Bioprinting Skin with Hair Follicles
In that part of the tissue engineering community concerned with trying to reproduce natural skin structure, as best as possible with present technology, bioprinting is currently largely used for research and development rather than directly in clinical application as a regenerative therapy. For example, skin models are used in the screening and testing of topical therapies, and greater fidelity with natural skin gives more relevant information. Skin is a complex structure, in which cells associated with sweat glands and hair follicles appear to be important in coordinating growth and healing. The work noted here is an example of the state of the art in bioprinted skin; it remains to be seen as to the timeline for widespread use in the clinic.
Human skin comprises three major compartments, the hypodermis, the dermis, and the epidermis, each representing a rich cellular and biomolecular diversity. The skin also contains adnexal structures, such as the pilosebaceous unit, which is formed by the hair follicle and sebaceous gland. The pilosebaceous unit is further connected to the sweat apocrine gland, the arrector pili muscle, the underlying vasculature and is in contact with nerve cells. This complex structure is formed by about 15 types of cells distributed in concentric layers of cells of epithelial and mesenchymal origins.
Through life, different skin stem cell populations support the cyclic regeneration of the hair follicle and sebaceous gland. At the base of the hair follicle unit, the dermal papilla region is populated by cells known as dermal papilla cells (DPCs). These cells have a stem cell-like profile that allows the continuous and cyclic regeneration of the hair follicles. This characteristic is also part of the reason why the hair follicle units continue producing fibers in vitro. Furthermore, besides being an important route of chemical penetration into the skin, the pilosebaceous unit plays a crucial role in wound healing by providing cells that migrate into the damaged area and differentiate into the specific epidermal cells, demonstrating the relevance of this structure in skin tissue models for both permeation studies and in regenerative medicine as grafts.
Current approaches fail to adequately introduce complex adnexal structures such as hair follicles within tissue engineered models of skin. Here, we report on the use of 3D bioprinting to incorporate these structures in engineered skin tissues. Spheroids, induced by printing dermal papilla cells (DPCs) and human umbilical vein cells (HUVECs), were precisely printed within a pregelled dermal layer containing fibroblasts. The resulting tissue developed hair follicle-like structures upon maturation, supported by migration of keratinocytes and melanocytes, and their morphology and composition grossly mimicked that of the native skin tissue. Reconstructed skin models with increased complexity that better mimic native adnexal structures can have a substantial impact on regenerative medicine as grafts and efficacy models to test the safety of chemical compounds.