Multifunctional hydrogel-based scaffold for improving the functionality of encapsulated therapeutic cells and reducing inflammatory response

Since the introduction of cell immunoisolation as an alternative to protect transplanted cells from host immune attack, much effort has been made to develop this technology into a realistic clinical proposal. Several promising approaches have been investigated to resolve the biotechnological and biosafety challenges related to cell microencapsulation. Here, a multifunctional hydrogel-based scaffold consisting of cell-loaded alginate-poly-l-lysine-alginate (APA) microcapsules and dexamethasone (DXM)-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres embedded in alginate hydrogel is developed and evaluated. Initially, the feasibility of using an alginate hydrogel for enclosing APA microcapsules was studied in a xenogeneic approach. In addition, the performance of the local release of DXM was addressed. The in vitro studies confirmed the correct adaptation of the enclosed cells to the scaffolds in terms of metabolic activity and viability. The posterior implantation of the hydrogel-based scaffolds containing cell-loaded microcapsules revealed that the hematocrit levels were maintained high and constant, and the pericapsular overgrowth was reduced in the DXM-treated rats for at least 2 months. This multifunctional scaffold might have a synergistic effect: (1) providing a physical support for APA microcapsules, facilitating administration, ensuring retention and recuperation and preventing dissemination; and (2) reducing post-transplantation inflammation and foreign body reaction, thus prolonging the lifetime of the implant by the continuous and localized release of DXM.