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Sci Adv. 2017 Jun 2;3(6):e1700184. doi: 10.1126/sciadv.1700184. eCollection 2017 Jun.

Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites.

Author information

1
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
2
Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
3
Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Atlanta, GA, 30332, USA.
4
Department of Biomedical Engineering and Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
5
Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Suite 03-2303, 250 East Superior Street, Chicago, IL 60611, USA.
6
Institute of Cellular Therapeutics, Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
7
FasCure Therapeutics LLC, 300 East Market Street, Louisville, KY 40202, USA.

Abstract

Islet transplantation is a promising alternative therapy for insulin-dependent patients, with the potential to eliminate life-threatening hypoglycemic episodes and secondary complications of long-term diabetes. However, widespread application of this therapy has been limited by inadequate graft function and longevity, in part due to the loss of up to 60% of the graft in the hostile intrahepatic transplant site. We report a proteolytically degradable synthetic hydrogel, functionalized with vasculogenic factors for localized delivery, engineered to deliver islet grafts to extrahepatic transplant sites via in situ gelation under physiological conditions. Hydrogels induced differences in vascularization and innate immune responses among subcutaneous, small bowel mesentery, and epididymal fat pad transplant sites with improved vascularization and reduced inflammation at the epididymal fat pad site. This biomaterial-based strategy improved the survival, engraftment, and function of a single pancreatic donor islet mass graft compared to the current clinical intraportal delivery technique. This biomaterial strategy has the potential to improve clinical outcomes in islet autotransplantation after pancreatectomy and reduce the burden on donor organ availability by maximizing graft survival in clinical islet transplantation for type 1 diabetes patients.

KEYWORDS:

Inflammation; biomaterial; blood glucose; diabetes; hydrogel; in vivo imaging; islet; pancreas; transplantation; vascularization

PMID:
28630926
PMCID:
PMC5457148
DOI:
10.1126/sciadv.1700184
[Indexed for MEDLINE]
Free PMC Article

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