Biomimetic cascade-released hydrogel scaffolds from microfluidics for efficient T cell recruitment and expansion

Adoptive T-cell immunotherapy has shown powerful therapeutic effects in cancer treatment. Attempts to implement T cell therapy have tended to focus on providing T cells with specific targeting and sufficient activation to enhance their tumor killing ability. Although biomaterial-based scaffolds can provide necessary molecular cues for T cell activation, efficient stimulation necessitates more attention on the reconstruction of natural T cell activation processes. Here, we present a novel biomimetic scaffold with cascade-released capacity for T-cell recruitment and activation. Core-shell structured hydrogel scaffolds are fabricated by single-step microfluidic electrospray, and chemokines and stimulatory antibodies are compartmentalized in the shell and core, respectively. Benefiting from the heterogeneity in the microstructure and swelling degree of the core and shell hydrogels, chemokine peptides are robustly released to recruit tumor-reactive T cells, and stimulatory antibodies are continuously released to support T cell proliferation. Such biomimetic recruitment and activation processes contribute to the formation of T cell clusters, which enhances their proliferation and infiltration in tumor tissues. Owing to the high expression of cytotoxic receptor and chemokine receptor, the activated T cells exhibit potent antitumor activity in vitro and in vivo. These features demonstrate that the cascade-released hydrogel scaffolds are promising for the local recruitment and activation of tumor-reactive T cells.