Encapsulation of protein microfiber networks supporting pancreatic islets†
Joseph A. M. Steele
Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada, K7L 3N6
Search for more papers by this authorAnnelise E. Barron
Department of Bioengineering, Stanford University, Stanford, California 94305-5444
Search for more papers by this authorEuridice Carmona
Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada, H1T 2M4
Department of Medicine, University of Montreal, Montreal, Quebec, Canada, H3T 1J4
Search for more papers by this authorJean-Pierre Hallé
Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada, H1T 2M4
Department of Medicine, University of Montreal, Montreal, Quebec, Canada, H3T 1J4
Search for more papers by this authorCorresponding Author
Ronald J. Neufeld
Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada, K7L 3N6
Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada, K7L 3N6Search for more papers by this authorJoseph A. M. Steele
Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada, K7L 3N6
Search for more papers by this authorAnnelise E. Barron
Department of Bioengineering, Stanford University, Stanford, California 94305-5444
Search for more papers by this authorEuridice Carmona
Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada, H1T 2M4
Department of Medicine, University of Montreal, Montreal, Quebec, Canada, H3T 1J4
Search for more papers by this authorJean-Pierre Hallé
Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada, H1T 2M4
Department of Medicine, University of Montreal, Montreal, Quebec, Canada, H3T 1J4
Search for more papers by this authorCorresponding Author
Ronald J. Neufeld
Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada, K7L 3N6
Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada, K7L 3N6Search for more papers by this authorHow to cite this article: Steele JAM, Barron AE, Carmona E, Hallé J-P, Neufeld RJ. 2012. Encapsulation of protein microfiber networks supporting pancreatic islets. J Biomed Mater Res Part A 2012:100A:3384–3391.
Abstract
Networks of discrete, genipin-crosslinked gelatin microfibers enveloping pancreatic islets were incorporated within barium alginate microcapsules. This novel technique enabled encapsulation of cellular aggregates in a spherical fibrous matrix <300 μm in diameter. Microfibers were produced by vortex-drawn extrusion within an alginate support matrix. Optimization culminated in a hydrated fiber diameter of 22.3 ± 0.4 μm, a significant reduction relative to that available through current gelatin microfiber spinning techniques, while making the process more reliable and less labor intensive. Microfibers were encapsulated at 40 vol % within 294 ± 4 μm 1.6% barium alginate microparticles by electrostatic-mediated dropwise extrusion. Pancreatic islets extracted from Sprague Dawley rats were encapsulated within the microparticles and analyzed over 21 days. Acridine orange and propidium iodide fluorescent viability staining and light microscopy indicated a significant increase in viability for islets within the fiber-embedded particles relative to fiber-free controls at days 7, 14, and 21. The fiber-embedded system also promoted cellular aggregate cohesion, reducing the incidence of dispersed islet morphologies within the capsules from 31 to 8% at day 21. Further enquiry into benefits of islet encapsulation within a protein fiber network will be the subject of future investigation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3384–3391, 2012.
REFERENCES
- 1 Atkinson MA. ADA Outstanding Scientific Achievement Lecture 2004. Thirty years of investigating the autoimmune basis for type 1 diabetes: Why can't we prevent or reverse this disease? Diabetes 2005; 54: 1253–1263.
- 2 Kobayashi N. Bioartificial pancreas for the treatment of diabetes. Cell Transplant 2008; 17: 11–17.
- 3 Hallé J, De Vos P. The need for new therapeutic approaches and the bioartificial endocrine pancreas. In: J Hallé, P De Vos, R L, editors. The Bioartificial Pancreas and Other Biohybrid Techniques. Kerala, India: Transworld Research Network; 2009. p 1–26.
- 4 Lim F, Sun AM. Microencapsulated islets as bioartificial endocrine pancreas. Science 1980; 210: 908–910.
- 5 Orive G, Hernandez RM, Rodriguez Gascon A, Calafiore R, Chang TM, de Vos P, Hortelano G, Hunkeler D, Lacik I, Pedraz JL. History, challenges and perspectives of cell microencapsulation. Trends Biotechnol 2004; 22: 87–92.
- 6 Zimmermann H, Zimmermann D, Reuss R, Feilen PJ, Manz B, Katsen A, Weber M, Ihmig FR, Ehrhart F, Gessner P, Behringer M, Steinbach A, Wegner LH, Sukhorukov VL, Vásquez JA, Schneider S, Weber MM, Volke F, Wolf R, Zimmermann U. Towards a medically approved technology for alginate-based microcapsules allowing long-term immunoisolated transplantation. J Mater Sci Mater Med 2005; 16: 491–501.
- 7 Langlois G, Dusseault J, Bilodeau S, Tam SK, Magassouba D, Halle JP. Direct effect of alginate purification on the survival of islets immobilized in alginate-based microcapsules. Acta Biomater 2009; 5: 3433–3440.
- 8 Augst AD, Kong HJ, Mooney DJ. Alginate hydrogels as biomaterials. Macromol Biosci 2006; 6: 623–633.
- 9 Robitaille R, Dusseault J, Henley N, Rosenberg L, Halle JP. Insulin-like growth factor II allows prolonged blood glucose normalization with a reduced islet cell mass transplantation. Endocrinology 2003; 144: 3037–3045.
- 10 Hamamoto Y, Fujimoto S, Inada A, Takehiro M, Nabe K, Shimono D, Kajikawa M, Fujita J, Yamada Y, Seino Y. Beneficial effect of pretreatment of islets with fibronectin on glucose tolerance after islet transplantation. Horm Metabol Res 2003; 35: 460–465.
- 11 Kaido T, Yebra M, Cirulli V, Montgomery AM. Regulation of human beta-cell adhesion, motility, and insulin secretion by collagen IV and its receptor alpha(1)beta(1). J Biol Chem 2004; 279: 53762–53769.
- 12 Salvay DM, Rives CB, Zhang XM, Chen F, Kaufman DB, Lowe WL, Shea LD. Extracellular matrix protein-coated scaffolds promote the reversal of diabetes after extrahepatic islet transplantation. Transplantation 2008; 85: 1456–1464.
- 13 Rowley JA, Madlambayan G, Mooney DJ. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 1999; 20: 45–53.
- 14 Lee BR, Hwang JW, Choi YY, Wong SF, Hwang YH, Lee DY, Lee SH. In situ formation and collagen-alginate composite encapsulation of pancreatic islet spheroids. Biomaterials 2012; 33: 837–845.
- 15 Chun S, Huang Y, Xie WJ, Hou Y, Huang RP, Song YM, Liu XM, Zheng W, Shi Y, Song CF. Adhesive growth of pancreatic islet cells on a polyglycolic acid fibrous scaffold. Transplant Proc 2008; 40: 1658–1663.
- 16 Daoud JT, Petropavlovskaia MS, Patapas JM, Degrandpre CE, DiRaddo RW, Rosenberg L, Tabrizian M. Long-term in vitro human pancreatic islet culture using three-dimensional microfabricated scaffolds. Biomaterials 2011; 32: 1536–1542.
- 17 Hou Y, Song C, Xie WJ, Wei Z, Huang RP, Liu W, Zhang ZL, Shi YB. Excellent effect of three-dimensional culture condition on pancreatic islets. Diabetes Res Clin Pract 2009; 86: 11–15.
- 18 Kawazoe N, Lin XT, Tateishi T, Chen GP. Three-dimensional cultures of rat pancreatic RIN-5F cells in porous PLGA-collagen hybrid scaffolds. J Bioact Compat Polym 2009; 24: 25–42.
- 19 Lucasclerc C, Massart C, Campion JP, Launois B, Nicol M. Long-term culture of human pancreatic-islets in an extracellular-matrix—Morphological and metabolic effects. Mol Cell Endocrinol 1993; 94: 9–20.
- 20 Landers R, Pfister A, Hubner U, John H, Schmelzeisen R, Mulhaupt R. Fabrication of soft tissue engineering scaffolds by means of rapid prototyping techniques. J Mater Sci 2002; 37: 3107–3116.
- 21 Ciardelli G, Gentile P, Chiono V, Mattioli-Belmonte M, Vozzi G, Barbani N, Giusti P. Enzymatically crosslinked porous composite matrices for bone tissue regeneration. J Biomed Mater Res A 2010; 92A: 137–151.
- 22 Del Guerra S, Bracci C, Nilsson K, Belcourt A, Kessler L, Lupi R, Marselli L, De Vos P, Marchetti P. Entrapment of dispersed pancreatic islet cells in CultiSpher-S macroporous gelatin microcarriers: Preparation, in vitro characterization, and microencapsulation. Biotechnol Bioeng 2001; 75: 741–744.
- 23 Yang CY, Chiu CT, Chang YP, Wang YJ. Fabrication of porous gelatin microfibers using an aqueous wet spinning process. Artif Cell Blood Substit Biotechnol 2009; 37: 173–176.
- 24 Sisson K, Zhang C, Farach-Carson MC, Chase DB, Rabolt JF. Evaluation of cross-linking methods for electrospun gelatin on cell growth and viability. Biomacromolecules 2009; 10: 1675–1680.
- 25 Torres-Giner S, Gimeno-Alcaniz JV, Ocio MJ, Lagaron JM. Comparative performance of electrospun collagen nanofibers cross-linked by means of different methods. ACS Appl Mater Interfaces 2009; 1: 218–223.
- 26
Matsuda S,
Iwata H,
Se N,
Ikada Y.
Bioadhesion of gelatin films crosslinked with glutaraldehyde.
J Biomed Mater Res
1999;
45:
20–27.
10.1002/(SICI)1097-4636(199904)45:1<20::AID-JBM3>3.0.CO;2-6 CAS PubMed Web of Science® Google Scholar
- 27
Sung HW,
Huang DM,
Chang WH,
Huang RN,
Hsu JC.
Evaluation of gelatin hydrogel crosslinked with various crosslinking agents as bioadhesives: In vitro study.
J Biomed Mater Res
1999;
46:
520–530.
10.1002/(SICI)1097-4636(19990915)46:4<520::AID-JBM10>3.0.CO;2-9 CAS PubMed Web of Science® Google Scholar
- 28 Liang HC, Chang WH, Lin KJ, Sung HW. Genipin-crosslinked gelatin microspheres as a drug carrier for intramuscular administration: In vitro and in vivo studies. J Biomed Mater Res A 2003; 65A: 271–282.
- 29
Sung HW,
Liang IL,
Chen CN,
Huang RN,
Liang HF.
Stability of a biological tissue fixed with a naturally occurring crosslinking agent (genipin).
J Biomed Mater Res
2001;
55:
538–546.
10.1002/1097-4636(20010615)55:4<538::AID-JBM1047>3.0.CO;2-2 CAS PubMed Web of Science® Google Scholar
- 30 Chang Y, Tsai CC, Liang HC, Sung HW. In vivo evaluation of cellular and acellular bovine pericardia fixed with a naturally occurring crosslinking agent (genipin). Biomaterials 2002; 23: 2447–2457.
- 31 Poncelet D, Desmet BP, Beaulieu C, Huguet ML, Fournier A, Neufeld RJ. Production of alginate beads by emulsification internal gelation. 2. Physicochemistry. Appl Microbiol Biotechnol 1995; 43: 644–650.
- 32 Poncelet D, Lencki R, Beaulieu C, Halle JP, Neufeld RJ, Fournier A. Production of alginate beads by emulsification internal gelation. 1. Methodology. Appl Microbiol Biotechnol 1992; 38: 39–45.
- 33 Hoesli CA, Raghuram K, Kiang RLJ, Mocinecova D, Hu XK, Johnson JD, Lacik I, Kieffer TJ, Piret JM. Pancreatic cell immobilization in alginate beads produced by emulsion and internal gelation. Biotechnol Bioeng 2011; 108: 424–434.
- 34 Gotoh M, Maki T, Kiyoizumi T, Satomi S, Monaco AP. An improved method for isolation of mouse pancreatic-islets. Transplantation 1985; 40: 437–438.
- 35 Yao CH, Liu BS, Chang CJ, Hsu SH, Chen YS. Preparation of networks of gelatin and genipin as degradable biomaterials. Mater Chem Phys 2004; 83: 204–208.
- 36 Fukae R, Midorikawa T. Preparation of gelatin fiber by gel spinning and its mechanical properties. J Appl Polym Sci 2008; 110: 4011–4015.
- 37
Robitaille R,
Pariseau JF,
Leblond FA,
Lamoureux M,
Lepage Y,
Halle JP.
Studies on small (<350 μm) alginate-poly-L-lysine microcapsules. III. Biocompatibility of smaller versus standard microcapsules.
J Biomed Mater Res
1999;
44:
116–120.
10.1002/(SICI)1097-4636(199901)44:1<116::AID-JBM13>3.0.CO;2-9 CAS PubMed Web of Science® Google Scholar
- 38 Bavamian S, Klee P, Britan A, Populaire C, Caille D, Cancela J, Charollais A, Meda P. Islet-cell-to-cell communication as basis for normal insulin secretion. Diabetes Obes Metabol 2007; 9: 118–132.