Prevascularized Retrievable Hybrid Implant to Enhance Function of Subcutaneous Encapsulated Islets

Auvro R. Mridha, Tim R. Dargaville, Paul D. Dalton, Luke Carroll, Michael B. Morris, Vijayaganapathy Vaithilingam, Bernard E. Tuch*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Web of Science)

Abstract

Replacement of pancreatic beta-cells is one of the most promising treatment options for treatment of type 1 diabetes (T1D), even though, toxic immunosuppressive drugs are required. In this study, we aim to deliver allogeneic beta-cell therapies without antirejection drugs using a bioengineered hybrid device that contains microencapsulated beta-cells inside 3D polycaprolactone (PCL) scaffolds printed using melt electrospin writing (MEW). Mouse beta-cell (MIN6) pseudoislets and QS mouse islets are encapsulated in alginate microcapsules, without affecting viability and insulin secretion. Microencapsulated MIN6 cells are then seeded within 3D MEW scaffolds, and these hybrid devices implanted subcutaneously in streptozotocin-treated diabetic NOD/SCID and BALB/c mice. Similar to NOD/SCID mice, blood glucose levels (BGL) are lowered from 30.1 to 4.8 mM in 25-41 days in BALB/c. In contrast, microencapsulated islets placed in prevascularized MEW scaffold 3 weeks after implantation in BALB/c mice normalize BGL (

Impact statement

The retrievable 3D printed PCL scaffold we have produced promotes vascularization when implanted subcutaneously and allows seeded microencapsulated insulin-producing cells to normalize blood glucose of diabetic mice for at least 2 months, without the need for antirejection drugs to be administered. The scaffold is scalable for possible human use, but will require modification to ensure that normalization of blood glucose levels can be maintained long term.

Original languageEnglish
Pages (from-to)212-224
Number of pages13
JournalTissue Engineering
Volume28
Issue number5-6
Early online date28 Nov 2020
DOIs
Publication statusPublished - 1 Mar 2022

Keywords

  • type 1 diabetes
  • cell therapy
  • islet transplantation
  • microencapsulation
  • melt electrowriting
  • vascularization
  • foreign body reaction
  • TRANSPLANTED ISLETS
  • BETA-CELLS
  • SCAFFOLDS
  • POLYMER
  • SITE
  • MICROCAPSULES
  • EFFICACY
  • DESIGN

Cite this