Hair Follicle Seedling Cryomicroneedles from Hierarchical Microfluidic Organoid on a Chip

Hair follicle organoids (HFOs) have demonstrated revolutionary regenerative potential in hair follicle regeneration, while their high-throughput production, uniform morphology, excellent hair growth potential, and simple and efficient intradermal transplantation are still challenges. In this paper, we present novel hair follicle seedling cryomicroneedles to achieve bionic hair regeneration by using a hierarchical microfluidic organoid-on-a-chip. Our integrated chip features a fluidic channel module and a hierarchical microneedle template module, enabling microflow-guided uniform cell distribution into needle-shaped microwells to form HFOs. Cryopreservation agents (CPA)-containing pregel solutions are injected to encapsulate HFOs following UV gelation, and the final HFO-loaded cryomicroneedle (cryoMN@HFO) is obtained after freezing and demolding. We have demonstrated that the cryoMNs@HFOs could preserve homogeneous HFO morphology, favorable viability, and excellent hair growth potential. Besides, the cryoMN@HFOs possess good skin penetration ability and biosafety, enabling rapid transplantation of HFOs into the dermis. Thus, after intradermal transplantation in animal experiments, the delivered organoids develop into fully functional hair follicles with mature structures in vivo. Based on these advantages, we believe that this technology holds promise for human hair follicle reconstruction.