Organoid‐Loaded Cryomicroneedles for Biomimic Hair Regeneration

Abstract

Organoids have attracted extensive attention in the field of hair follicle (HF) tissue engineering and regeneration. However, HF organoid implantation faces a number of difficulties, such as low viability ratios, invasive trauma, and complicated procedures. To overcome these issues, a convenient and minimally invasive delivery approach with high efficiency and cell viability is required. Here, HF organoid‐loaded methacrylated gelatin‐cryomicroneedles (GelMA‐cryoMNs) that are capable of efficient transdermal delivery and can maintain the viability of the embedded organoids are developed. The GelMA‐cryoMNs are fabricated by a stepwise cryogenic molding process using a balanced ratio of cryopreservation agents and GelMA hydrogel. They can be inserted easily into porcine skin and melted without leaving residue after delivering the organoids. In vitro and in vivo, organoids delivered by the cryoMNs retain cell viability, self‐assembly, and differentiation ability. In mice, HF organoid‐loaded GelMA‐cryoMNs are delivered to the superficial dermis, resulting in subsequent HF development and the formation of an array of biomimetic hair tufts that broke through the skin surface. A promising strategy is provided here for biomimetic hair neogeneration that benefits from minimal invasion, low cost, and simple fabrication. The GelMA‐cryoMNs developed here could also have broader applications in tissue engineering and organ regeneration.

Advances and applications of biomimetic biomaterials for endogenous skin regeneration

“…In vitro 3D printing can precisely introduce complex adnexal structures within biomaterial tissue engineering matrix, and arrange cells into a biomimetic micropattern that simulated the tissue structures of dermis and hair follicles [ 100 ]. Zheng et al developed an HF organoid-loaded methacrylated gelatin-cryomicroneedles which could easily delivery the HF organoids under the skin [ 101 ]. Bio-3D printing and microneedle technologies have the advantages of high structural accuracy and precise customization of microstructures, and proving a promising strategy for HF regeneration.…”