In situ-formed cryomicroneedles for intradermal cell delivery

Abstract Cryomicroneedles (cryoMNs) offer a convenient and minimally invasive way to precisely deliver therapeutic cells intradermally for treating local and systemic diseases. cryoMNs are manufactured by shaping and freezing the cell-containing cryogenic media in a microneedle template, which allows cells to be packaged in advance for direct usage in the clinic. However, the current cryoMNs require cold-chain transportation and storage and do not permit the loading of autologous cells in situ. This article introduces the second generation of cryoMNs (S-cryoMNs) that address these limitations. Specifically, S-cryoMNs are made by dipping a porous MN scaffold in the cell suspension before cryopreservation. The porous scaffold can be transported at room temperature, and researchers can load any cells with the optimized cryogenic medium. As a proof-of-concept, we examined the loading and intradermal delivery of three cell types in clinically relevant in vitro and in vivo models, including mesenchymal stem cells for wound healing, melanocytes for vitiligo treatment, and antigen-pulsed dendritic cells for cancer vaccination.