**5.3 Immuno-modulation of alginate hydrogels**

To overcome the challenges of inflammation and fibrosis associated with the foreign body response after alginate hydrogels are implanted, researchers are currently trying to establish technologies for potential immune modulation. Research into alginate immune-modulation methods currently involves the use of bioactive nanoparticles, immune regulatory cells, hydrogel surface topography, and passive non-fouling agents [110]. In the past bioactive nanoparticles, like ketoprofen, have shown potential to modulate the degree of inflammation during FBR [111]. A recent study was able to load monoclonal antibody IgM nanoparticles during alginate encapsulation of pancreatic islets. This resulted in localized controlled release of the monoclonal antibody after implantation which decreased the immune response against transplants [112]. An islet transplantation study using the anti-inflammatory nanoparticle rapamycin, demonstrated reduced fibrosis and sustained glycemic control improvement [113]. Mesenchymal-derived stem cells have been shown to have a wide range of regenerative effects on several tissue injury types because of their multipotent capacity [114]. Several recent studies have demonstrated immune modulation of alginate hydrogels through co-delivery of MSCs with cell-delivery systems. This can help reduces inflammation and can modulate T-cell toxicity while also boosting wound healing properties and blood vessel formation of the graft site [115–117]. A better understanding of the mechanism of FBR in the future will help improve immune modulation technologies for transplantations involving alginate hydrogels.
