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Regulatory T (T reg ) cells underlie multiple autoimmune disorders and potentialize an anti-inflammation treatment with adoptive cell therapy. However, systemic delivery of cellular therapeutics often lacks tissue targeting and accumulation for localized autoimmune diseases. Besides, the instability and plasticity of T reg cells also induce phenotype transition and functional loss, impeding clinical translation. Here, we developed a perforated microneedle (PMN) with favorable mechanical performance and a spacious encapsulation cavity to support cell survival, as well as tunable channels to facilitate cell migration for local T reg therapy of psoriasis. In addition, the enzyme-degradable microneedle matrix could release fatty acid in the hyperinflammatory area of psoriasis, enhancing the T reg suppressive functions via the fatty acid oxidation (FAO)-mediated metabolic intervention. T reg cells administered through PMN substantially ameliorated psoriasis syndrome with the assistance of fatty acid-mediated metabolic intervention in a psoriasis mouse model. This tailorable PMN could offer a transformative platform for local cell therapy to treat a variety of diseases.

The dynamic roles of T cells in the immune system to recognize and destroy the infected or mutated cells render T cell therapy a prospective treatment for a variety of diseases including cancer, autoimmune diseases, and allograft rejection. However, the clinical applications of T cell therapy remain unsatisfactory due to the tedious manufacturing process, off-target cytotoxicity, poor cell persistence, and associated adverse effects. To this end, various biomaterials have been introduced to enhance T cell therapy by facilitating proliferation, enhancing local enrichment, prolonging retention, and alleviating side effects. This review highlights the design strategies of biomaterials developed for T cell expansion, enrichment, and delivery as well as their corresponding therapeutic effects. The prospects of biomaterials for enhancing T cell immunotherapy are also discussed in this review. [Display omitted] [ABSTRACT FROM AUTHOR]