Hydrogel injection molded islet macroencapsulation devices to treat diabetes in a non-human primate model

PROJECT SUMMARY/ABSTRACT
Type 1 diabetes (T1D) is a disease affecting approximately 1.7 million adults and children in the United States,
and typically results in life-long dependence on injected insulin for survival. Clinical islet transplantation is a
promising FDA approved alternative therapy for T1D, with the potential to reduce or eliminate secondary
complications. However, islet transplantation has limited widespread application due to short-term transplant
lifespans caused by poor graft vascularization, ineffective and toxic immunosuppressive drug regimens, and
immune rejection. Newer stem cell-derived insulin secreting cell technologies will almost certainly be necessary
to address patient accessibility concerns, but still pose significant potential safety concerns. Methods to eliminate
graft rejection in the absence of chronic systemic immunosuppression and devices to isolate the graft from the
patient and enable full graft retrieval will vastly expand the eligible patient population, reduce risks associated
with this therapy, and are critical to translation of cell therapy for the treatment of T1D. Macroencapsulation in
non-degradable hydrogel devices has been proposed as a means to address these limitations, but clinical
success has been limited due to challenges with manufacturing complex device geometries with high surface
area to volume (SA/V) ratios for adequate oxygen transport and long-term engraftment. To this end,
ImmunoShield Therapeutics has recently developed a hydrogel injection molding-based method to generate high
SA/V hydrogel macroencapsulation devices and has spent considerable time performing in silico, in vitro, and in
vivo experiments, including in our Phase I project, to optimize this technology for islet macroencapsulation, which
we have shown can reverse diabetes in preclinical small animal models. Hydrogel injection molding can generate
macroencapsulated cell therapy devices with complex geometries faster (≥ 50%) and cheaper than other leading
methods, with greater reliability and construct stability and integrity, and it is our expectation that
commercialization of this technology will enable facile translation of regenerative medicine products from the
laboratory to the clinic, including macroencapsulated islets or stem cell-derived insulin secreting cells. Therefore,
in this Phase II project, we will evaluate hydrogel injection molded macroencapsulation devices for islet
transplantation in non-human primate studies, with the goal of generating biocompatibility, toxicology, and CMC
data for future FDA submissions. This will be achieved through (1) evaluating tissue remodeling responses to
hydrogel injection molded macroencapsulation devices, (2) assessing macroencapsulated islet survival and host
immune and metabolic responses to devices, and (3) demonstrating macroencapsulated islet function in a
diabetic non-human primate model. Completion of this Phase II project will de-risk hydrogel injection molding
technology and macroencapsulated cell therapies for type 1 diabetes, which will in turn attract Phase III funding
to support commercialization efforts.

Grant Number: 2R44DK136496-02
NIH Institute/Center: NIH
Principal Investigator: Matthew Becker