Regulation of the Stem Cell-Host Immune System Interplay Using Hydrogel Coencapsulation System with an Anti-Inflammatory Drug

The host immune system is known to influence mesenchymal stem cell (MSC)‐mediated bone tissue regeneration. However, the therapeutic capacity of hydrogel biomaterial to modulate the interplay between MSCs and T‐lymphocytes is unknown. Here it is shown that encapsulating hydrogel affects this interplay when used to encapsulate MSCs for implantation by hindering the penetration of pro‐inflammatory cells and/or cytokines, leading to improved viability of the encapsulated MSCs. This combats the effects of the host pro‐inflammatory T‐lymphocyte‐induced nuclear factor kappaB pathway, which can reduce MSC viability through the CASPASE‐3 and CASPASE‐8 associated proapoptotic cascade, resulting in the apoptosis of MSCs. To corroborate rescue of engrafted MSCs from the insult of the host immune system, the incorporation of the anti‐inflammatory drug indomethacin into the encapsulating alginate hydrogel further regulates the local microenvironment and prevents pro‐inflammatory cytokine‐induced apoptosis. These findings suggest that the encapsulating hydrogel can regulate the MSC‐host immune cell interplay and direct the fate of the implanted MSCs, leading to enhanced tissue regeneration. The encapsulating hydrogel biomaterials, especially in the early stages of implantation, can regulate the mesenchymal stem cell–host immune system interplay and modulate the fate of the encapsulated stem cells. A new strategy is reported for enhanced bone regeneration in mesenchymal stem cell‐mediated therapies based on an RGD‐coupled alginate hydrogel coencapsulation system containing an anti‐inflammatory drug.