Hair-bearing human skin generated entirely from pluripotent stem cells

The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain1,2. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met3-9. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery

The radial forearm snake flap: An underutilized technique for fasciocutaneous and osteocutaneous forearm flaps with primary closure

Background: The radial forearm free flap (RFFF) is associated with troublesome donor site morbidity related to split thickness skin grafting (STSG). The radial forearm snake flap with primary closure of the donor site may reduce donor site complications. Methods: Single institution, retrospective cohort study comparing rates of delayed donor site wound healing and tendon exposure in 52 patients undergoing radial forearm snake flap and 95 patients undergoing conventional RFFF with STSG closure of the donor site. Results: Tendon exposure occurred in zero (0%) patients undergoing snake flap and four (4.2%) patients undergoing conventional RFFF (0/52 vs. 4/95; p = 0.297). Delayed wound healing occurred in zero (0%) patients undergoing snake flap and 19 (20.0%) patients undergoing conventional RFFF (0/52 vs. 19/95; p \u3c 0.001). Conclusions: The radial forearm snake flap provides an alternative to conventional RFFF harvest, which enables primary donor site closure with reduced rates of delayed donor site healing