Reconstructing hair follicle pigmentary unit using organoids and bioprinting

Hair graying is a common feature of physiological aging and is typically evaluated by hair color, melanin content, or melanogenesis-related enzyme activity. However, growing evidence suggests that hair graying results from functional defects at multiple levels of the hair follicle pigmentary unit (HFPU). The HFPU comprises both the intrinsic melanocyte lineage and the extrinsic microenvironment that supports melanocyte function. Here, we review the application of emerging technologies, including organoids, biomaterials, bioprinting, and microphysiological systems, to HFPU reconstruction. Based on the biological functions directly demonstrated by different models, we define six ascending levels of evidence: pigment production, melanocyte differentiation, pigment transfer, progenitor cell maintenance, niche reconstruction, and durable or cycle-like regenerative capacity. Current three-dimensional models reproduce selected structural or cellular components of the HFPU, but remain limited in their ability to sustain melanocyte-lineage renewal, support coordinated pigment transfer, and restore pigmentary function after perturbation. Distinguishing transient hair darkening or short-term melanogenic activation from functional HFPU reconstruction gives a more rigorous evaluation of hair repigmentation models and the interventions tested using these models.