Mold‐casted non‐degradable, islet macro‐encapsulating hydrogel devices for restoration of normoglycemia in diabetic mice
dc.contributor.author | Rios, Peter Daniel | |
dc.contributor.author | Zhang, Xiaomin | |
dc.contributor.author | Luo, Xunrong | |
dc.contributor.author | Shea, Lonnie D. | |
dc.date.accessioned | 2016-10-17T21:18:00Z | |
dc.date.available | 2018-01-08T19:47:52Z | en |
dc.date.issued | 2016-11 | |
dc.identifier.citation | Rios, Peter Daniel; Zhang, Xiaomin; Luo, Xunrong; Shea, Lonnie D. (2016). "Mold‐casted non‐degradable, islet macro‐encapsulating hydrogel devices for restoration of normoglycemia in diabetic mice." Biotechnology and Bioengineering 113(11): 2485-2495. | |
dc.identifier.issn | 0006-3592 | |
dc.identifier.issn | 1097-0290 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/134144 | |
dc.description.abstract | Islet transplantation is a potential cure for diabetic patients, however this procedure is not widely adopted due to the high rate of graft failure. Islet encapsulation within hydrogels is employed to provide a three‐dimensional microenvironment conducive to survival of transplanted islets to extend graft function. Herein, we present a novel macroencapsulation device, composed of PEG hydrogel, that combines encapsulation with lithography techniques to generate polydimethylsiloxane (PDMS) molds. PEG solutions are mixed with islets, which are then cast into PDMS molds for subsequent crosslinking. The molds can also be employed to provide complex architectures, such as microchannels that may allow vascular ingrowth through pre‐defined regions of the hydrogel. PDMS molds allowed for the formation of stable gels with encapsulation of islets, and in complex architectures. Hydrogel devices with a thickness of 600 μm containing 500 islets promoted normoglycemia within 12 days following transplantation into the epididymal fat pad, which was sustained over the two‐month period of study until removal of the device. The inclusion of microchannels, which had a similar minimum distance between islets and the hydrogel surface, similarly promoted normoglycemia. A glucose challenge test indicated hydrogel devices achieved normoglycemia 90 min post‐dextrose injections, similar to control mice with native pancreata. Histochemical staining revealed that transplanted islets, identified as insulin positive, were viable and isolated from host tissue at 8 weeks post‐transplantation, yet devices with microchannels had tissue and vascular ingrowth within the channels. Taken together, these results demonstrate a system for creating non‐degradable hydrogels with complex geometries for encapsulating islets capable of restoring normoglycemia, which may expand islet transplantation as a treatment option for diabetic patients. Biotechnol. Bioeng. 2016;113: 2485–2495. © 2016 Wiley Periodicals, Inc.Macroencapsulating PEG hydrogel devices were created without microchannels (A) or cast in PDMS molds with column‐like features (B) to create hydrogels with microchannels (C, D). Islets were successfully encapsulated in these hydrogel devices (E, F), remained viable post‐encapsulation, and transplanted into the fat pad to restore normoglycemia in diabetic mice. | |
dc.publisher | Wiley Periodicals, Inc. | |
dc.subject.other | polydimethylsiloxane (PDMS) | |
dc.subject.other | polyethylene glycol (PEG) | |
dc.subject.other | hydrogel | |
dc.subject.other | encapsulation | |
dc.subject.other | macroencapsulation device | |
dc.subject.other | microchannels | |
dc.title | Mold‐casted non‐degradable, islet macro‐encapsulating hydrogel devices for restoration of normoglycemia in diabetic mice | |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | |
dc.subject.hlbsecondlevel | Ecology and Evolutionary Biology | |
dc.subject.hlbsecondlevel | Mathematics | |
dc.subject.hlbsecondlevel | Natural Resources and Environment | |
dc.subject.hlbsecondlevel | Statistics and Numeric Data | |
dc.subject.hlbsecondlevel | Public Health | |
dc.subject.hlbsecondlevel | Biological Chemistry | |
dc.subject.hlbtoplevel | Social Sciences | |
dc.subject.hlbtoplevel | Health Sciences | |
dc.subject.hlbtoplevel | Science | |
dc.description.peerreviewed | Peer Reviewed | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/134144/1/bit26005_am.pdf | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/134144/2/bit26005.pdf | |
dc.identifier.doi | 10.1002/bit.26005 | |
dc.identifier.source | Biotechnology and Bioengineering | |
dc.identifier.citedreference | Scharp DW, Marchetti P. 2013. Encapsulated islets for diabetes therapy: History, current progress, and critical issues requiring solution. Adv Drug Deliv Rev 67–68: 35 – 73. http://www.ncbi.nlm.nih.gov/pubmed/23916992 | |
dc.identifier.citedreference | Song S, Faleo G, Yeung R, Kant R, Posselt AM, Desai TA, Tang Q, Roy S. 2016. Silicon nanopore membrane (SNM) for islet encapsulation and immunoisolation under convective transport. Sci Rep 6: 23679. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4806308&tool=pmcentrez&rendertype=abstract | |
dc.identifier.citedreference | Song S, Roy S. 2015. Progress and challenges in macroencapsulation approaches for type 1 diabetes (T1D) treatment: Cells, biomaterials, and devices. Biotechnol Bioeng 9999: 1 – 22. http://www.readcube.com/articles/10.1002%2Fbit.25895?r3_referer=wol&tracking_action=preview_click&show_checkout=1&purchase_referrer=onlinelibrary.wiley.com&purchase_site_license=LICENSE_DENIED | |
dc.identifier.citedreference | Su J, Hu B‐H, Lowe WL, Kaufman DB, Messersmith PB. 2010. Anti‐inflammatory peptide‐functionalized hydrogels for insulin‐secreting cell encapsulation. Biomaterials 31: 308 – 314. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2784009&tool=pmcentrez&rendertype=abstract | |
dc.identifier.citedreference | Vaithilingam V, Tuch BE. 2011. Islet transplantation and encapsulation: An update on recent developments. Rev Diabet Stud 8: 51 – 67. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3143677&tool=pmcentrez&rendertype=abstract | |
dc.identifier.citedreference | Weber LM, Anseth KS. 2008. Hydrogel encapsulation environments functionalized with extracellular matrix interactions increase islet insulin secretion. Matrix Biol 27: 667 – 673. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2631362&tool=pmcentrez&rendertype=abstract | |
dc.identifier.citedreference | Phelps EA, Headen DM, Taylor WR, Thulé PM, García AJ. 2013. Vasculogenic bio‐synthetic hydrogel for enhancement of pancreatic islet engraftment and function in type 1 diabetes. Biomaterials 34: 4602 – 4611. http://www.ncbi.nlm.nih.gov/pubmed/23541111 | |
dc.identifier.citedreference | Pinkse GGM, Bouwman WP, Jiawan‐lalai R, Terpstra OT, Bruijn JA, Heer EDe. 2006. Integrin signaling via RGD peptides and anti‐B1 Abs confers resistance to apoptosis in islets of Langerhans. Diabetes 55: 1 – 6. | |
dc.identifier.citedreference | Qi M. 2014. Transplantation of encapsulated pancreatic islets as a treatment for patients with type 1 Diabetes Mellitus. Adv Med 2014: 1 – 15. http://www.hindawi.com/journals/amed/2014/429710/ | |
dc.identifier.citedreference | Rengifo HR, Giraldo JA, Labrada I, Stabler CL. 2014. Long‐term survival of allograft murine islets coated via covalently stabilized polymers. Adv Healthc Mater 3: 1061 – 1070. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4107175&tool=pmcentrez&rendertype=abstract | |
dc.identifier.citedreference | Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JRT, Shapiro AMJ. 2005. Five‐year follow‐up after clinical islet transplantation. Diabetes 54: 2060 – 2069. http://www.ncbi.nlm.nih.gov/pubmed/15983207 | |
dc.identifier.citedreference | Safley SA, Cui H, Cauffiel S, Tucker‐Burden C, Weber CJ. 2008. Biocompatibility and immune acceptance of adult porcine islets transplanted intraperitoneally in diabetic NOD mice in calcium alginate poly‐L‐lysine microcapsules versus barium alginate microcapsules without poly‐L‐lysine. J Diabetes Sci Technol 2: 760 – 767. | |
dc.identifier.citedreference | Salvay DM, Rives CB, Zhang X, Chen F, Kaufman DB, Lowe WL, Shea LD. 2008. Extracellular matrix protein‐coated scaffolds promote the reversal of diabetes after extrahepatic islet transplantation. Transplantation 85: 1456 – 1464. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2597660&tool=pmcentrez&rendertype=abstract | |
dc.identifier.citedreference | Shikanov A, Smith RM, Xu M, Woodruff TK, Shea LD. 2011. Hydrogel network design using multifunctional macromers to coordinate tissue maturation in ovarian follicle culture. Biomaterials 32: 2524 – 2531. http://www.sciencedirect.com/science/article/pii/S0142961210015875 | |
dc.identifier.citedreference | Zustiak SP, Boukari H, Leach JB. 2010. Solute diffusion and interactions in cross‐linked poly(ethylene glycol) hydrogels studied by fluorescence correlation spectroscopy Soft Matter 6: 3609. http://xlink.rsc.org/?DOI=c0sm00111b | |
dc.identifier.citedreference | 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. | |
dc.identifier.citedreference | Wilson JT, Chaikof EL. 2009. Challenges in immunoisolation. Adv Drug Deliv Rev 60: 124 – 145. | |
dc.identifier.citedreference | Kumagai‐Braesch M, Jacobson S, Mori H, Jia X, Takahashi T, Wernerson A, Flodström‐Tullberg M, Tibell A. 2013. The theracyte TM device protects against islet allograft rejection in immunized hosts. Cell Transplant 22: 1137 – 1146. | |
dc.identifier.citedreference | Liao SW, Rawson J, Omori K, Ishiyama K, Mozhdehi D, Oancea AR, Ito T, Guan Z, Mullen Y. 2013. Maintaining functional islets through encapsulation in an injectable saccharide‐peptide hydrogel. Biomaterials 34: 3984 – 3991. http://www.ncbi.nlm.nih.gov/pubmed/23465491 | |
dc.identifier.citedreference | Lin C‐C, Metters AT, Anseth KS. 2009. Functional PEG‐peptide hydrogels to modulate local inflammation induced by the pro‐inflammatory cytokine TNFalpha. Biomaterials 30: 4907 – 4914. | |
dc.identifier.citedreference | Liu XY, Nothias J‐M, Scavone A, Garfinkel M, Millis JM. 2015. Biocompatibility investigation of polyethylene glycol and alginate‐poly‐L‐lysine for islet encapsulation. ASAIO J 56: 241 – 245. http://www.ncbi.nlm.nih.gov/pubmed/20400892 | |
dc.identifier.citedreference | Weber LM, Lopez CG, Anseth KS. 2009. Effects of PEG hydrogel crosslinking density on protein diffusion and encapsulated islet survival and function. J Biomed Mater Res A 90: 720 – 729. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2913724&tool=pmcentrez&rendertype=abstract | |
dc.identifier.citedreference | Weber LM, Hayda KN, Haskins K, Anseth KS. 2007. The effects of cell‐matrix interactions on encapsulated beta‐cell function within hydrogels functionalized with matrix‐derived adhesive peptides. Biomaterials 28: 3004 – 3011. http://www.ncbi.nlm.nih.gov/pubmed/17391752 | |
dc.identifier.citedreference | Beck J, Angus R, Madsen B, Britt D, Vernon B, Nguyen KT. 2007. Islet encapsulation: Strategies to enhance islet cell functions. Tissue Eng 13: 589 – 599. http://www.ncbi.nlm.nih.gov/pubmed/17518605 | |
dc.identifier.citedreference | Blomeier H, Zhang X, Rives C, Brissova M, Hughes E, Baker M, Powers AC, Kaufman DB, Shea LD, Lowe WL. 2006. Polymer scaffolds as synthetic microenvironments for extrahepatic islet transplantation. Transplantation 82: 452 – 459. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2648394&tool=pmcentrez&rendertype=abstract | |
dc.identifier.citedreference | Buder B, Alexander M, Krishnan R, Chapman DW, Lakey JR. 2013. Encapsulated islet transplantation: Strategies and clinical trials. Immune Netw 13: 235 – 239. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3875781&tool=pmcentrez&rendertype=abstract | |
dc.identifier.citedreference | Chiu Y‐C, Cheng M‐H, Engel H, Kao S‐W, Larson JC, Gupta S, Brey EM. 2011. The role of pore size on vascularization and tissue remodeling in PEG hydrogels. Biomaterials 32: 6045 – 6051. http://www.ncbi.nlm.nih.gov/pubmed/21663958 | |
dc.identifier.citedreference | Colton CK. 2014. Oxygen supply to encapsulated therapeutic cells. Adv Drug Deliv Rev 68: 93 – 110. | |
dc.identifier.citedreference | 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. 2013. Enhanced function of immuno‐isolated islets in diabetes therapy byco‐encapsulation with an anti‐inflammatory drug. Biomaterials 34: 5792 – 5801. http://dx.doi.org/10.1016/j.biomaterials.2013.04.016 | |
dc.identifier.citedreference | Desai TA, West T, Cohen M, Boiarski T, Rampersaud A. 2004. Nanoporous microsystems for islet cell replacement. Adv Drug Deliv Rev 56: 1661 – 1673. http://www.sciencedirect.com/science/article/pii/S0169409x04001462 | |
dc.identifier.citedreference | de Souza YEDM, Chaib E, de Lacerda De PG, Crescenzi A, Bernal‐Filho A, D’Albuquerque LAC. 2011. Islet transplantation in rodents. Do encapsulated islets really work ? Arq Gastroenterol 48: 146 – 152. | |
dc.identifier.citedreference | Gibly RF, Graham JG, Luo X, Lowe WL, Hering BJ, Shea LD. 2011. Advancing islet transplantation: From engraftment to the immune response. Diabetologia 54: 2494 – 2505. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3193607&tool=pmcentrez&rendertype=abstract | |
dc.identifier.citedreference | Gruessner RWG, Gruessner AC. 2013. The current state of pancreas transplantation. Nat Rev Endocrinol 9: 555 – 562. http://www.ncbi.nlm.nih.gov/pubmed/23897173 | |
dc.identifier.citedreference | Hudalla GA, Eng TS, Murphy WL. 2008. An approach to modulate degradation and mesenchymal stem cell behavior in poly(ethylene glycol) networks. Biomacromolecules 9: 842 – 849. http://dx.doi.org/10.1021/bm701179s | |
dc.identifier.citedreference | Jang JY, Lee DY, Park SJ, Byun Y. 2004. Immune reactions of lymphocytes and macrophages against PEG‐grafted pancreatic islets. Biomaterials 25: 3663 – 3669. http://www.ncbi.nlm.nih.gov/pubmed/15020141 | |
dc.identifier.citedreference | Jeong J‐H, Yook S, Hwang JW, Jung MJ, Moon HT, Lee DY, Byun Y. 2013. Synergistic effect of surface modification with poly(ethylene glycol) and immunosuppressants on repetitive pancreatic islet transplantation into antecedently sensitized rat. Transplant Proc 45: 585 – 590. http://www.sciencedirect.com/science/article/pii/S0041134512006768 | |
dc.identifier.citedreference | Kharkar PM, Kiick KL, Kloxin AM. 2015. Design of thiol‐ and light‐sensitive degradable hydrogels using michael‐type addition reactions. Polym Chem 6: 5565 – 5574. http://pubs.rsc.org/en/content/articlehtml/2015/py/c5py00750j | |
dc.identifier.citedreference | Kizilel S, Scavone A, Liu X, Nothias J‐M, Ostrega D, Witkowski P, Millis M. 2010. Encapsulation of pancreatic islets within nano‐thin functional polyethylene glycol coatings for enhanced insulin secretion. Tissue Eng Part A 16: 2217 – 2228. http://online.liebertpub.com/doi/abs/10.1089/ten.TEA.2009.0640?url_ver=Z39.88‐2003&rfr_id=ori%3Arid%3Acrossref.orgrfr_dat=cr_pub%3Dpubmed | |
dc.identifier.citedreference | Merani S, Toso C, Emamaullee J, Shapiro AMJ. 2008. Optimal implantation site for pancreatic islet transplantation. Br J Surg 95: 1449 – 1461. http://www.ncbi.nlm.nih.gov/pubmed/18991254 | |
dc.identifier.citedreference | O’Sullivan ES, Vegas A, Anderson DG, Weir GC. 2011. Islets transplanted in immunoisolation devices: A review of the progress and the challenges that remain. Endocr Rev 32: 827 – 844. http://www.ncbi.nlm.nih.gov/pubmed/21951347 | |
dc.identifier.citedreference | Papavasiliou G, Sokic S, Turturro M. 2012. Synthetic PEG hydrogels as extracellular matrix mimics for tissue engineering applications. In: Sammour R, editor. Biotechnology—Molecular studies and novel applications for improved quality of human life. ISBN: 978‐953‐51‐0151‐2, InTech, Available from: http://www.intechopen.com/books/biotechnology‐molecular‐studies‐and‐novel‐applications‐for‐improved‐quality‐of‐human‐life/synthetic‐peg‐hydrogels‐as‐extracellular‐matrix‐mimics‐for‐tissue‐engineering‐applicationsInTech | |
dc.identifier.citedreference | Park H‐S, Kim J‐W, Lee S‐H, Yang HK, Ham D‐S, Sun C‐L, Hong TH, Khang G, Park C‐G, Yoon K‐H. 2015. Antifibrotic effect of rapamycin containing polyethylene glycol‐coated alginate microcapsule in islet xenotransplantation. J Tissue Eng Regen Med 1 – 11. http://www.ncbi.nlm.nih.gov/pubmed/26043934 | |
dc.identifier.citedreference | Phelps EA, Enemchukwu NO, Fiore VF, Sy JC, Murthy N, Sulchek TA, Barker TH, García AJ. 2012. Maleimide cross‐linked bioactive PEG hydrogel exhibits improved reaction kinetics and cross‐linking for cell encapsulation and in situ delivery. Adv Mater 24: 64 – 70, 2. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3517145&tool=pmcentrez&rendertype=abstract | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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