Heterogeneous toroidal spiral particles for islet encapsulation

Abstract

Transplantable cell encapsulation systems present a promising approach to deliver a therapeutic solution from hormone-producing cells for the treatment of endocrine diseases like type 1 diabetes. However, the development of a broadly effective and safe transplantation system has been challenging. While some current micro-sized capsules have been optimized for adequate nutrient and metabolic transport, they lack the robustness and retrievability for the clinical safety translation that macro-devices may offer. An existing challenge to be addressed in the current macro-devices is their configuration which may lead to unsatisfactory mass transfer. Here, we design and characterize a millimeter-size particle system of poly-ethylene glycol (PEG) featuring internal toroidal spiral channels, called toroidal spiral particles (TSPs). The characteristic internal structure of the TSPs allows for large encapsulation capacity and large surface area available to all the encapsulated cell mass for effective molecular diffusion. The polymeric matrix renders the particle flexible yet robust for safe transplantation and retrieval. We demonstrate the feasibility of fabricating these particles with various polymer compositions, while optimizing their mechanical properties as well as glucose and insulin permeability. Encapsulation of islets of Langerhans is achieved with high loading capacity (∼160 IEQ per TSP) and excellent cell viability. TSP-encapsulated islets showed similar glucose-stimulated insulin secretion to the naked islets. Preliminary biocompatibility of the TSPs on naïve C57BL/6 mice shows minimal inflammatory response after 4-week transplantation into the intraperitoneal (IP) space. Long-term therapeutic efficacy of encapsulated islets needs to be confirmed in diabetic rodent models in the future, while determining minimal mass required to reverse diabetes. However, we believe from the in vitro favorable results and the TSPs’ unique design that TSPs may provide a safe, effective method to transplant and retrieve therapeutic cells for type 1 diabetes treatment and may also be applicable for other cell therapies.