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

Jessica D. Weaver, Devon M. Headen, Jahizreal Aquart, Christopher T. Johnson, Lonnie D. Shea, Haval Shirwan, Andrés J. García

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1700184
JournalScience Advances
Volume3
Issue number6
DOIs
StatePublished - Jun 2017
Externally publishedYes

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Hydrogel
Transplants
Survival
Islets of Langerhans Transplantation
Biocompatible Materials
Adipose Tissue
Tissue Donors
Pancreatectomy
Hydrogels
Mesentery
Autologous Transplantation
Graft Survival
Complementary Therapies
Type 1 Diabetes Mellitus
Islets of Langerhans
Hypoglycemic Agents
Innate Immunity
Insulin
Inflammation

ASJC Scopus subject areas

  • General

Cite this

Weaver, J. D., Headen, D. M., Aquart, J., Johnson, C. T., Shea, L. D., Shirwan, H., & García, A. J. (2017). Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites. Science Advances, 3(6), [e1700184]. https://doi.org/10.1126/sciadv.1700184

Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites. / Weaver, Jessica D.; Headen, Devon M.; Aquart, Jahizreal; Johnson, Christopher T.; Shea, Lonnie D.; Shirwan, Haval; García, Andrés J.

In: Science Advances, Vol. 3, No. 6, e1700184, 06.2017.

Research output: Contribution to journalArticle

Weaver, Jessica D. ; Headen, Devon M. ; Aquart, Jahizreal ; Johnson, Christopher T. ; Shea, Lonnie D. ; Shirwan, Haval ; García, Andrés J. / Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites. In: Science Advances. 2017 ; Vol. 3, No. 6.
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