A three-dimensional bioprinting technique, based on a gelatin/alginate hydrogel, for the tissue engineering of hair follicle reconstruction

Int J Biol Macromol. 2021 Sep 9:S0141-8130(21)01927-9. doi: 10.1016/j.ijbiomac.2021.09.014. Online ahead of print.


Hair loss remains a challenging clinical problem that influences the quality of life. Three-dimensional (3D) bioprinting has become a valuable tool for fabricating tissue constructs for transplantation and other biomedical applications. Although some simple organs, such as skin and cartilage, have been successfully simulated, it remains challenging to make hair follicles (HFs), which are highly complex organs. The tissue engineering of human HFs has been a long-standing challenge, and progress with this has lagged behind that with other lab-grown tissues. This is principally due to a lack of availability of a platform that can successfully recapitulate the microenvironmental cues required to maintain the requisite cellular interactions for hair neogenesis. In this study, we used a 3D bioprinting technique based on a gelatin/alginate hydrogel to construct a multilayer composite scaffold with cuticular and corium layers to simulate the microenvironment of dermal papilla cells (DPCs) in the human body. This new approach permits the controllable formation of self-aggregating spheroids of DPCs in a physiologically relevant extracellular matrix and the initiation of epidermal-mesenchymal interactions, which results in HF formation in vivo. In conclusion, our 3D-bioprinted multilayer composite scaffold prepared using a gelatin/alginate hydrogel provides a suitable 3D microenvironment for DPCs to induce HF formation. The ability to regenerate entire HFs should have a significant impact on the medical management of hair loss. This method may also have critical applications for skin tissue engineering, with its appendages, for other purposes.

Keywords: 3D bioprinting; Dermal papilla cell; Hair follicle regeneration; Multilayer composite scaffold; Tissue engineering.