Comprehensive Physiology Wiley Online Library

Current State and Evidence of Cellular Encapsulation Strategies in Type 1 Diabetes

Full Article on Wiley Online Library



Abstract

Islet cell replacement therapies represent an effective way to restore physiologic glycemic control in patients with type 1 diabetes (T1DM) and severe hypoglycemia. Despite being able to provide long‐term insulin independence, patients still require lifelong immunosuppression, which has myriad detrimental effects including an increased risk for opportunistic infections and some types of cancer. This vital issue precludes widespread application of these therapies as a true cure for T1DM. Encapsulation of islets into immunoisolating/immunoprotective devices provides the potential of abrogating the requisite for lifelong immunosuppression. The field of cellular encapsulation lies at a complex intersection between the areas of chemistry, physics, bioengineering, cell biology, immunology, and clinical medicine. In diabetes, cellular encapsulation has existed for nearly 50 years, nevertheless, a resurgence of interest in the field has been motivated by promising results in small‐ and large‐animal models. Recent studies have demonstrated that long‐term diabetes reversal without immunosuppression is indeed routinely achievable. Future researchers interested in exploring cellular encapsulation strategies will require a clear understanding of the basic theoretical and practical principles, guiding this rapidly expanding field. This article will provide essential considerations concerning the physicochemical properties of the most commonly used biomaterials, relevant aspects of the immune response to bioencapsulation, current encapsulation strategies, potential implantation sites for encapsulated cell therapies and, finally, a comprehensive review on the current state of clinical translation. © 2020 American Physiological Society. Compr Physiol 10:839‐878, 2020.

Figure 1. Figure 1. MEDLINE/PubMed search for studies involving diabetes and cellular encapsulation (N = 1193).
Figure 2. Figure 2. Classical approaches for cellular encapsulation. Schematic representation of the two main approaches for cellular encapsulation: macro and microencapsulation.
Figure 3. Figure 3. Alternative and composite approaches for cellular encapsulation. Schematic representation of selected composite approaches for cellular encapsulation including nanofiber encapsulation, bioscaffolds, and drug‐eluting biomaterials.


Figure 1. MEDLINE/PubMed search for studies involving diabetes and cellular encapsulation (N = 1193).


Figure 2. Classical approaches for cellular encapsulation. Schematic representation of the two main approaches for cellular encapsulation: macro and microencapsulation.


Figure 3. Alternative and composite approaches for cellular encapsulation. Schematic representation of selected composite approaches for cellular encapsulation including nanofiber encapsulation, bioscaffolds, and drug‐eluting biomaterials.
References
 1.Abalovich A, Jatimliansky C, Diegex E, Arias M, Altamirano A, Amorena C, Martinez B, Nacucchio M. Pancreatic islets microencapsulation with polylactide‐co‐glycolide. Transplant Proc 33: 1977‐1979, 2001.
 2.American Diabetes A. Economic costs of diabetes in the U.S. in 2017. Diabetes Care 41: 917‐928, 2018.
 3.An D, Chiu A, Flanders JA, Song W, Shou D, Lu YC, Grunnet LG, Winkel L, Ingvorsen C, Christophersen NS, Fels JJ, Sand FW, Ji Y, Qi L, Pardo Y, Luo D, Silberstein M, Fan J, Ma M. Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes. Proc Natl Acad Sci USA 115: E263‐E272, 2018.
 4.Anselmo AC, McHugh KJ, Webster J, Langer R, Jaklenec A. Layer‐by‐layer encapsulation of probiotics for delivery to the microbiome. Adv Mater 28: 9486‐9490, 2016.
 5.Arifin DR, Valdeig S, Anders RA, Bulte JW, Weiss CR. Magnetoencapsulated human islets xenotransplanted into swine: A comparison of different transplantation sites. Xenotransplantation 23: 211‐221, 2016.
 6.Arzouni AA, Vargas‐Seymour A, Nardi N, A JFK, Jones PM. Using mesenchymal stromal cells in islet transplantation. Stem Cells Transl Med 7: 559‐563, 2018.
 7.Atkinson MA, von Herrath M, Powers AC, Clare‐Salzler M. Current concepts on the pathogenesis of type 1 diabetes—Considerations for attempts to prevent and reverse the disease. Diabetes Care 38: 979‐988, 2015.
 8.Avgoustiniatos ES, Colton CK. Effect of external oxygen mass transfer resistances on viability of immunoisolated tissue. Ann N Y Acad Sci 831: 145‐167, 1997.
 9.Azadi SA, Vasheghani‐Farahani E, Hashemi‐Najafbabadi S, Godini A. Co‐encapsulation of pancreatic islets and pentoxifylline in alginate‐based microcapsules with enhanced immunosuppressive effects. Prog Biomater 5: 101‐109, 2016.
 10.Azzi J, Geara AS, El‐Sayegh S, Abdi R. Immunological aspects of pancreatic islet cell transplantation. Expert Rev Clin Immunol 6: 111‐124, 2010.
 11.Baidal DA, Ricordi C, Berman DM, Alvarez A, Padilla N, Ciancio G, Linetsky E, Pileggi A, Alejandro R. Bioengineering of an intraabdominal endocrine pancreas. N Engl J Med 376: 1887‐1889, 2017.
 12.Balamurugan AN, Gu Y, Tabata Y, Miyamoto M, Cui W, Hori H, Satake A, Nagata N, Wang W, Inoue K. Bioartificial pancreas transplantation at prevascularized intermuscular space: Effect of angiogenesis induction on islet survival. Pancreas 26: 279‐285, 2003.
 13.Barkai U, Rotem A, de Vos P. Survival of encapsulated islets: More than a membrane story. World J Transplant 6: 69‐90, 2016.
 14.Barkai U, Weir GC, Colton CK, Ludwig B, Bornstein SR, Brendel MD, Neufeld T, Bremer C, Leon A, Evron Y, Yavriyants K, Azarov D, Zimermann B, Maimon S, Shabtay N, Balyura M, Rozenshtein T, Vardi P, Bloch K, de Vos P, Rotem A. Enhanced oxygen supply improves islet viability in a new bioartificial pancreas. Cell Transplant 22: 1463‐1476, 2013.
 15.Barrett KE, Barman SM, Boitano S, Brooks HL, editors. Ganong's Review of Medical Physiology (25th ed). New York, NY: McGraw‐Hill Education, 2018.
 16.Bartholomeus K, Jacobs‐Tulleneers‐Thevissen D, Shouyue S, Suenens K, In't Veld PA, Pipeleers‐Marichal M, Pipeleers DG, Hellemans K. Omentum is better site than kidney capsule for growth, differentiation, and vascularization of immature porcine beta‐cell implants in immunodeficient rats. Transplantation 96: 1026‐1033, 2013.
 17.Basta G, Montanucci P, Luca G, Boselli C, Noya G, Barbaro B, Qi M, Kinzer KP, Oberholzer J, Calafiore R. Long‐term metabolic and immunological follow‐up of nonimmunosuppressed patients with type 1 diabetes treated with microencapsulated islet allografts: Four cases. Diabetes Care 34: 2406‐2409, 2011.
 18.Bekiari E, Kitsios K, Thabit H, Tauschmann M, Athanasiadou E, Karagiannis T, Haidich AB, Hovorka R, Tsapas A. Artificial pancreas treatment for outpatients with type 1 diabetes: Systematic review and meta‐analysis. BMJ 361: k1310, 2018.
 19.Bellin MD, Barton FB, Heitman A, Harmon JV, Kandaswamy R, Balamurugan AN, Sutherland DE, Alejandro R, Hering BJ. Potent induction immunotherapy promotes long‐term insulin independence after islet transplantation in type 1 diabetes. Am J Transplant 12: 1576‐1583, 2012.
 20.Berney T, Buhler LH, Majno P, Mentha G, Morel P. Immunosuppression for pancreatic islet transplantation. Transplant Proc 36: 362S‐366S, 2004.
 21.Bertuzzi F, Colussi G, Lauterio A, De Carlis L. Intramuscular islet allotransplantation in type 1 diabetes mellitus. Eur Rev Med Pharmacol Sci 22: 1731‐1736, 2018.
 22.Bhujbal SV, Paredes‐Juarez GA, Niclou SP, de Vos P. Factors influencing the mechanical stability of alginate beads applicable for immunoisolation of mammalian cells. J Mech Behav Biomed Mater 37: 196‐208, 2014.
 23.Blake DF, Young DA, Brown LH. Transcutaneous oximetry: Variability in normal values for the upper and lower limb. Diving Hyperb Med 48: 2‐9, 2018.
 24.Bochenek M. Immuno‐isolation strategies for islet transplantation into rodent and non‐human primate models. In: Department of Bioengineering. Chicago, IL, U.S.A., University of Illinois at Chicago, 2015, p. 166.
 25.Bochenek MA, Veiseh O, Vegas AJ, McGarrigle JJ, Qi M, Marchese E, Omami M, Doloff JC, Mendoza‐Elias J, Nourmohammadzadeh M, Khan A, Yeh CC, Xing Y, Isa D, Ghani S, Li J, Landry C, Bader AR, Olejnik K, Chen M, Hollister‐Lock J, Wang Y, Greiner DL, Weir GC, Strand BL, Rokstad AMA, Lacik I, Langer R, Anderson DG, Oberholzer J. Alginate encapsulation as long‐term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques. Nat Biomed Eng 2: 810‐821, 2018.
 26.Borg DJ, Bonifacio E. The use of biomaterials in islet transplantation. Curr Diab Rep 11: 434‐444, 2011.
 27.Boyko EJ, Ahroni JH, Stensel VL. Tissue oxygenation and skin blood flow in the diabetic foot: Responses to cutaneous warming. Foot Ankle Int 22: 711‐714, 2001.
 28.Brauker JH, Carr‐Brendel VE, Martinson LA, Crudele J, Johnston WD, Johnson RC. Neovascularization of synthetic membranes directed by membrane microarchitecture. J Biomed Mater Res 29: 1517‐1524, 1995.
 29.Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ III, Anderson SM, Church MM, Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW, iDCL Trial Research Group. Six‐month randomized, multicenter trial of closed‐loop control in type 1 diabetes. N Engl J Med 381: 1707‐1717, 2019.
 30.Buchwald P, Tamayo‐Garcia A, Manzoli V, Tomei AA, Stabler CL. Glucose‐stimulated insulin release: Parallel perifusion studies of free and hydrogel encapsulated human pancreatic islets. Biotechnol Bioeng 115: 232‐245, 2018.
 31.Bunger CM, Tiefenbach B, Jahnke A, Gerlach C, Freier T, Schmitz KP, Hopt UT, Schareck W, Klar E, de Vos P. Deletion of the tissue response against alginate‐pll capsules by temporary release of co‐encapsulated steroids. Biomaterials 26: 2353‐2360, 2005.
 32.Calafiore R. Transplantation of microencapsulated pancreatic human islets for therapy of diabetes mellitus. A preliminary report. ASAIO J 38: 34‐37, 1992.
 33.Calafiore R, Basta G, Luca G, Boselli C, Bufalari A, Bufalari A, Cassarani MP, Giustozzi GM, Brunetti P. Transplantation of pancreatic islets contained in minimal volume microcapsules in diabetic high mammalians. Ann N Y Acad Sci 875: 219‐232, 1999.
 34.Calafiore R, Basta G, Luca G, Lemmi A, Montanucci MP, Calabrese G, Racanicchi L, Mancuso F, Brunetti P. Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: First two cases. Diabetes Care 29: 137‐138, 2006.
 35.Calafiore R, Luca G, Calvitti M, Neri LM, Basta G, Capitani S, Becchetti E, Brunetti P. Cellular support systems for alginate microcapsules containing islets, as composite bioartificial pancreas. Ann N Y Acad Sci 944: 240‐251, 2001.
 36.Cantarelli E, Piemonti L. Alternative transplantation sites for pancreatic islet grafts. Curr Diab Rep 11: 364‐374, 2011.
 37.Carlsson PO, Espes D, Sedigh A, Rotem A, Zimerman B, Grinberg H, Goldman T, Barkai U, Avni Y, Westermark GT, Carlbom L, Ahlstrom H, Eriksson O, Olerud J, Korsgren O. Transplantation of macroencapsulated human islets within the bioartificial pancreas betaAir to patients with type 1 diabetes mellitus. Am J Transplant 18: 1735‐1744, 2018.
 38.Chang R, Faleo G, Russ HA, Parent AV, Elledge SK, Bernards DA, Allen JL, Villanueva K, Hebrok M, Tang Q, Desai TA. Nanoporous immunoprotective device for stem‐cell‐derived beta‐cell replacement therapy. ACS Nano 11: 7747‐7757, 2017.
 39.Chen T, Yuan J, Duncanson S, Hibert ML, Kodish BC, Mylavaganam G, Maker M, Li H, Sremac M, Santosuosso M, Forbes B, Kashiwagi S, Cao J, Lei J, Thomas M, Hartono C, Sachs D, Markmann J, Sambanis A, Poznansky MC. Alginate encapsulant incorporating CXCL12 supports long‐term allo‐ and xenoislet transplantation without systemic immune suppression. Am J Transplant 15: 618‐627, 2015.
 40.Chick WL, Perna JJ, Lauris V, Low D, Galletti PM, Panol G, Whittemore AD, Like AA, Colton CK, Lysaght MJ. Artificial pancreas using living beta cells: Effects on glucose homeostasis in diabetic rats. Science 197: 780‐782, 1977.
 41.Choudhary P, Rickels MR, Senior PA, Vantyghem MC, Maffi P, Kay TW, Keymeulen B, Inagaki N, Saudek F, Lehmann R, Hering BJ. Evidence‐informed clinical practice recommendations for treatment of type 1 diabetes complicated by problematic hypoglycemia. Diabetes Care 38: 1016‐1029, 2015.
 42.Christoffersson G, Henriksnas J, Johansson L, Rolny C, Ahlstrom H, Caballero‐Corbalan J, Segersvard R, Permert J, Korsgren O, Carlsson PO, Phillipson M. Clinical and experimental pancreatic islet transplantation to striated muscle: Establishment of a vascular system similar to that in native islets. Diabetes 59: 2569‐2578, 2010.
 43.CITR . Tenth Annual Report Collaborative Islet Transplant Registry, 2017.
 44.Conget I, Avila D, Gimenez M, Quiros C, Salaverria V, Duenas B. Impaired awareness of hypoglycaemia in subjects with type 1 diabetes. Results of an online survey in a diabetes web site. Endocrinol Nutr 63: 121‐125, 2016.
 45.Cook PS, Kendall G, Michael M, Brown N. The textures of globalization: Biopolitics and the closure of xenotourism. New Genet Soc 30: 101‐114, 2011.
 46.Correia CR, Pirraco RP, Cerqueira MT, Marques AP, Reis RL, Mano JF. Semipermeable capsules wrapping a multifunctional and self‐regulated co‐culture microenvironment for osteogenic differentiation. Sci Rep 6: 21883, 2016.
 47.Costa RR, Alatorre‐Meda M, Mano JF. Drug nano‐reservoirs synthesized using layer‐by‐layer technologies. Biotechnol Adv 33: 1310‐1326, 2015.
 48.Dadheech N, James Shapiro AM. Human induced pluripotent stem cells in the curative treatment of diabetes and potential impediments ahead. Adv Exp Med Biol 1144: 25‐35, 2019.
 49.Dang TT, Thai AV, Cohen J, Slosberg JE, Siniakowicz K, Doloff JC, Ma M, Hollister‐Lock J, Tang KM, Gu Z, Cheng H, Weir GC, Langer R, Anderson DG. Enhanced function of immuno‐isolated islets in diabetes therapy by co‐encapsulation with an anti‐inflammatory drug. Biomaterials 34: 5792‐5801, 2013.
 50.Daum N, Neumeyer A, Wahl B, Bur M, Lehr CM. In vitro systems for studying epithelial transport of macromolecules. Methods Mol Biol 480: 151‐164, 2009.
 51.De Mesmaeker I, Robert T, Suenens KG, Stange GM, Van Hulle F, Ling Z, Tomme P, Jacobs‐Tulleneers‐Thevissen D, Keymeulen B, Pipeleers DG. Increase functional beta‐cell mass in subcutaneous alginate capsules with porcine prenatal islet cells but loss with human adult islet cells. Diabetes 67: 2640‐2649, 2018.
 52.de Vos P, Bucko M, Gemeiner P, Navratil M, Svitel J, Faas M, Strand BL, Skjak‐Braek G, Morch YA, Vikartovska A, Lacik I, Kollarikova G, Orive G, Poncelet D, Pedraz JL, Ansorge‐Schumacher MB. Multiscale requirements for bioencapsulation in medicine and biotechnology. Biomaterials 30: 2559‐2570, 2009.
 53.de Vos P, Faas MM, Strand B, Calafiore R. Alginate‐based microcapsules for immunoisolation of pancreatic islets. Biomaterials 27: 5603‐5617, 2006.
 54.De Vos P, Vegter D, De Haan BJ, Strubbe JH, Bruggink JE, Van Schilfgaarde R. Kinetics of intraperitoneally infused insulin in rats. Functional implications for the bioartificial pancreas. Diabetes 45: 1102‐1107, 1996.
 55.Douglas JA, Sefton MV. The permeability of EUDRAGIT RL and HEMA‐MMA microcapsules to glucose and inulin. Biotechnol Bioeng 36: 653‐664, 1990.
 56.Dufour JM, Rajotte RV, Zimmerman M, Rezania A, Kin T, Dixon DE, Korbutt GS. Development of an ectopic site for islet transplantation, using biodegradable scaffolds. Tissue Eng 11: 1323‐1331, 2005.
 57.Dufrane D, Goebbels RM, Saliez A, Guiot Y, Gianello P. Six‐month survival of microencapsulated pig islets and alginate biocompatibility in primates: Proof of concept. Transplantation 81: 1345‐1353, 2006.
 58.Dufrane D, Steenberghe M, Goebbels RM, Saliez A, Guiot Y, Gianello P. The influence of implantation site on the biocompatibility and survival of alginate encapsulated pig islets in rats. Biomaterials 27: 3201‐3208, 2006.
 59.Duvivier‐Kali VF, Omer A, Parent RJ, O'Neil JJ, Weir GC. Complete protection of islets against allorejection and autoimmunity by a simple barium‐alginate membrane. Diabetes 50: 1698‐1705, 2001.
 60.Elliott RB, Escobar L, Tan PL, Muzina M, Zwain S, Buchanan C. Live encapsulated porcine islets from a type 1 diabetic patient 9.5 yr after xenotransplantation. Xenotransplantation 14: 157‐161, 2007.
 61.Ernst AU, Bowers DT, Wang LH, Shariati K, Plesser MD, Brown NK, Mehrabyan T, Ma M. Nanotechnology in cell replacement therapies for type 1 diabetes. Adv Drug Deliv Rev 139: 116‐138, 2019.
 62.Ernst AU, Wang LH, Ma M. Interconnected toroidal hydrogels for islet encapsulation. Adv Healthc Mater 8: e1900423, 2019.
 63.Ernst AU, Wang L‐H, Ma M. Islet encapsulation. J Mater Chem B 6: 6705‐6722, 2018.
 64.Espona‐Noguera A, Ciriza J, Canibano‐Hernandez A, Villa R, Saenz Del Burgo L, Alvarez M, Luis Pedraz J. 3D printed polyamide macroencapsulation devices combined with alginate hydrogels for insulin‐producing cell‐based therapies. Int J Pharm 566: 604‐614, 2019.
 65.Farah S, Doloff JC, Muller P, Sadraei A, Han HJ, Olafson K, Vyas K, Tam HH, Hollister‐Lock J, Kowalski PS, Griffin M, Meng A, McAvoy M, Graham AC, McGarrigle J, Oberholzer J, Weir GC, Greiner DL, Langer R, Anderson DG. Long‐term implant fibrosis prevention in rodents and non‐human primates using crystallized drug formulations. Nat Mater 18: 892‐904, 2019.
 66.Farney AC, Najarian JS, Nakhleh RE, Lloveras G, Field MJ, Gores PF, Sutherland DE. Autotransplantation of dispersed pancreatic islet tissue combined with total or near‐total pancreatectomy for treatment of chronic pancreatitis. Surgery 110: 427‐437; discussion 437‐429, 1991.
 67.Ferguson J, Scothorne RJ. Further studies on the transplantation of isolated pancreatic islets. J Anat 124: 9‐20, 1977.
 68.Foster GA, Garcia AJ. Bio‐synthetic materials for immunomodulation of islet transplants. Adv Drug Deliv Rev 114: 266‐271, 2017.
 69.Fukuda S, Yabe SG, Nishida J, Takeda F, Nashiro K, Okochi H. The intraperitoneal space is more favorable than the subcutaneous one for transplanting alginate fiber containing iPS‐derived islet‐like cells. Regen Ther 11: 65‐72, 2019.
 70.Fung M, Thompson D, Shapiro RJ, Warnock GL, Andersen DK, Elahi D, Meneilly GS. Effect of glucagon‐like peptide‐1 (7‐37) on beta‐cell function after islet transplantation in type 1 diabetes. Diabetes Res Clin Pract 74: 189‐193, 2006.
 71.Galisova A, Fabryova E, Sticova E, Kosinova L, Jiratova M, Herynek V, Berkova Z, Kriz J, Hajek M, Jirak D. The optimal timing for pancreatic islet transplantation into subcutaneous scaffolds assessed by multimodal imaging. Contrast Media Mol Imaging 2017: 5418495, 2017.
 72.Garcia‐Alonso J, Fakhrullin RF, Paunov VN, Shen Z, Hardege JD, Pamme N, Haswell SJ, Greenway GM. Microscreening toxicity system based on living magnetic yeast and gradient chips. Anal Bioanal Chem 400: 1009‐1013, 2011.
 73.Gimi B, Kwon J, Kuznetsov A, Vachha B, Magin RL, Philipson LH, Lee JB. A nanoporous, transparent microcontainer for encapsulated islet therapy. J Diabetes Sci Technol 3: 297‐303, 2009.
 74.Graham JG, Zhang X, Goodman A, Pothoven K, Houlihan J, Wang S, Gower RM, Luo X, Shea LD. PLG scaffold delivered antigen‐specific regulatory T cells induce systemic tolerance in autoimmune diabetes. Tissue Eng Part A 19: 1465‐1475, 2013.
 75.Gray DW. An overview of the immune system with specific reference to membrane encapsulation and islet transplantation. Ann N Y Acad Sci 944: 226‐239, 2001.
 76.Gwon SH, Yoon J, Seok HK, Oh KH, Sun J‐Y. Gelation dynamics of ionically crosslinked alginate gel with various cations. Macromol Res 23: 1112‐1116, 2015.
 77.Hashemi M, Kalalinia F. Application of encapsulation technology in stem cell therapy. Life Sci 143: 139‐146, 2015.
 78.Headen DM, Woodward KB, Coronel MM, Shrestha P, Weaver JD, Zhao H, Tan M, Hunckler MD, Bowen WS, Johnson CT, Shea L, Yolcu ES, Garcia AJ, Shirwan H. Local immunomodulation Fas ligand‐engineered biomaterials achieves allogeneic islet graft acceptance. Nat Mater 17: 732‐739, 2018.
 79.Hicks G, George R, Sywak M. Short and long‐term impact of parathyroid autotransplantation on parathyroid function after total thyroidectomy. Gland Surg 6: S75‐S85, 2017.
 80.Hill RS, Cruise GM, Hager SR, Lamberti FV, Yu X, Garufis CL, Yu Y, Mundwiler KE, Cole JF, Hubbell JA, Hegre OD, Scharp DW. Immunoisolation of adult porcine islets for the treatment of diabetes mellitus. The use of photopolymerizable polyethylene glycol in the conformal coating of mass‐isolated porcine islets. Ann N Y Acad Sci 831: 332‐343, 1997.
 81.Hoesli CA, Luu M, Piret JM. A novel alginate hollow fiber bioreactor process for cellular therapy applications. Biotechnol Prog 25: 1740‐1751, 2009.
 82.Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab 287: E199‐E206, 2004.
 83.Hook AL, Anderson DG, Langer R, Williams P, Davies MC, Alexander MR. High throughput methods applied in biomaterial development and discovery. Biomaterials 31: 187‐198, 2010.
 84.Hu S, de Vos P. Polymeric approaches to reduce tissue responses against devices applied for islet‐cell encapsulation. Front Bioeng Biotechnol 7: 134, 2019.
 85.Jacobs‐Tulleneers‐Thevissen D, Chintinne M, Ling Z, Gillard P, Schoonjans L, Delvaux G, Strand BL, Gorus F, Keymeulen B, Pipeleers D, Beta Cell Therapy Consortium EU‐FP7. Sustained function of alginate‐encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient. Diabetologia 56: 1605‐1614, 2013.
 86.Jafari M, Paknejad Z, Rad MR, Motamedian SR, Eghbal MJ, Nadjmi N, Khojasteh A. Polymeric scaffolds in tissue engineering: A literature review. J Biomed Mater Res B Appl Biomater 105: 431‐459, 2017.
 87.Jansson L, Barbu A, Bodin B, Drott CJ, Espes D, Gao X, Grapensparr L, Kallskog O, Lau J, Liljeback H, Palm F, Quach M, Sandberg M, Stromberg V, Ullsten S, Carlsson PO. Pancreatic islet blood flow and its measurement. Ups J Med Sci 121: 81‐95, 2016.
 88.Jindal RM, Sidner RA, McDaniel HB, Johnson MS, Fineberg SE. Intraportal vs kidney subcapsular site for human pancreatic islet transplantation. Transplant Proc 30: 398‐399, 1998.
 89.Johnson JD, Ao Z, Ao P, Li H, Dai LJ, He Z, Tee M, Potter KJ, Klimek AM, Meloche RM, Thompson DM, Verchere CB, Warnock GL. Different effects of FK506, rapamycin, and mycophenolate mofetil on glucose‐stimulated insulin release and apoptosis in human islets. Cell Transplant 18: 833‐845, 2009.
 90.Kanick SC, Schneider PA, Klitzman B, Wisniewski NA, Rebrin K. Continuous monitoring of interstitial tissue oxygen using subcutaneous oxygen microsensors: In vivo characterization in healthy volunteers. Microvasc Res 124: 6‐18, 2019.
 91.Kawahara T, Kin T, Kashkoush S, Gala‐Lopez B, Bigam DL, Kneteman NM, Koh A, Senior PA, Shapiro AM. Portal vein thrombosis is a potentially preventable complication in clinical islet transplantation. Am J Transplant 11: 2700‐2707, 2011.
 92.Kemp CB, Knight MJ, Scharp DW, Ballinger WF, Lacy PE. Effect of transplantation site on the results of pancreatic islet isografts in diabetic rats. Diabetologia 9: 486‐491, 1973.
 93.Kessler L, Aprahamian M, Keipes M, Damge C, Pinget M, Poinsot D. Diffusion properties of an artificial membrane used for Langerhans islets encapsulation: An in vitro test. Biomaterials 13: 44‐49, 1992.
 94.Kim HI, Yu JE, Park CG, Kim SJ. Comparison of four pancreatic islet implantation sites. J Korean Med Sci 25: 203‐210, 2010.
 95.Korbutt GS, Elliott JF, Ao Z, Smith DK, Warnock GL, Rajotte RV. Large scale isolation, growth, and function of porcine neonatal islet cells. J Clin Invest 97: 2119‐2129, 1996.
 96.Korsgren O. Islet encapsulation: Physiological possibilities and limitations. Diabetes 66: 1748‐1754, 2017.
 97.Kozlovskaya V, Xue B, Lei W, Padgett LE, Tse HM, Kharlampieva E. Hydrogen‐bonded multilayers of tannic acid as mediators of T‐cell immunity. Adv Healthc Mater 4: 686‐694, 2015.
 98.Kozlovskaya V, Zavgorodnya O, Chen Y, Ellis K, Tse HM, Cui W, Thompson JA, Kharlampieva E. Ultrathin polymeric coatings based on hydrogen‐bonded polyphenol for protection of pancreatic islet cells. Adv Funct Mater 22: 3389‐3398, 2012.
 99.Krishnamurthy NV, Gimi B. Encapsulated cell grafts to treat cellular deficiencies and dysfunction. Crit Rev Biomed Eng 39: 473‐491, 2011.
 100.Krishnan R, Alexander M, Robles L, Foster CE, Lakey JR. Islet and stem cell encapsulation for clinical transplantation. Rev Diabet Stud 11: 84‐101, 2014.
 101.Kriz J, Vilk G, Mazzuca DM, Toleikis PM, Foster PJ, White DJ. A novel technique for the transplantation of pancreatic islets within a vascularized device into the greater omentum to achieve insulin independence. Am J Surg 203: 793‐797, 2012.
 102.Krol S, del Guerra S, Grupillo M, Diaspro A, Gliozzi A, Marchetti P. Multilayer nanoencapsulation. New approach for immune protection of human pancreatic islets. Nano Lett 6: 1933‐1939, 2006.
 103.Kronenberg H, Williams RH. Williams Textbook of Endocrinology. Philadelphia: Saunders/Elsevier, 2008, p. xix, 1911 p.
 104.Kumagai‐Braesch M, Jacobson S, Mori H, Jia X, Takahashi T, Wernerson A, Flodstrom‐Tullberg M, Tibell A. The TheraCyte device protects against islet allograft rejection in immunized hosts. Cell Transplant 22: 1137‐1146, 2013.
 105.Kumbar S, Laurencin C, Deng M. Natural and Synthetic Biomedical Polymers. Amsterdam; Boston: Elsevier, 2014, p. xvii, 402 pages.
 106.Lanza RP, Borland KM, Lodge P, Carretta M, Sullivan SJ, Muller TE, Solomon BA, Maki T, Monaco AP, Chick WL. Treatment of severely diabetic pancreatectomized dogs using a diffusion‐based hybrid pancreas. Diabetes 41: 886‐889, 1992.
 107.Latres E, Finan DA, Greenstein JL, Kowalski A, Kieffer TJ. Navigating two roads to glucose normalization in diabetes: Automated insulin delivery devices and cell therapy. Cell Metab 29: 545‐563, 2019.
 108.Lee SH, Hao E, Savinov AY, Geron I, Strongin AY, Itkin‐Ansari P. Human beta‐cell precursors mature into functional insulin‐producing cells in an immunoisolation device: Implications for diabetes cell therapies. Transplantation 87: 983‐991, 2009.
 109.Li X, Meng Q, Zhang L. The fate of allogeneic pancreatic islets following intraportal transplantation: Challenges and solutions. J Immunol Res 2018: 2424586, 2018.
 110.Lim F, Sun AM. Microencapsulated islets as bioartificial endocrine pancreas. Science 210: 908‐910, 1980.
 111.Lin CC, Metters AT, Anseth KS. Functional PEG‐peptide hydrogels to modulate local inflammation induced by the pro‐inflammatory cytokine TNFalpha. Biomaterials 30: 4907‐4914, 2009.
 112.Liu G, Li L, Huo D, Li Y, Wu Y, Zeng L, Cheng P, Xing M, Zeng W, Zhu C. A VEGF delivery system targeting MI improves angiogenesis and cardiac function based on the tropism of MSCs and layer‐by‐layer self‐assembly. Biomaterials 127: 117‐131, 2017.
 113.Liu JMH, Zhang J, Zhang X, Hlavaty KA, Ricci CF, Leonard JN, Shea LD, Gower RM. Transforming growth factor‐beta 1 delivery from microporous scaffolds decreases inflammation post‐implant and enhances function of transplanted islets. Biomaterials 80: 11‐19, 2016.
 114.Liu T, Wang Y, Zhong W, Li B, Mequanint K, Luo G, Xing M. Biomedical applications of layer‐by‐layer self‐assembly for cell encapsulation: Current status and future perspectives. Adv Healthc Mater 8: e1800939, 2019.
 115.Ludwig B, Reichel A, Steffen A, Zimerman B, Schally AV, Block NL, Colton CK, Ludwig S, Kersting S, Bonifacio E, Solimena M, Gendler Z, Rotem A, Barkai U, Bornstein SR. Transplantation of human islets without immunosuppression. Proc Natl Acad Sci U S A 110: 19054‐19058, 2013.
 116.Ludwig B, Rotem A, Schmid J, Weir GC, Colton CK, Brendel MD, Neufeld T, Block NL, Yavriyants K, Steffen A, Ludwig S, Chavakis T, Reichel A, Azarov D, Zimermann B, Maimon S, Balyura M, Rozenshtein T, Shabtay N, Vardi P, Bloch K, de Vos P, Schally AV, Bornstein SR, Barkai U. Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist. Proc Natl Acad Sci U S A 109: 5022‐5027, 2012.
 117.Lukinius A, Jansson L, Korsgren O. Ultrastructural evidence for blood microvessels devoid of an endothelial cell lining in transplanted pancreatic islets. Am J Pathol 146: 429‐435, 1995.
 118.Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R. Differentiation of embryonic stem cells to insulin‐secreting structures similar to pancreatic islets. Science 292: 1389‐1394, 2001.
 119.Maitz M. Applications of synthetic polymers in clinical medicine. Biosurf Biotribol 1: 161‐176, 2015.
 120.Maki T, Ubhi CS, Sanchez‐Farpon H, Sullivan SJ, Borland K, Muller TE, Solomon BA, Chick WL, Monaco AP. Successful treatment of diabetes with the biohybrid artificial pancreas in dogs. Transplantation 51: 43‐51, 1991.
 121.Mariani E, Lisignoli G, Borzi RM, Pulsatelli L. Biomaterials: Foreign bodies or tuners for the immune response? Int J Mol Sci 20, 2019. DOI: 10.3390/ijms20030636.
 122.Martinsen A, Skjak‐Braek G, Smidsrod O. Alginate as immobilization material: I. Correlation between chemical and physical properties of alginate gel beads. Biotechnol Bioeng 33: 79‐89, 1989.
 123.Martin‐Timon I, Del Canizo‐Gomez FJ. Mechanisms of hypoglycemia unawareness and implications in diabetic patients. World J Diabetes 6: 912‐926, 2015.
 124.Matlaga BF, Yasenchak LP, Salthouse TN. Tissue response to implanted polymers: The significance of sample shape. J Biomed Mater Res 10: 391‐397, 1976.
 125.Matsumoto S, Abalovich A, Wechsler C, Wynyard S, Elliott RB. Clinical benefit of islet xenotransplantation for the treatment of type 1 diabetes. EBioMedicine 12: 255‐262, 2016.
 126.Matsumoto S, Tan P, Baker J, Durbin K, Tomiya M, Azuma K, Doi M, Elliott RB. Clinical porcine islet xenotransplantation under comprehensive regulation. Transplant Proc 46: 1992‐1995, 2014.
 127.Merani S, Toso C, Emamaullee J, Shapiro AM. Optimal implantation site for pancreatic islet transplantation. Br J Surg 95: 1449‐1461, 2008.
 128.von Mering J, Minkowski O. Diabetes mellitus naeh Pankreasexstirpation. Archiv für experimentelle Pathologie und Pharmakologie 26: 371‐387, 1890.
 129.Monaco AP, Maki T, Ozato H, Carretta M, Sullivan SJ, Borland KM, Mahoney MD, Chick WL, Muller TE, Wolfrum J, Solomon B. Transplantation of islet allografts and xenografts in totally pancreatectomized diabetic dogs using the hybrid artificial pancreas. Ann Surg 214: 339‐360; discussion 361‐332, 1991.
 130.Morch YA, Qi M, Gundersen PO, Formo K, Lacik I, Skjak‐Braek G, Oberholzer J, Strand BL. Binding and leakage of barium in alginate microbeads. J Biomed Mater Res A 100: 2939‐2947, 2012.
 131.Moucheraud C, Lenz C, Latkovic M, Wirtz VJ. The costs of diabetes treatment in low‐ and middle‐income countries: A systematic review. BMJ Glob Health 4: e001258, 2019.
 132.Neoh KG, Li M, Kang E‐T, Chiong E, Tambyah PA. Surface modification strategies for combating catheter‐related complications: Recent advances and challenges. J Mater Chem B 5: 2045‐2067, 2017.
 133.Nishiguchi A, Yoshida H, Matsusaki M, Akashi M. Rapid construction of three‐dimensional multilayered tissues with endothelial tube networks by the cell‐accumulation technique. Adv Mater 23: 3506‐3510, 2011.
 134.Nyitray CE, Chang R, Faleo G, Lance KD, Bernards DA, Tang Q, Desai TA. Polycaprolactone thin‐film micro‐ and nanoporous cell‐encapsulation devices. ACS Nano 9: 5675‐5682, 2015.
 135.Olabisi RM. Cell microencapsulation with synthetic polymers. J Biomed Mater Res A 103: 846‐859, 2015.
 136.Oliveira MB, Mano JF. High‐throughput screening for integrative biomaterials design: Exploring advances and new trends. Trends Biotechnol 32: 627‐636, 2014.
 137.Onoe H, Okitsu T, Itou A, Kato‐Negishi M, Gojo R, Kiriya D, Sato K, Miura S, Iwanaga S, Kuribayashi‐Shigetomi K, Matsunaga YT, Shimoyama Y, Takeuchi S. Metre‐long cell‐laden microfibres exhibit tissue morphologies and functions. Nat Mater 12: 584‐590, 2013.
 138.Oram RA, Sims EK, Evans‐Molina C. Beta cells in type 1 diabetes: Mass and function; sleeping or dead? Diabetologia 62: 567‐577, 2019.
 139.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 22: 87‐92, 2004.
 140.Orive G, Santos E, Pedraz JL, Hernandez RM. Application of cell encapsulation for controlled delivery of biological therapeutics. Adv Drug Deliv Rev 67‐68: 3‐14, 2014.
 141.Ortiz‐Prado E, Dunn JF, Vasconez J, Castillo D, Viscor G. Partial pressure of oxygen in the human body: A general review. Am J Blood Res 9: 1‐14, 2019.
 142.O'Sullivan ES, Vegas A, Anderson DG, Weir GC. Islets transplanted in immunoisolation devices: A review of the progress and the challenges that remain. Endocr Rev 32: 827‐844, 2011.
 143.Park H, Haque MR, Park JB, Lee KW, Lee S, Kwon Y, Lee HS, Kim GS, Shin DY, Jin SM, Kim JH, Kang HJ, Byun Y, Kim SJ. Polymeric nano‐shielded islets with heparin‐polyethylene glycol in a non‐human primate model. Biomaterials 171: 164‐177, 2018.
 144.Pathiraja V, Villani V, Tasaki M, Matar AJ, Duran‐Struuck R, Yamada R, Moran SG, Clayman ES, Hanekamp J, Shimizu A, Sachs DH, Huang CA, Yamada K. Tolerance of vascularized islet‐kidney transplants in rhesus monkeys. Am J Transplant 17: 91‐102, 2017.
 145.Pedraza E, Coronel MM, Fraker CA, Ricordi C, Stabler CL. Preventing hypoxia‐induced cell death in beta cells and islets via hydrolytically activated, oxygen‐generating biomaterials. Proc Natl Acad Sci U S A 109: 4245‐4250, 2012.
 146.Pellicciaro M, Vella I, Lanzoni G, Tisone G, Ricordi C. The greater omentum as a site for pancreatic islet transplantaion. CellR4 5: e2410, 2017.
 147.Pepper AR, Gala‐Lopez B, Pawlick R, Merani S, Kin T, Shapiro AM. A prevascularized subcutaneous device‐less site for islet and cellular transplantation. Nat Biotechnol 33: 518‐523, 2015.
 148.Pepper AR, Pawlick R, Bruni A, Gala‐Lopez B, Wink J, Rafiei Y, Bral M, Abualhassan N, Shapiro AM. Harnessing the Foreign body reaction in marginal mass device‐less subcutaneous islet transplantation in mice. Transplantation 100: 1474‐1479, 2016.
 149.Petruzzo P, Pibiri L, De Giudici MA, Basta G, Calafiore R, Falorni A, Brunetti P, Brotzu G. Xenotransplantation of microencapsulated pancreatic islets contained in a vascular prosthesis: Preliminary results. Transpl Int 4: 200‐204, 1991.
 150.Pham TT, Nguyen TT, Pathak S, Regmi S, Nguyen HT, Tran TH, Yong CS, Kim JO, Park PH, Park MH, Bae YK, Choi JU, Byun Y, Ahn CH, Yook S, Jeong JH. Tissue adhesive FK506‐loaded polymeric nanoparticles for multi‐layered nano‐shielding of pancreatic islets to enhance xenograft survival in a diabetic mouse model. Biomaterials 154: 182‐196, 2018.
 151.Pham‐Hua D, Padgett LE, Xue B, Anderson B, Zeiger M, Barra JM, Bethea M, Hunter CS, Kozlovskaya V, Kharlampieva E, Tse HM. Islet encapsulation with polyphenol coatings decreases pro‐inflammatory chemokine synthesis and T cell trafficking. Biomaterials 128: 19‐32, 2017.
 152.Pileggi A, Molano RD, Ricordi C, Zahr E, Collins J, Valdes R, Inverardi L. Reversal of diabetes by pancreatic islet transplantation into a subcutaneous, neovascularized device. Transplantation 81: 1318‐1324, 2006.
 153.Poulsen JS, Smith M, Deckert M, Deckert T. Comparison of intraperitoneal, intraportal and intravenous insulin infusion. Acta Endocrinol 95: 500‐504, 1980.
 154.Prochorov AV, Tretjak SI, Goranov VA, Glinnik AA, Goltsev MV. Treatment of insulin dependent diabetes mellitus with intravascular transplantation of pancreatic islet cells without immunosuppressive therapy. Adv Med Sci 53: 240‐244, 2008.
 155.Pullen LC. Stem cell‐derived pancreatic progenitor cells have now been transplanted into patients: Report from IPITA 2018. Am J Transplant 18: 1581‐1582, 2018.
 156.Qi M, Lacik I, Kollarikova G, Strand BL, Formo K, Wang Y, Marchese E, Mendoza‐Elias JE, Kinzer KP, Gatti F, Paushter D, Patel S, Oberholzer J. A recommended laparoscopic procedure for implantation of microcapsules in the peritoneal cavity of non‐human primates. J Surg Res 168: e117‐e123, 2011.
 157.Qi M, Morch Y, Lacik I, Formo K, Marchese E, Wang Y, Danielson KK, Kinzer K, Wang S, Barbaro B, Kollarikova G, Chorvat D Jr, Hunkeler D, Skjak‐Braek G, Oberholzer J, Strand BL. Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca2+ and Ba2+. Xenotransplantation 19: 355‐364, 2012.
 158.Rafael E, Tibell A, Ryden M, Lundgren T, Savendahl L, Borgstrom B, Arnelo U, Isaksson B, Nilsson B, Korsgren O, Permert J. Intramuscular autotransplantation of pancreatic islets in a 7‐year‐old child: A 2‐year follow‐up. Am J Transplant 8: 458‐462, 2008.
 159.Rajab A, Buss J, Diakoff E, Hadley GA, Osei K, Ferguson RM. Comparison of the portal vein and kidney subcapsule as sites for primate islet autotransplantation. Cell Transplant 17: 1015‐1023, 2008.
 160.Ratner BD. The biocompatibility manifesto: Biocompatibility for the twenty‐first century. J Cardiovasc Transl Res 4: 523‐527, 2011.
 161.Ray K, Badugu R, Lakowicz JR. Polyelectrolyte layer‐by‐layer assembly to control the distance between fluorophores and plasmonic nanostructures. Chem Mater 19: 5902‐5909, 2007.
 162.Reemtsma K. Experimental islet cell grafting: A transplantation model. Transplant Proc 2: 513‐515, 1970.
 163.Ricci M, Blasi P, Giovagnoli S, Rossi C, Macchiarulo G, Luca G, Basta G, Calafiore R. Ketoprofen controlled release from composite microcapsules for cell encapsulation: Effect on post‐transplant acute inflammation. J Control Release 107: 395‐407, 2005.
 164.Rickels MR, Mueller R, Markmann JF, Naji A. Effect of glucagon‐like peptide‐1 on beta‐ and alpha‐cell function in isolated islet and whole pancreas transplant recipients. J Clin Endocrinol Metab 94: 181‐189, 2009.
 165.Risbud MV, Bhargava S, Bhonde RR. 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, 2003.
 166.Roglic G, World Health Organization. Global Report on Diabetes. Geneva, Switzerland: World Health Organization, 2016, p. 86.
 167.Rokstad AM, Lacik I, de Vos P, Strand BL. Advances in biocompatibility and physico‐chemical characterization of microspheres for cell encapsulation. Adv Drug Deliv Rev 67‐68: 111‐130, 2014.
 168.Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM. Five‐year follow‐up after clinical islet transplantation. Diabetes 54: 2060‐2069, 2005.
 169.Sambathkumar R, Migliorini A, Nostro MC. Pluripotent stem cell‐derived pancreatic progenitors and beta‐like cells for type 1 diabetes treatment. Physiology (Bethesda) 33: 394‐402, 2018.
 170.Sarkar K, Xue Y, Sant S. Host response to synthetic versus natural biomaterials. In: Corradetti B, editor. The Immune Response to Implanted Materials and Devices: The Impact of the Immune System on the Success of an Implant. Cham: Springer International Publishing, 2017, p. 81‐105.
 171.Scarrit ME, Londono R, Badylak SF. Host Response to Implanted Materials and Devices: An Overview. In: Corradetti B, editor. The Immune Response to Implanted Materials and Devices. Switzerland: Springer International Publishing, 2017, p. 1‐14.
 172.Schaffellner S, Stadlbauer V, Stiegler P, Hauser O, Halwachs G, Lackner C, Iberer F, Tscheliessnigg KH. Porcine islet cells microencapsulated in sodium cellulose sulfate. Transplant Proc 37: 248‐252, 2005.
 173.Scharp DW, Lacy PE, Santiago JV, McCullough CS, Weide LG, Falqui L, Marchetti P, Gingerich RL, Jaffe AS, Cryer PE, Anderson CB, Flye MW. Insulin independence after islet transplantation into type I diabetic patient. Diabetes 39: 515‐518, 1990.
 174.Scharp DW, Marchetti P. Encapsulated islets for diabetes therapy: History, current progress, and critical issues requiring solution. Adv Drug Deliv Rev 67‐68: 35‐73, 2014.
 175.Scharp DW, Swanson CJ, Olack BJ, Latta PP, Hegre OD, Doherty EJ, Gentile FT, Flavin KS, Ansara MF, Lacy PE. Protection of encapsulated human islets implanted without immunosuppression in patients with type I or type II diabetes and in nondiabetic control subjects. Diabetes 43: 1167‐1170, 1994.
 176.Schweicher J, Nyitray C, Desai TA. Membranes to achieve immunoprotection of transplanted islets. Front Biosci (Landmark Ed) 19: 49‐76, 2014.
 177.Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo‐Jack S, Fish L, Heller SR, Rodriguez H, Rosenzweig J, Vigersky R. Hypoglycemia and diabetes: A report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 36: 1384‐1395, 2013.
 178.Sefton MV, May MH, Lahooti S, Babensee JE. Making microencapsulation work: Conformal coating, immobilization gels and in vivo performance. J Control Release 65: 173‐186, 2000.
 179.Shapiro AM. Islet transplantation in type 1 diabetes: Ongoing challenges, refined procedures, and long‐term outcome. Rev Diabet Stud 9: 385‐406, 2012.
 180.Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid‐free immunosuppressive regimen. N Engl J Med 343: 230‐238, 2000.
 181.Shapiro AM, Pokrywczynska M, Ricordi C. Clinical pancreatic islet transplantation. Nat Rev Endocrinol 13: 268‐277, 2017.
 182.Shapiro AMJ , Toso C, Imes S, Koh A, Kin T, O'Gorman D, Malcolm A, Dinyari P, Owen R, Kneteman NM, Bigam DL, Calne RY, Senior PA, and Roep BO. Five‐year results of islet‐alone transplantation match pancreas‐alone transplantation with alemtuzumab, Tac/MMF, with strong suppression of auto and alloreacivity. In: 13th World Congress of International Pancreas and Islet Transplant Association (IPITA). Prague, Czech Republic: The Review of Diabetic Studies, 2011, p. 95.
 183.Smink AM, de Vos P. Therapeutic strategies for modulating the extracellular matrix to improve pancreatic islet function and survival after transplantation. Curr Diab Rep 18: 39, 2018.
 184.Smood B, Bottino R, Hara H, Cooper DKC. Is the renal subcapsular space the preferred site for clinical porcine islet xenotransplantation? Review article. Int J Surg 69: 100‐107, 2019.
 185.Solass W, Horvath P, Struller F, Konigsrainer I, Beckert S, Konigsrainer A, Weinreich FJ, Schenk M. Functional vascular anatomy of the peritoneum in health and disease. Pleura Peritoneum 1: 145‐158, 2016.
 186.Song S, Blaha C, Moses W, Park J, Wright N, Groszek J, Fissell W, Vartanian S, Posselt AM, Roy S. An intravascular bioartificial pancreas device (iBAP) with silicon nanopore membranes (SNM) for islet encapsulation under convective mass transport. Lab Chip 17: 1778‐1792, 2017.
 187.Song S, Faleo G, Yeung R, Kant R, Posselt AM, Desai TA, Tang Q, Roy S. Silicon nanopore membrane (SNM) for islet encapsulation and immunoisolation under convective transport. Sci Rep 6: 23679, 2016.
 188.Soon‐Shiong P, Heintz RE, Merideth N, Yao QX, Yao Z, Zheng T, Murphy M, Moloney MK, Schmehl M, Harris M, Mendez R, Sandford PA. Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet 343: 950‐951, 1994.
 189.Stagner JI, Seelan RS, Parthasarathy RN. Maintenance of aerobic metabolism increases immunoisolated islet survival. Islets 3: 89‐92, 2011.
 190.Stephens CH, Orr KS, Acton AJ, Tersey SA, Mirmira RG, Considine RV, Voytik‐Harbin SL. In situ type I oligomeric collagen macroencapsulation promotes islet longevity and function in vitro and in vivo. Am J Physiol Endocrinol Metab 315: E650‐E661, 2018.
 191.Storrs R, Dorian R, King SR, Lakey J, Rilo H. Preclinical development of the Islet Sheet. Ann N Y Acad Sci 944: 252‐266, 2001.
 192.Su J, Hu BH, Lowe WL Jr, Kaufman DB, Messersmith PB. Anti‐inflammatory peptide‐functionalized hydrogels for insulin‐secreting cell encapsulation. Biomaterials 31: 308‐314, 2010.
 193.Sullivan SJ, Maki T, Borland KM, Mahoney MD, Solomon BA, Muller TE, Monaco AP, Chick WL. Biohybrid artificial pancreas: Long‐term implantation studies in diabetic, pancreatectomized dogs. Science 252: 718‐721, 1991.
 194.Sun AM, Parisius W, Healy GM, Vacek I, Macmorine HG. The use, in diabetic rats and monkeys, of artificial capillary units containing cultured islets of Langerhans (artificial endocrine pancreas). Diabetes 26: 1136‐1139, 1977.
 195.Sussman EM, Halpin MC, Muster J, Moon RT, Ratner BD. Porous implants modulate healing and induce shifts in local macrophage polarization in the foreign body reaction. Ann Biomed Eng 42: 1508‐1516, 2014.
 196.Tanenberg RJ, Newton CA, Drake AJ. Confirmation of hypoglycemia in the "dead‐in‐bed" syndrome, as captured by a retrospective continuous glucose monitoring system. Endocr Pract 16: 244‐248, 2010.
 197.Tateishi K, He J, Taranova O, Liang G, D'Alessio AC, Zhang Y. Generation of insulin‐secreting islet‐like clusters from human skin fibroblasts. J Biol Chem 283: 31601‐31607, 2008.
 198.Trivedi N, Steil GM, Colton CK, Bonner‐Weir S, Weir GC. Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor. Cell Transplant 9: 115‐124, 2000.
 199.Tuch BE, Keogh GW, Williams LJ, Wu W, Foster JL, Vaithilingam V, Philips R. Safety and viability of microencapsulated human islets transplanted into diabetic humans. Diabetes Care 32: 1887‐1889, 2009.
 200.Tze WJ, Wong FC, Chen LM, O'Young S. Implantable artificial endocrine pancreas unit used to restore normoglycaemia in the diabetic rat. Nature 264: 466‐467, 1976.
 201.Vaithilingam V, Bal S, Tuch BE. Encapsulated islet transplantation: Where do we stand? Rev Diabet Stud 14: 51‐78, 2017.
 202.Vaithilingam V, Evans MDM, Lewy DM, Bean PA, Bal S, Tuch BE. Co‐encapsulation and co‐transplantation of mesenchymal stem cells reduces pericapsular fibrosis and improves encapsulated islet survival and function when allografted. Sci Rep 7: 10059, 2017.
 203.Valdes‐Gonzalez R, Rodriguez‐Ventura AL, White DJ, Bracho‐Blanchet E, Castillo A, Ramirez‐Gonzalez B, Lopez‐Santos MG, Leon‐Mancilla BH, Dorantes LM. Long‐term follow‐up of patients with type 1 diabetes transplanted with neonatal pig islets. Clin Exp Immunol 162: 537‐542, 2010.
 204.Valdes‐Gonzalez RA, Dorantes LM, Garibay GN, Bracho‐Blanchet E, Mendez AJ, Davila‐Perez R, Elliott RB, Teran L, White DJ. Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: A 4‐year study. Eur J Endocrinol 153: 419‐427, 2005.
 205.Valdes‐Gonzalez RA, White DJ, Dorantes LM, Teran L, Garibay‐Nieto GN, Bracho‐Blanchet E, Davila‐Perez R, Evia‐Viscarra L, Ormsby CE, Ayala‐Sumuano JT, Silva‐Torres ML, Ramirez‐Gonzalez B. Three‐yr follow‐up of a type 1 diabetes mellitus patient with an islet xenotransplant. Clin Transplant 21: 352‐357, 2007.
 206.van Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes: Etiology, immunology, and therapeutic strategies. Physiol Rev 91: 79‐118, 2011.
 207.Vegas AJ, Veiseh O, Doloff JC, Ma M, Tam HH, Bratlie K, Li J, Bader AR, Langan E, Olejnik K, Fenton P, Kang JW, Hollister‐Locke J, Bochenek MA, Chiu A, Siebert S, Tang K, Jhunjhunwala S, Aresta‐Dasilva S, Dholakia N, Thakrar R, Vietti T, Chen M, Cohen J, Siniakowicz K, Qi M, McGarrigle J, Graham AC, Lyle S, Harlan DM, Greiner DL, Oberholzer J, Weir GC, Langer R, Anderson DG. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat Biotechnol 34: 345‐352, 2016.
 208.Vegas AJ, Veiseh O, Gurtler M, Millman JR, Pagliuca FW, Bader AR, Doloff JC, Li J, Chen M, Olejnik K, Tam HH, Jhunjhunwala S, Langan E, Aresta‐Dasilva S, Gandham S, McGarrigle JJ, Bochenek MA, Hollister‐Lock J, Oberholzer J, Greiner DL, Weir GC, Melton DA, Langer R, Anderson DG. Long‐term glycemic control using polymer‐encapsulated human stem cell‐derived beta cells in immune‐competent mice. Nat Med 22: 306‐311, 2016.
 209.Veiseh O, Doloff JC, Ma M, Vegas AJ, Tam HH, Bader AR, Li J, Langan E, Wyckoff J, Loo WS, Jhunjhunwala S, Chiu A, Siebert S, Tang K, Hollister‐Lock J, Aresta‐Dasilva S, Bochenek M, Mendoza‐Elias J, Wang Y, Qi M, Lavin DM, Chen M, Dholakia N, Thakrar R, Lacik I, Weir GC, Oberholzer J, Greiner DL, Langer R, Anderson DG. Size‐ and shape‐dependent foreign body immune response to materials implanted in rodents and non‐human primates. Nat Mater 14: 643‐651, 2015.
 210.Vethakkan SR, Walters JM, Gooley JL, Boston RC, Kay TW, Goodman DJ, Jenkins AJ, Ward GM. The incretin response after successful islet transplantation. Transplantation 97: e9‐e11, 2014.
 211.ViaCyte I . PEC‐Encap™ (VC‐01™). https://viacyte.com/products/pec‐encap‐vc‐01 (August 28, 2019), 2019.
 212.Wang T. Successful diabetes management without immunosuppressivedrugs in NHP model has been demonstrated. Encapsulation system with taperednanopore conduits achieved normal glycaemia with regulated insulin release. Artif Cells Nanomed Biotechnol 46: S1162‐S1168, 2018.
 213.Ward C, Faleo G, Duh Q, Hebrok M, Chang W, Stock P, Tang Q. Reversal of diabetes and preservation of pancreatic islet grafts in the extrahepatic space with novel parathyroid gland co‐transplantation. Transplantation 102: S368‐S369, 2018.
 214.Weaver JD, Headen DM, Aquart J, Johnson CT, Shea LD, Shirwan H, Garcia AJ. Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites. Sci Adv 3: e1700184, 2017.
 215.Weaver JD, Headen DM, Hunckler MD, Coronel MM, Stabler CL, Garcia AJ. Design of a vascularized synthetic poly(ethylene glycol) macroencapsulation device for islet transplantation. Biomaterials 172: 54‐65, 2018.
 216.Weber CJ, Hardy MA, Pi‐Sunyer F, Zimmerman E, Reemtsma K. Tissue culture preservation and intramuscular transplantation of pancreatic islets. Surgery 84: 166‐174, 1978.
 217.Wiles K, Fishman JM, De Coppi P, Birchall MA. The host immune response to tissue‐engineered organs: Current problems and future directions. Tissue Eng Part B Rev 22: 208‐219, 2016.
 218.Wolf MT, Dearth CL, Ranallo CA, LoPresti ST, Carey LE, Daly KA, Brown BN, Badylak SF. Macrophage polarization in response to ECM coated polypropylene mesh. Biomaterials 35: 6838‐6849, 2014.
 219.Wu ZG, Shi ZQ, Lu ZN, Yang H, Shi FY, Zheng XR, Sun AM. In vitro culture and transplantation of encapsulated human fetal islets as an artificial endocrine pancreas. ASAIO Trans 35: 736‐738, 1989.
 220.Yamada K, Hirakata A, Tchipashvili V, Shimizu A, Iwaki H, Griesemer A, Vallabhajosyula P, Moran S, Sachs DH. Composite islet‐kidneys from single baboon donors cure diabetes across fully allogenic barriers. Am J Transplant 11: 2603‐2612, 2011.
 221.Zhu H, Li W, Liu Z, Li W, Chen N, Lu L, Zhang W, Wang Z, Wang B, Pan K, Zhang X, Chen G. Selection of implantation sites for transplantation of encapsulated pancreatic islets. Tissue Eng Part B Rev 24: 191‐214, 2018.

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Braulio A. Marfil‐Garza, Kateryna Polishevska, Andrew R. Pepper, Gregory S. Korbutt. Current State and Evidence of Cellular Encapsulation Strategies in Type 1 Diabetes. Compr Physiol 2020, 10: 839-878. doi: 10.1002/cphy.c190033