different chemical composition. Carbohydr. Res., 27 (1), 107-118. Available at: (accessed April 9, 2013). http://dx.doi.org/10.1016/S0008-6215(00)82430-1.
Stabler, C. et al., 2001. The effects of alginate composition on encapsulated betaTC3 cells. Biomaterials, 22 (11), 1301-1310. Available at: (accessed February 8, 2013). http://www.ncbi.nlm.nih.gov/pubmed/11336302.
Stokke, B.T. et al., 1991. Distribution of uronate residues in alginate chains in relation to alginate gelling properties. Macromolecules, 24 (16), 4637-4645. Available at:. http://pubs.acs.org/doi/abs/10.1021/ma00016a026.
Stokke, B.T. et al., 1993a. Distribution of uronate residues in alginate chains in relation to alginate gelling properties-2: Enrichment of β-d-mannuronic acid and depletion of α-l-guluronic acid in sol fraction. Carbohydr. Polym., 21 (1), 39-46. Available at:. (accessed March 13, 2014). http://www.sciencedirect.com/science/article/pii/014486179390115K.
Stokke, B.T., Smidsrod, O., Brant, D.A., 1993b. Predicted influence of monomer sequence distribution and acetylation on the extension of naturally occurring alginates, Carbohydrate Polymers. 22, 57-66.
Strand, B.L. et al., 2002. Alginate-polylysine-alginate microcapsules: effect of size reduction on capsule properties. J. Microencapsul., 19 (5), 615-630. Available at: (accessed February 13, 2013). http://www.ncbi.nlm.nih.gov/pubmed/12433304.
Strand, B.L. et al., 2003. Visualization of alginate-poly-l-lysine-alginate microcapsules by confocal laser scanning microscopy. Biotechnol. Bioeng., 82 (4), 386-394. Available at:. (accessed March 3, 2013). http://www.ncbi.nlm.nih.gov/pubmed/12632394.
Tam, S.K. et al., 2011. Biocompatibility and physicochemical characteristics of alginate-polycation microcapsules. Acta Biomater., 7 (4), 1683-1692. Available at:. (accessed March 10, 2014). http://www.ncbi.nlm.nih.gov/pubmed/21145438.
Thanos, C.G., Bintz, B.E., Emerich, D.F., 2007. Stability of alginate-polyornithine microcapsules is profoundly dependent on the site of transplantation. J. Biomed. Mater. Res. Part A, 81 (1), 1-11. Available at:. (accessed January 30, 2013). http://www.ncbi.nlm.nih.gov/pubmed/17089418.
Thu B., Bruheim P., Espevik T., Smidsrod O., et al. Alginate polycation microcapsules. I. Interaction between alginate and polycation. Biomaterials 1996, 17(10):1031-1040.
Thu, B., Bruheim, P., Espevik, T., Smidsrød, O., et al., 1996b. Alginate polycation microcapsules. II. Some functional properties. Biomaterials, 17 (11), 1069-1079. Available at: (accessed February 13, 2013). http://www.ncbi.nlm.nih.gov/pubmed/8718966.
Vaithilingam, V. et al., 2011. Effect of prolonged gelling time on the intrinsic properties of barium alginate microcapsules and its biocompatibility. J. Microencapsul., 28 (6), 499-507. Available at:. (accessed February 19, 2013). http://www.ncbi.nlm.nih.gov/pubmed/21827357.
De Vos P., De Haan B., Pater J., et al. Association between capsule diameter, adequacy of encapsulation, and survival of microencapsulated rat islet allografts. Transplantation 1996, 62(7):893-899.
De Vos, P., De Haan, B., Wolters, G.H., et al., 1996b. Factors influencing the adequacy of microencapsulation of rat pancreatic islets. Transplantation, 62 (7), 888-893. Available at:. (accessed April 9, 2013). http://www.ncbi.nlm.nih.gov/pubmed/8878379.
De Vos P., et al. Improved biocompatibility but limited graft survival after purification of alginate for microencapsulation of pancreatic islets. Diabetologia 1997, 40(3):262-270.
De Vos, P. et al., 2009. Multiscale requirements for bioencapsulation in medicine and biotechnology. Biomaterials, 30 (13), 2559-2570. Available at:. (accessed May 6, 2013). http://www.ncbi.nlm.nih.gov/pubmed/19201460.
De Vos, P. et al., 2012. The association between in vivo physicochemical changes and inflammatory responses against alginate based microcapsules. Biomaterials, 33 (22), 5552-5559. Available at: (accessed May 31, 2013). http://www.ncbi.nlm.nih.gov/pubmed/22560199.
De Vos, P. et al., 2007. Zeta-potentials of alginate-PLL capsules: a predictive measure for biocompatibility? J. Biomed. Mater. Res. Part A, 80 (4), 813-819. Available at:. (accessed February 13, 2013). http://www.ncbi.nlm.nih.gov/pubmed/17058213.
De Vos, P., Haan. B. D., Van Schilfgaarde, R., 1997. Effect of the alginate the biocompatibility polylysine microcapsule. Biomaterials 18, 273-278.
De Vos, P., Hoogmoed, C.G., Busscher, H.J., 2002. Chemistry and biocompatibility of alginate-PLL capsules for immunoprotection of mammalian cells. J. Biomed. Mater. Res., 60 (2), 252-259. Available at:. (accessed May 8, 2013). http://www.ncbi.nlm.nih.gov/pubmed/11857431.
Zhang, J., Daubert, C.R., Allen Foegeding, E., 2007. A proposed strain-hardening mechanism for alginate gels. J. Food Eng., 80 (1), 157-165. Available at:. (accessed February 28, 2013). http://linkinghub.elsevier.com/retrieve/pii/S026087740600402X.
Zhang, Z., Saunders, R., Thomas, C.R., 1999. Mechanical strength of single microcapsules determined by a novel micromanipulation technique. J. Microencapsul., 16 (1), 117-124. Available at:. (accessed June 20, 2013). http://www.ncbi.nlm.nih.gov/pubmed/9972508.
Zhao, L., Zhang, Z., 2004. Mechanical characterization of biocompatible microspheres and microcapsules by direct compression. Artif. Cells, Blood Substitues, Immobilization Biotechnol., 32 (1), 25-40. Available at:. (accessed June 20, 2013). http://www.ncbi.nlm.nih.gov/pubmed/15027799.