**1. Introduction**

Electrospinning is a process in which a charged polymer jet is deposited on a grounded collector. Introduced in the early 1900s, the technology is now a well-established and an intensively investigated way of producing continuous fibers from a wide variety of polymer solutions, with diameters ranging from several microns down to several nanometers [1]. With a high surface area to volume ratio, tunable porosity and flexibility in surface modification, electrospun fibers have been successfully used in various applications including the fabrication of protective clothing, electronics, catalysis and pharmaceutics, as well as in the fields of filtration, environmental engineering and regenerative medicine. Typically, a syringe is used to load the polymer solution and a syringe pump controls the solution flow rate from a tip charged by a high-voltage power unit. The charged polymer jet takes a torturous path, elongating and drying as it is pulled towards a grounded collector. Many modifications to the electrospinning setup have been investigated over the last couple of

decades [2,3]. For instance, a co-axial electrospinning system was developed to fabricate core-shell fibrous structures, wherein the inclusion of a sacrificial core can be used to yield hollow fibers or the inclusion of multiple cores can be used to yield multi-core fibers [4,5]. An axillary cylindrical electrode has also been used to facilitate multiple spinneret electrospinning that dramatically increases the rate of fiber production [6]. Similarly, conductive patterned collector-based electrospinning has been used to generate fibrous materials with controlled architectures [7].

Despite innovations in jet facilitation and control over path and fiber collection, the most commonly fabricated electrospun forms are flat membranes produced using flat collector plates, and tubular structures produced using rod-like collectors. In the context of biomedical applications, flat membranes are widely used as substrates for culturing a variety of cells and engineering tissues, such as skin [8], whereas the tubular structures are used to engineer tissues such as blood vessels and neural conduits [9]. Beyond these two forms, there is demand and scope for novel products and devices such as encapsulation systems that expand the reach of electrospinning applications in regenerative medicine. For example, a common approach used to treat type 1 diabetes mellitus is to infuse pancreatic islets into the hepatic portal vein; however, this implantation site has proven to be sub-optimal. The development of devices that encapsulate cells within a protective environment would facilitate the choice of alternative sites. In the field of tissue engineering, current *in vitro* approaches are unable to replicate native cell niche environments and hence there is interest in the development of *in vivo* bio-incubators that better replicate the tissue environment. Similarly, in the field of allo- or xeno-cell and tissue transplantation, the side effects of using immune suppressants are undesirable and there is increasing demand to develop suitable immuno-isolating devices [10,11].

In this report, we describe the fabrication of a macro-scale encapsulation device, produced through manipulation of the collection of electrospun fibers. It was hypothesized that the introduction of a water-soluble pellet (sacrificial core), such as a custom-made sodium chloride pellet, as the collector would allow for post-electrospinning dissolution of this sacrificial core, making it possible to fabricate a hollow polymeric macro-scale encapsulation device. Fabrication of capsules with varying size, shape and thickness would be possible by modifying the size, shape and thickness of the sacrificial core. It was further hypothesized that a framework would be required to prevent the collapse of the electrospun device upon sacrificial core dissolution, and therefore, it was proposed that a 3D printed framework would be used to support the sacrificial core during preparation and electrospinning, and that this framework would remain in place to prevent collapse following core dissolution. Polyamide 6,6 (PA66) was selected as the polymer of choice. This is a non-degradable and biocompatible polymer that has been widely explored in biomedical applications. The electrospun capsules produced were evaluated through the use of scanning electron microscopy (SEM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and simultaneous thermo gravimetric/differential thermal analysis (TG/DTA). Finally, protein diffusion studies using model biomolecules (insulin, albumin and Ig G) were performed to study the free diffusion of essential proteins through the capsule walls, and cell encapsulation studies with model cell types (fibroblasts and lymphocytes) were performed to investigate whether the device could support the viability of encapsulated cells whilst restricting immune cell access from the surrounding space.
