title: Mold-casted non-degradable, islet macro-encapsulating hydrogel devices for restoration of normoglycemia in diabetic mice.
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.
authors.affiliation: Simpson Querrey Institute for BioNanotechnology in Medicine, Northwestern University, 303 East Superior Street, Chicago, Illinois, 60611.|Department of Biomedical Engineering, Northwestern University, Evanston, Illinois.
authors.forename: Peter Daniel
authors.initials: PD
authors.lastname: Rios
authors.affiliation: Division of Transplantation, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Xunrong
authors.initials: X
authors.lastname: Luo
authors.affiliation: Simpson Querrey Institute for BioNanotechnology in Medicine, Northwestern University, 303 East Superior Street, Chicago, Illinois, 60611. ldshea@umich.edu.|Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd, Evanston, Illinois, 60208. ldshea@umich.edu.|Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, Illinois, 60208. ldshea@umich.edu.|The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 303 East Superior Street, Chicago, Illinois, 60611. ldshea@umich.edu.|Department of Obstetrics and Gynecology, Northwestern University, 205 East Superior Street, Chicago, Illinois, 60611. ldshea@umich.edu.|Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, Michigan, 48109-2099. ldshea@umich.edu.
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002214:Capsules / Q000138:chemical synthesis*; D002470:Cell Survival; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000473:pathology* / Q000628:therapy*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D020100:Hydrogels / Q000737:chemistry*; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000295:instrumentation*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016896:Treatment Outcome
chemical_list: D002214:Capsules; D020100:Hydrogels
keywords: encapsulation; hydrogel; macroencapsulation device; microchannels; polydimethylsiloxane (PDMS); polyethylene glycol (PEG)