Pore size of gelatin/hyaluronic acid supramolecular hydrogel modulates the immune functions of bone marrow-derived immature dendritic cells

The extracellular matrix-mimetic performance of hydrogel micropores makes them promising delivery carriers for dendritic cell (DC) vaccines. Nevertheless, the reported hydrogel failed to decouple the intricate relationship between pore size and mechanical performance, thus the regulatory effect of pore size on DCs immune function remains inadequately understood. In this study, we constructed a supramolecular hydrogel system in which pore size was decoupled from mechanical performance using a sacrificial gelatin microgel template and synergetic photopolymerization. The effects of hydrogel pore size on the immune function of immature bone marrow-derived dendritic cells (BMDCs) were investigated. Results showed that hydrogels with 15-μm pore-size significantly promoted BMDC migration and release; upregulated the expression of costimulatory molecules CD80, CD86, CD40 and major histocompatibility complex class II molecules; promoted the secretion of proinflammatory cytokines; and inhibited the expression of anti-inflammatory cytokines. In addition, BMDCs regulated by the 15-μm pore-size hydrogel promoted the differentiation of CD8+ effector T cells and inhibited the differentiation of CD8+ exhausted T cells and regulatory T cells. Thus, in supramolecular hydrogels, pore size acts as a biophysical cue for the immunomodulation of BMDCs. Our findings provide an experimental basis for improving the antitumor effect of DC vaccines.