3D printed polyamide macroencapsulation devices combined with alginate hydrogels for insulin-producing cell-based therapies

Abstract

Cell macroencapsulation has shown a great potential overcoming the low survival of the transplanted pancreatic islets in the Type 1 Diabetes Mellitus (T1DM) treatment, as it avoids the need for lifelong immunosuppression. It is still not completely known how these devices interact with the host immune system when implanted. However, their surface properties seem to be crucial factors for a successful implant. In this context, the hydrophilicity and porosity of the surface of the macrocapsules are two of the most important properties that can affect the functionality of the graft; hydrophilicity defines the interactions with the host's immune cells, while the porosity determines the biosafety of the device while conditioning the oxygen, nutrients and insulin diffusion. Here, we report a novel β-cell macroencapsulation system that combines an injectable alginate hydrogel with an external 3D-printed implantable device. This external macrocapsule protects the inner hydrogel containing cells, while allowing the precise location of the implant in the body. In addition, it would allow the easy extraction of the grafted cells in the case the implant fails or the renewal of the therapeutic cells is required. This study evaluates the biological effect of the macroencapsulation devices' surface properties (hydrophilicity and porosity). We studied two different pore sizes and hydrophilicities in four different devices containing rat INS1E β-cells embedded in alginate hydrogels. All the devices showed great biocompatibility, although the hydrophilic ones exhibited higher fibroblast adhesion, which could potentially enhance the fibrotic response when implanted. Importantly, INS1E cells did not escape from the devices, denoting high biosafety. Cells grown within all devices and maintained their insulin secretory function. However, the hydrophobic device with a smaller pore size showed better cell viability values and, therefore, it might be the best candidate for the development of a safe β-cell replacement therapy in T1DM.

Keywords: Alginate; Hydrogel; Macroencapsulation; Type 1 Diabetes Mellitus.