Nanofluidic microsystem for sustained intraocular delivery of therapeutics.

Globally, 145.2 million people suffer from moderate to severe vision impairment or blindness due to preventable or treatable causes. However, patient adherence to topical or intravitreal treatment is a leading cause of poor outcomes. To address this issue, we designed an intraocularly implantable device called the nanofluidic Vitreal System for Therapeutic Administration (nViSTA) for continuous and controlled drug release based on a nanochannel membrane that obviates the need for pumps or actuation. In vitro release analysis demonstrated that our device achieves sustained release of bimatoprost (BIM) and dexamethasone (DEX) at concentrations within clinically relevant therapeutic window. In this proof of concept study, we constructed an anatomically similar in silico human eye model to simulate DEX release from our implant and gain insight into intraocular pharmacokinetics profile. Overall, our drug-agnostic intraocular implant represents a potentially viable platform for long-term treatment of various chronic ophthalmologic diseases, including diabetic macular edema and uveitis.

Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats.

Pancreatic islet transplantation efficacy for type 1 diabetes (T1D) management is limited by hypoxia-related graft attrition and need for systemic immunosuppression. To overcome these challenges, we developed the Neovascularized Implantable Cell Homing and Encapsulation (NICHE) device, which integrates direct vascularization for facile mass transfer and localized immunosuppressant delivery for islet rejection prophylaxis. Here, we investigated NICHE efficacy for allogeneic islet transplantation and long-term diabetes reversal in an immunocompetent, male rat model. We demonstrated that allogeneic islets transplanted within pre-vascularized NICHE were engrafted, revascularized, and functional, reverting diabetes in rats for over 150 days. Notably, we confirmed that localized immunosuppression prevented islet rejection without inducing toxicity or systemic immunosuppression. Moreover, for translatability efforts, we showed NICHE biocompatibility and feasibility of deployment as well as short-term allogeneic islet engraftment in an MHC-mismatched nonhuman primate model. In sum, the NICHE holds promise as a viable approach for safe and effective islet transplantation and long-term T1D management.