Flow focusing microfluidic device for pancreatic islets conformal coating in a PEG-based hydrogel

Conventional therapies for Type 1 Diabetes (T1D) aim to maintain glucose homeostasis and prevent long-term complications by administering exogenous insulin. A more promising strategy is to treat T1D with cell therapies: for this kind of treatment, islet transplantation is minimally invasive and safer than whole pancreas transplantation. However, the need of an immunosuppressive therapy severely limits its applicability. Conformal coating (CC) allows the encapsulation of single pancreatic islets in a polymeric membrane that conforms to the shape and size of the islets, resulting in a thin and uniform coating. The membrane allows exchange of small molecules, providing an immunoprotective and cell-supportive microenvironment. The present work shows how a soft lithographic microfluidic device can be utilized to obtain CC islets in a polyethylene glycol (PEG)-based hydrogel by coaxial injection of coating material and cells in an immiscible external oil phase through a built-in nozzle. The device was designed and tested to maximize coating conformality on NIT1 insulinoma cell clusters. Live/dead staining and confocal microscopy and glucose-stimulated insulin secretion were performed to assess the viability and functionality of the obtained CC clusters. In vitro results demonstrated how to obtain fully polymerized conformal capsules, having a coating thickness that allows passive diffusion of molecules that are critical for cell clusters survival and function, including oxygen, nutrients, and insulin without compromising the vitality and functionality of the encapsulated clusters.