Abstract
Type 1 diabetes (T1D) is an autoimmune disease where pancreatic beta cells, the only insulin-producing cells, are attacked and destroyed by a patient’s own immune system. Currently, insulin injection or infusion remains the only standard treatment for T1D. However, insulin does not cure this disease nor does it permit minute-to-minute regulation as pancreatic beta cells do. This can lead to various hyper/hypoglycemia-associated complications. Islet transplantation provides a potential alternative therapy and has been successfully used to treat patients. However, the severe shortage of donor organs and the life-long immunosuppression that are required by such a transplant have prevented this approach from being widely used. Recently, transplantation of encapsulated or immunoprotected islets or stem cell-derived beta-like cells has become an increasingly promising approach. In order to accomplish the encapsulation and immunoprotection, a variety of materials and microscale techniques have been developed. This chapter provides a brief overview of the different methods developed to fabricate microscale encapsulation materials and devices. We conclude that although challenging, fabrication and material innovation may one day make the cell encapsulation a clinical reality for T1D patients.
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Abbreviations
- T1D:
-
Type 1 diabetes
- STZ:
-
Streptozotocin
- PVA:
-
Polyvinyl alcohol
- ECM:
-
Extracellular matrix
- PEG:
-
Polyethylene glycol
- PLGA:
-
Poly(lactic-co-glycolic acid)
- NEEDs:
-
Nanofiber-enabled encapsulation devices
- HA:
-
Hyaluronic acid
- PDMS:
-
Polydimethylsiloxane
References
Todd JA (2010) Etiology of type 1 diabetes. Immunity 32:457–467
Bluestone JA, Herold K, Eisenbarth G (2010) Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 464:1293–1300
Gan MJ, Albanese-O’neill A, Haller MJ (2012) Type 1 diabetes: current concepts in epidemiology, pathophysiology, clinical care, and research. Curr Probl Pediatr Adolesc Health Care 42:269–291
Daneman D (2006) Type 1 diabetes. Lancet 367:847–858
Banting FG, Best CH (2007) The internal secretion of the pancreas. 1922. Indian J Med Res 125:251
Amer LD, Mahoney MJ, Bryant SJ (2014) Tissue engineering approaches to cell-based type 1 diabetes therapy. Tissue Eng Part B Rev 20(5):455–67
Atkinson MA, Eisenbarth GS, Michels AW (2014) Type 1 diabetes. Lancet 383:69–82
Hirsch IB (2009) Realistic expectations and practical use of continuous glucose monitoring for the endocrinologist. J Clin Endocrinol Metab 94:2232–2238
Donaghue KC, Chiarelli F, Trotta D, Allgrove J, Dahl‐Jorgensen K (2007) Microvascular and macrovascular complications. Pediatr Diabetes 8:163–170
Association, A. D. (2008) Diagnosis and classification of diabetes mellitus. Diabetes Care 31:S55–S60
Robertson RP (2004) Islet transplantation as a treatment for diabetes—a work in progress. N Engl J Med 350:694–705
White SA, Shaw JA, Sutherland DE (2009) Pancreas transplantation. Lancet 373:1808–1817
Stegall MD, Dean PG, Sung R, Guidinger MK, Mcbride MA, Sommers C, Basadonna G, Stock PG, Leichtman AB (2007) The rationale for the new deceased donor pancreas allocation schema. Transplantation 83:1156–1161
Lacy PE, Kostianovsky M (1967) Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16:35–39
Lim F, Sun AM (1980) Microencapsulated islets as bioartificial endocrine pancreas. Science 210:908–910
Orive G, Hernández RM, Rodríguez Gascón N, Calafiore R, Swi Chang TM, de Vos P, Hortelano G, Hunkeler D, Lacík I, Pedraz JL (2004) History, challenges and perspectives of cell microencapsulation. Trends Biotechnol 22:87–92
Zimmermann H, Zimmermann D, Reuss R, Feilen P, Manz B, Katsen A, Weber M, Ihmig F, Ehrhart F, Gessner P (2005) Towards a medically approved technology for alginate-based microcapsules allowing long-term immunoisolated transplantation. J Mater Sci Mater Med 16:491–501
Hernández RM, Orive G, Murua A, Pedraz JL (2010) Microcapsules and microcarriers for in situ cell delivery. Adv Drug Deliv Rev 62:711–730
Orive G, Hernández RM, Gascón AR, Calafiore R, Chang TM, De Vos P, Hortelano G, Hunkeler D, Lacík I, Shapiro AM, Pedraz JL (2003) Cell encapsulation: promise and progress. Nat Med 9:104–107
Elliott RB, Escobar L, Tan PL, Muzina M, Zwain S, Buchanan C (2007) Live encapsulated porcine islets from a type 1 diabetic patient 9.5 yr after xenotransplantation. Xenotransplantation 14:157–161
Kang A, Park J, Ju J, Jeong GS, Lee S-H (2014) Cell encapsulation via microtechnologies. Biomaterials 35:2651–2663
De Vos P, Marchetti P (2002) Encapsulation of pancreatic islets for transplantation in diabetes: the untouchable islets. Trends Mol Med 8:363–366
De Vos P, Lazarjani HA, Poncelet D, Faas MM (2014) Polymers in cell encapsulation from an enveloped cell perspective. Adv Drug Deliv Rev 67:15–34
Kendall WF Jr, Opara EC (2002) Immunoisolation techniques for islet cell transplantation. Expert Opin Biol Ther 2:503–511
Lanza RP, Butler DH, Borland KM, Staruk JE, Faustman DL, Solomon BA, Muller TE, Rupp RG, Maki T, Monaco AP (1991) Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression. Proc Natl Acad Sci 88:11100–11104
Tatarkiewicz K, Hollister-Lock J, Quickel RR, Colton CK, Bonner-Weir S, Weir GC (1999) Reversal of hyperglycemia in mice after subcutaneous transplantation of macroencapsulated islets. Transplantation 67:665–671
Qi M, Gu Y, Sakata N, Kim D, Shirouzu Y, Yamamoto C, Hiura A, Sumi S, Inoue K (2004) PVA hydrogel sheet macroencapsulation for the bioartificial pancreas. Biomaterials 25:5885–5892
Qi Z, Shen Y, Yanai G, Yang K, Shirouzu Y, Hiura A, Sumi S (2010) The in vivo performance of polyvinyl alcohol macro-encapsulated islets. Biomaterials 31:4026–4031
Aebischer P, Pochon N, Heyd B, Deglon N, Joseph J, Zurn A, Baetge E, Hammang J, Goddard M, Lysaght M (1996) Gene therapy for amyotrophic lateral sclerosis (Als) using a polymer encapsulated xenogenic cell line engineered to secrete hCNTF. Hum Gene Ther 7:851–860
Haisch A, Gröger A, Radke C, Ebmeyer J, Sudhoff H, Grasnick G, Jahnke V, Burmester G, Sittinger M (2000) Macroencapsulation of human cartilage implants: pilot study with polyelectrolyte complex membrane encapsulation. Biomaterials 21:1561–1566
Risbud MV, Bhargava S, Bhonde RR (2003) In vivo biocompatibility evaluation of cellulose macrocapsules for islet immunoisolation: implications of low molecular weight cut‐off. J Biomed Mater Res A 66:86–92
Prochorov A, Tretjak S, Goranov V, Glinnik A, Goltsev M (2008) Treatment of insulin dependent diabetes mellitus with intravascular transplantation of pancreatic islet cells without immunosuppressive therapy. Adv Med Sci 53:240–244
De Vos P, De Haan B, Wolters G, Strubbe J, Van Schilfgaarde R (1997) Improved biocompatibility but limited graft survival after purification of alginate for microencapsulation of pancreatic islets. Diabetologia 40:262–270
De Vos P, Vegter D, De Haan BJ, Strubbe JH, Bruggink JE, Van Schilfgaarde R (1996) Kinetics of intraperitoneally infused insulin in rats: functional implications for the bioartificial pancreas. Diabetes 45:1102–1107
Uludag H, De Vos P, Tresco PA (2000) Technology of mammalian cell encapsulation. Adv Drug Deliv Rev 42:29–64
Vos PD, Andersson A, Tam S, Faas M, Halle J (2006) Advances and barriers in mammalian cell encapsulation for treatment of diabetes. Immunol Endocr Metab Agents Med Chem 6:139–153
Lee M-K, Bae YH (2000) Cell transplantation for endocrine disorders. Adv Drug Deliv Rev 42:103–120
Machluf M, Orsola A, Boorjian S, Kershen R, Atala A (2003) Microencapsulation of Leydig cells: a system for testosterone supplementation. Endocrinology 144:4975–4979
Kim C, Lee KS, Kim YE, Lee K-J, Lee SH, Kim TS, Kang JY (2009) Rapid exchange of oil-phase in microencapsulation chip to enhance cell viability. Lab Chip 9:1294–1297
Du Y, Lo E, Ali S, Khademhosseini A (2008) Directed assembly of cell-laden microgels for fabrication of 3D tissue constructs. Proc Natl Acad Sci 105:9522–9527
Sugiura S, Oda T, Aoyagi Y, Satake M, Ohkohchi N, Nakajima M (2008) Tubular gel fabrication and cell encapsulation in laminar flow stream formed by microfabricated nozzle array. Lab Chip 8:1255–1257
Song W, An D, Kao D, Lu Y-C, Dai G, Chen S, Ma M (2014) Nanofibrous microposts and microwells of controlled shapes and their hybridization with hydrogels for cell encapsulation. ACS Appl Mater Interfaces
Ennis W, James DT (1950) A simple apparatus for producing droplets of uniform size from small volumes of liquids. Science 112:434–436
Sparks RE, Salemme RM, Meier PM, Litt MH, Lindan O (1969) Removal of waste metabolites in uremia by microencapsulated reactants. ASAIO J 15:353–358
Steele J, Hall J-P, Poncelet D, Neufeld R (2014) Therapeutic cell encapsulation techniques and applications in diabetes. Adv Drug Deliv Rev 67:74–83
Milton Van Dyke (1982) An album of fluid motion. The Parabolic Press. United States. ISBN: 0-915760-02-9
Park J, Chang H (2000) Microencapsulation of microbial cells. Biotechnol Adv 18:303–319
Zimmermann H, Shirley SG, Zimmermann U (2007) Alginate-based encapsulation of cells: past, present, and future. Curr Diab Rep 7:314–320
Jork A, Thürmer F, Cramer H, Zimmermann G, Gessner P, Hämel K, Hofmann G, Kuttler B, Hahn HJ, Josimovic-Alasevic O, Fritsch KG, Zimmermann U (2000) Biocompatible alginate from freshly collected Laminaria pallida for implantation. Appl Microbiol Biotechnol 53:224–229
Zimmermann U, Mimietz S, Zimmermann H, Hillgartner M, Schneider H, Ludwig J, Hasse C, Haase A, Rothmund M, Fuhr G (2000) Hydrogel-based non-autologous cell and tissue therapy. Biotechniques 29:564–581
Poncelet D, Neufeld R, Goosen M, Burgarski B, Babak V (1999) Formation of microgel beads by electric dispersion of polymer solutions. AIChE J 45:2018–2023
Ma M, Chiu A, Sahay G, Doloff JC, Dholakia N, Thakrar R, Cohen J, Vegas A, Chen D, Bratlie KM (2013) Core-shell hydrogel microcapsules for improved islets encapsulation. Adv Healthc Mater 2:667–672
Lu Y-C, Song W, An D, Kim BJ, Schwartz R, Wu M, Ma M (2014) Designing compartmentalized hydrogel microparticles for cell encapsulation and scalable 3D cell culture. J Mater Chem B 3:353. doi:10.1039/C4tb01735h
Serp D, Cantana E, Heinzen C, Von Stockar U, Marison I (2000) Characterization of an encapsulation device for the production of monodisperse alginate beads for cell immobilization. Biotechnol Bioeng 70:41–53
Prüße E, Jahnz, U, Wittlich P, Breford J, Vorlop K-D (2002) Bead production with jetcutting and rotating disc/nozzle technologies. Landbauforschung Völkenrode Sh 241:1–10
Strutt JW, Rayleigh L (1878) On the instability of jets. Proc London Math Soc 10:4–13
Tomei AA, Manzoli V, Fraker CA, Giraldo J, Velluto D, Najjar M, Pileggi A, Molano D, Ricordi C, Stabler CL, Hubbell JA (2014) Device design and materials optimization of conformal coating for islets of Langerhans. Proc Natl Acad Sci U S A 111:10514–10519. doi:10.1073/Pnas.1402216111
Tan WH, Takeuchi S (2007) Monodisperse alginate hydrogel microbeads for cell encapsulation. Adv Mater 19:2696–2701
Edd JF, Di Carlo D, Humphry KJ, Koester S, Irimia D, Weitz DA, Toner M (2008) Controlled encapsulation of single-cells into monodisperse picolitre drops. Lab Chip 8:1262–1264
Kim C, Chung S, Kim YE, Lee KS, Lee SH, Oh KW, Kang JY (2011) Generation of core-shell microcapsules with three-dimensional focusing device for efficient formation of cell spheroid. Lab Chip 11:246–252
Park D, Mun C, Kang E, No D, Ju J, Lee S (2014) One-stop microfiber spinning and fabrication of a fibrous cell-encapsulated scaffold on a single microfluidic platform. Biofabrication 6:024108
Puppi D, Dinucci D, Bartoli C, Mota C, Migone C, Dini F, Barsotti G, Carlucci F, Chiellini F (2011) Development of 3D wet-spun polymeric scaffolds loaded with antimicrobial agents for bone engineering. J Bioact Compat Polym 26:478–492
Kang E, Choi YY, Chae SK, Moon JH, Chang JY, Lee SH (2012) Microfluidic spinning of flat alginate fibers with grooves for cell‐aligning scaffolds. Adv Mater 24:4271–4277
Hwang CM, Khademhosseini A, Park Y, Sun K, Lee S-H (2008) Microfluidic chip-based fabrication of PLGA microfiber scaffolds for tissue engineering. Langmuir 24:6845–6851
Hwang C, Park Y, Park J, Lee K, Sun K, Khademhosseini A, Lee S (2009) Controlled cellular orientation on PLGA microfibers with defined diameters. Biomed Microdevices 11:739–746
Lee BR, Lee KH, Kang E, Kim D-S, Lee S-H (2011) Microfluidic wet spinning of chitosan-alginate microfibers and encapsulation of Hepg2 cells in fibers. Biomicrofluidics 5:022208
Lee KH, Shin SJ, Park Y, Lee SH (2009) Synthesis of cell‐laden alginate hollow fibers using microfluidic chips and microvascularized tissue‐engineering applications. Small 5:1264–1268
Jun Y, Kim MJ, Hwang YH, Jeon E, Kang AR, Lee S-H, Lee DY (2013) Microfluidics-generated pancreatic islet microfibers for enhanced immunoprotection. Biomaterials 34:8122–8130
Onoe H, Okitsu T, Itou A, Kato-Negishi M, Gojo R, Kiriya D, Sato K, Miura S, Iwanaga S, Kuribayashi-Shigetomi K (2013) Metre-long cell-laden microfibres exhibit tissue morphologies and functions. Nat Mater 12:584–590
An D, Ji Y, Chiu A, Lu Y-C, Song W, Zhai L, Qi L, Luo D, Ma M (2015) Developing robust, hydrogel-based, nanofiber-enabled encapsulation devices (needs) for cell therapies. Biomaterials 37:40–48
Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A (2010) Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 31:5536–5544
Koh W-G, Revzin A, Pishko MV (2002) Poly(ethylene glycol) hydrogel microstructures encapsulating living cells. Langmuir 18:2459–2462
Aubin H, Nichol JW, Hutson CB, Bae H, Sieminski AL, Cropek DM, Akhyari P, Khademhosseini A (2010) Directed 3D cell alignment and elongation in microengineered hydrogels. Biomaterials 31:6941–6951
Chung BG, Hatton TA (2008) Stop-flow lithography to generate cell-laden microgel particles. Lab Chip 8:1056–1061
Khademhosseini A, Eng G, Yeh J, Fukuda J, Blumling J, Langer R, Burdick JA (2006) Micromolding of photocrosslinkable hyaluronic acid for cell encapsulation and entrapment. J Biomed Mater Res A 79:522–532
Mcguigan AP, Bruzewicz DA, Glavan A, Butte M, Whitesides GM (2008) Cell encapsulation in sub-mm sized gel modules using replica molding. PLoS One 3, E2258
Matsunaga YT, Morimoto Y, Takeuchi S (2011) Molding cell beads for rapid construction of macroscopic 3D tissue architecture. Adv Mater 23:H90–H94
Poncelet D, Lencki R, Beaulieu C, Halle J, Neufeld R, Fournier A (1992) Production of alginate beads by emulsification/internal gelation. I. Methodology. Appl Microbiol Biotechnol 38:39–45
Hoesli CA, Raghuram K, Kiang RL, Mocinecová D, Hu X, Johnson JD, Lacík I, Kieffer TJ, Piret JM (2011) Pancreatic cell immobilization in alginate beads produced by emulsion and internal gelation. Biotechnol Bioeng 108:424–434
Hoesli CA, Kiang RL, Mocinecová D, Speck M, Mošková DJ, Donald-Hague C, Lacík I, Kieffer TJ, Piret JM (2012) Reversal of diabetes by βTC3 cells encapsulated in alginate beads generated by emulsion and internal gelation. J Biomed Mater Res B Appl Biomater 100:1017–1028
Krol S, Del Guerra S, Grupillo M, Diaspro A, Gliozzi A, Marchetti P (2006) Multilayer nanoencapsulation. New approach for immune protection of human pancreatic islets. Nano Lett 6:1933–1939
Miura S, Teramura Y, Iwata H (2006) Encapsulation of islets with ultra-thin polyion complex membrane through poly (ethylene glycol)-phospholipids anchored to cell membrane. Biomaterials 27:5828–5835
Contreras JL, Xie D, Mays J, Smyth CA, Eckstein C, Rahemtulla FG, Young CJ, Anthony Thompson J, Bilbao G, Curiel DT (2004) A novel approach to xenotransplantation combining surface engineering and genetic modification of isolated adult porcine islets. Surgery 136:537–547
Yun Lee D, Hee Nam J, Byun Y (2007) Functional and histological evaluation of transplanted pancreatic islets immunoprotected by pegylation and cyclosporine for 1 year. Biomaterials 28:1957–1966
Cruise GM, Hegre OD, Scharp DS, Hubbell JA (1998) A sensitivity study of the key parameters in the interfacial photopolymerization of poly (ethylene glycol) diacrylate upon porcine islets. Biotechnol Bioeng 57:655–665
Cruise GM, Scharp DS, Hubbell JA (1998) Characterization of permeability and network structure of interfacially photopolymerized poly (ethylene glycol) diacrylate hydrogels. Biomaterials 19:1287–1294
Cruise GM, Hegre OD, Lamberti FV, Hager SR, Hill R, Scharp DS, Hubbell JA (1998) In vitro and in vivo performance of porcine islets encapsulated in interfacially photopolymerized poly (ethylene glycol) diacrylate membranes. Cell Transplant 8:293–306
Teramura Y, Kaneda Y, Iwata H (2007) Islet-encapsulation in ultra-thin layer-by-layer membranes of poly (vinyl alcohol) anchored to poly (ethylene glycol)-lipids in the cell membrane. Biomaterials 28:4818–4825
Teramura Y, Oommen OP, Olerud J, Hilborn J, Nilsson B (2013) Microencapsulation of cells, including islets, within stable ultra-thin membranes of maleimide-conjugated PEG-lipid with multifunctional crosslinkers. Biomaterials 34:2683–2693
Wang T, Adcock J, Kühtreiber W, Qiang D, Salleng KJ, Trenary I, Williams P (2008) Successful allotransplantation of encapsulated islets in pancreatectomized canines for diabetic management without the use of immunosuppression. Transplantation 85:331–337
Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, Mckay R (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292:1389–1394
Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, Young H, Richardson M, Smart NG, Cunningham J (2008) Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 26:443–452
Dolgin E (2014) Encapsulate this. Nat Med 20:9–11
Nuttelman CR, Rice MA, Rydholm AE, Salinas CN, Shah DN, Anseth KS (2008) Macromolecular monomers for the synthesis of hydrogel niches and their application in cell encapsulation and tissue engineering. Prog Polym Sci 33:167–179
Orive G, Gascón AR, Hernández RM, Igartua M, Luis Pedraz J (2003) Cell microencapsulation technology for biomedical purposes: novel insights and challenges. Trends Pharmacol Sci 24:207–210
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Zhang, Y., Ma, M. (2016). Microscale Cell Encapsulation Materials and Fabrication Techniques for Type 1 Diabetes. In: Singh, A., Gaharwar, A. (eds) Microscale Technologies for Cell Engineering. Springer, Cham. https://doi.org/10.1007/978-3-319-20726-1_11
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