Methacrylated Gellan Gum/Poly-<scp>l</scp>-lysine Polyelectrolyte Complex Beads for Cell-Based Therapies

Cell encapsulation strategies using hydrogel beads have been considered as an alternative to immunosuppression in cell-based therapies. They rely on layer-by-layer (LbL) deposition of polymers to tune beads' permeability, creating a physical barrier to the host immune system. However, the LbL approach can also create diffusion barriers, hampering the flow of essential nutrients and therapeutic cell products. In this work, the polyelectrolyte complex (PEC) methodology was used to circumvent the drawbacks of the LbL strategy by inducing hydrogel bead formation through the interaction of anionic methacrylated gellan gum (GG-MA) with cationic poly-l-lysine (PLL). The interfacial complexation between both polymers resulted in beads with a cell-friendly GG-MA hydrogel core surrounded by a PEC semipermeable membrane. The beads showed great <i>in vitro</i> stability over time, a semi-permeable behavior, and supported human adipose-derived stem cell encapsulation. Additionally, and regarding immune recognition, the <i>in vitro</i> and <i>in vivo</i> studies pointed out that the hydrogel beads behave as an immunocompatible system. Overall, the engineered beads showed great potential for hydrogel-mediated cell therapies, when immunoprotection is required, as when treating different metabolic disorders.