3D-printed degradable hair follicular hanging-drop scaffolds integrated with tissue-engineered skin promote hair follicle regeneration in vitro

Abstract

Currently, a substantial number of patients suffer from the distress of skin defects. Tissue-engineered skin represents a promising alternative therapeutic option for these patients. However, the currently available tissue-engineered skin products still exhibit significant limitations, including poor long-term viability and a lack of appendages. The advent of three-dimensional (3D) printing technology and organoid formation techniques provides a promising avenue for addressing these challenges. In this study, we constructed a scaffold using 3D printing with sodium alginate (NaAlg)/gelatin (GEL)/alginate lyase hydrogel, which has controllable pore size and degradation rate. This scaffold provides a favorable microenvironment for the colonization and functional maturation of hair follicular hanging drops within artificially organized skin. In vitro observations revealed the regeneration of hair follicles and the high expression of hair follicle-specific markers, LIM homeobox 2 (LHX2), and cytokeratin 17 (CK17). In addition, we studied the follicular polarization of the engineered skin compared to normal skin and attempted to identify possible underlying mechanisms. In conclusion, our findings present a novel strategy for establishing artificial skin with appendages.

Keywords

3D bioprinting / Alginate lyase / Hair follicle / Microenvironment / Skin appendage regeneration