Synthetic poly(ethylene glycol)-based microfluidic islet encapsulation reduces graft volume for delivery to highly vascularized and retrievable transplant site

Jessica D. Weaver, Devon M. Headen, Maria M. Coronel, Michael D. Hunckler, Haval Shirwan, Andrés J. García

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Transplant of hydrogel-encapsulated allogeneic islets has been explored to reduce or eliminate the need for chronic systemic immunosuppression by creating a physical barrier that prevents direct antigen presentation. Although successful in rodents, translation of alginate microencapsulation to large animals and humans has been hindered by large capsule sizes (≥500 μm diameter) that result in suboptimal nutrient diffusion in the intraperitoneal space. We developed a microfluidic encapsulation system that generates synthetic poly(ethylene glycol)-based microgels with smaller diameters (310 ± 14 μm) that improve encapsulated islet insulin responsiveness over alginate capsules and allow transplant within vascularized tissue spaces, thereby reducing islet mass requirements and graft volumes. By delivering poly(ethylene glycol)-encapsulated islets to an isolated, retrievable, and highly vascularized site via a vasculogenic delivery vehicle, we demonstrate that a single pancreatic donor syngeneic islet mass exhibits improved long-term function over conventional alginate capsules and close integration with transplant site vasculature. In vivo tracking of bioluminescent allogeneic encapsulated islets in an autoimmune type 1 diabetes murine model showed enhanced cell survival over unencapsulated islets in the absence of chronic systemic immunosuppression. This method demonstrates a translatable alternative to intraperitoneal encapsulated islet transplant.

Original languageEnglish (US)
Pages (from-to)1315-1327
Number of pages13
JournalAmerican Journal of Transplantation
Volume19
Issue number5
DOIs
StatePublished - May 2019
Externally publishedYes

Fingerprint

Microfluidics
Ethylene Glycol
Transplants
Capsules
Type 1 Diabetes Mellitus
Immunosuppression
Drug Compounding
Architectural Accessibility
Hydrogel
Antigen Presentation
Rodentia
Cell Survival
Insulin
Food
alginic acid

Keywords

  • antigen presentation/recognition
  • autoimmunity
  • basic (laboratory) research/science
  • bioengineering
  • diabetes: type 1
  • graft survival
  • islet transplantation
  • regenerative medicine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Synthetic poly(ethylene glycol)-based microfluidic islet encapsulation reduces graft volume for delivery to highly vascularized and retrievable transplant site. / Weaver, Jessica D.; Headen, Devon M.; Coronel, Maria M.; Hunckler, Michael D.; Shirwan, Haval; García, Andrés J.

In: American Journal of Transplantation, Vol. 19, No. 5, 05.2019, p. 1315-1327.

Research output: Contribution to journalArticle

Weaver, Jessica D. ; Headen, Devon M. ; Coronel, Maria M. ; Hunckler, Michael D. ; Shirwan, Haval ; García, Andrés J. / Synthetic poly(ethylene glycol)-based microfluidic islet encapsulation reduces graft volume for delivery to highly vascularized and retrievable transplant site. In: American Journal of Transplantation. 2019 ; Vol. 19, No. 5. pp. 1315-1327.
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