3D bioprinting of calcium molybdate nanoparticles-containing immunomodulatory bioinks for hair regrowth

The regeneration of hair follicles in skin defect area remains a huge challenge all over the world. However, there is no effective strategy to solve this problem due to the difficulty of harvesting hair follicles in anagen period. Herein, we design a bioink based on calcium molybdate (CM) nanoparticles, laden with dermal papilla cells (DPCs) and macrophages. Interestingly, an anti-inflammatory microenvironment is established by the release of molybdenum (Mo) ions, thereby achieving favorable immunomodulation of bioactive ions-mediated hair regrowth. It is demonstrated that in the CM nanoparticles-containing multicellular bioinks, Mo polarizes macrophages into M2 phenotype to secret anti-inflammatory cytokines. Furthermore, it is shown that the anti-inflammatory immune microenvironment of the scaffolds induces the secretion of hair follicle anagen-related cytokines in DPCs, promoting hair regrowth in vivo. Finally, transcriptomic analysis reveals the underlying mechanism that Mo activates the mammalian target of rapamycin (mTOR) signaling pathway in macrophages and up-regulates the expression of growth factors (HGF and IGF-1), which accelerate the transition of hair follicles to anagen period. This study offers a new insight and strategy for the reconstruction of complex skin appendages through bioprinting immunomodulatory multicellular scaffolds with inorganic bioinks.