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

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.

Microfluidic on-chip production of microgels using combined geometries

“…4 b), the shelter phase created an observable shielding between the aqueous phase droplets and crosslinking phase. In previous studies in which a kind of shielding was utilized, the dispersed phase droplets formed only in one locus or using one geometry 11 , 13 , 14 , 31 . However, in the present study, there were two droplet generation loci.…”

“…Since crosslinker could not reach the macromere before flow instability occurred, monodisperse, spherical droplets were formed. After droplet formation, the crosslinker diffused into droplets and cross-linked the PEG-4MAL macromer into the hydrogel network 13 , 14 .…”

In Vivo Imaging of Pancreatic Islet Grafts in Diabetes Treatment

“…Thus, the use of BLI has been confined to the study of cells and tissues in small rodents. BLI has been used to monitor the effects of 3D stem cell spheroids ( 13 ), poly(ethylene glycol)-encapsulants ( 14 ), mesenchymal stem cell-enriched scaffolds ( 16 ) or heparin-releasing silk fibroin scaffolds ( 17 ) on islet survival in vivo in rodents. The overall tolerance of islets for labeling them with perfluoro-15-crown-5-ether (PCE) emulsions for 19 F MRI ( 10 ) or poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with PCE and indocyanine green dye for 19 F MRI and near-infrared (NIR) fluorescence imaging ( 15 ) has also been evaluated with BLI.…”

“…For in vivo imaging, islets or cells are typically labeled prior to transplantation with the exception of SPECT and PET radiolabeling. For BLI, islets or beta-like cells, such as INS-1E cells, can be transfected or transduced with luciferase gene commonly derived from firefly (10)(11)(12)(13)(14)(15)(16)(17). Baculovirus has been used to mediate radiolabeling by 125 I for SPECT imaging (18).…”

Preferences of Type 1 Diabetic Patients on Devices for Islet Transplantation

“…Such information is critical because it could guide the designs of next-generation implantable devices, as T1D patients are the ultimate users of these products. These devices could generally be classified into two categories, that is, macro-devices 11 – 20 and microdevices 9 , 21 – 27 . In most cases, macro-devices are few centimeter-sized made of biomaterials with channels or chambers that could hold islets within.…”