Abstract
Encapsulated beta cell transplantation offers a potential cure for a subset of diabetic patients. Once transplanted, beta cell grafts can help to restore glycemic control; however, locating and retrieving cells in the event of graft failure may pose a surgical challenge. Here, a dual-function nanoparticle-loaded hydrogel microcapsule is developed that enables graft retrieval under an applied magnetic field. Additionally, this system facilitates graft localization via magnetic resonance imaging (MRI), and graft isolation from the immune system. Iron oxide nanoparticles encapsulated within alginate hydrogel capsules containing viable islets are transplanted and the in vitro and in vivo retrieval of capsules containing nanoparticles functionalized with various ligands are compared. Capsules containing islets co-encapsulated with COOH-coated nanoparticles restore normal glycemia in immunocompetent diabetic mice for at least 6 weeks, can be visualized using MRI, and are retrievable in a magnetic field. Application of a magnetic field for 90 s via a magnetically assisted retrieval device facilitates rapid retrieval of up to 94% (±3.1%) of the transplant volume 24 h after surgical implantation. This strategy aids monitoring of cell-capsule locations in vivo, facilitates graft removal at the end of the transplant lifetime, and may be applicable to many encapsulated cell transplant systems.
Highlights
For patients with diabetes, islet transplantation can help to restore insulin secretion and longterm normoglycemia,[1, 2] offering a potential alternative to daily insulin injections
To develop hydrogel capsules which can be magnetically retrieved, we incorporated iron oxide nanoparticles coated with different functional groups into the hydrogel aqueous phase before droplet generation
Three iron oxide nanoparticle systems were tested; unfunctionalized nanoparticles (NP), nanoparticles functionalized with poly-ethylene glycol (NP-PEG), or nanoparticles functionalized with carboxylic acid groups (NP-COOH)
Summary
Islet transplantation can help to restore insulin secretion and longterm normoglycemia,[1, 2] offering a potential alternative to daily insulin injections. Cell and organoid grafts can be encapsulated within hydrogel materials prior to transplantation.[6,7,8,9] The hydrogels help to physically isolate the graft from the host immune system, reducing the need for systemic immunosuppression, and limit cellular rejection following transplantation.[10, 11] Recently, chemically modified hydrogels have been developed which can reduce foreign body responses and associated material fibrosis.[8, 12] This has enabled the transplant of cell and organoid therapies to a wider range of accessible extra-hepatic transplant sites in small animal models and nonhuman primates.[8, 9]
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