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. This research presents a novel way to transport healing cells to the skin using a tool known as a cryomicroneedle. The scientists created a sponge-like microneedle (tiny needle) that can carry cells by immersing it in a cell suspension (liquid containing cells). This technique enables easy storage and movement of the microneedles, and the cells can be added on-site for immediate application or kept for future use. They tested this technique with three cell types related to wound healing, vitiligo (a skin condition that causes loss of skin color) treatment, and cancer vaccination. The findings revealed that the cryomicroneedles could effectively transport the cells to the skin and trigger the intended healing effects. This innovative method could potentially enhance the efficiency and convenience of cell treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author. Cryomicroneedles (cryoMNs) permit the precise delivery of therapeutic cells into the skin, but are limited by the cold-chain transportation and storage. This article introduces an innovative solution to use a prefabricated porous microneedle scaffold that can be shipped at room temperature and allow on-site cell loading and usage in the clinic (i.e., the second generation cryoMNs or S-cryoMNs). The study investigates 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.