In situ Forming Cryomicroneedles for Intradermal Cell Delivery

Abstract

Abstract Cryomicroneedles (cryoMNs) offer a convenient and minimally invasive way for the precise intradermal delivery of therapeutic cells in treating local and systematic diseases. They are manufactured by shaping and freezing the cell-containing cryogenic media in the microneedle template, allowing the package of cells in advance and direct usage in clinics. However, the current cryoMNs require cold-chain transportation and storage, and don’t permit the loading of the autologous cells in situ. This article introduces an in situ forming cryoMNs or the second generation of cryoMNs (S-cryoMNs) that address these limitations. Specifically, S-cryoMNs are made through 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.