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Restoration of sweat glands (SwGs) represents a great issue in patients with extensive skin defects. Recent methods combining organoid technology with cell fate reprogramming hold promise for developing new regenerative methods for SwG regeneration. Here, a practical strategy for engineering functional human SwGs in vitro and in vivo is provided. First, by forced expression of the ectodysplasin‐A in human epidermal keratinocytes (HEKs) combined with specific SwG culture medium, HEKs are efficiently converted into SwG cells (iSwGCs). The iSwGCs show typical morphology, gene expression pattern, and functions resembling human primary SwG cells. Second, by culturing the iSwGCs in a special 3D culturing system, SwG organoids (iSwGOs) that exhibit structural and biological features characteristic of native SwGs are obtained. Finally, these iSwGOs are successfully transplanted into a mouse skin damage model and they develop into fully functioning SwGs in vivo. Regeneration of functional SwG organoids from reprogrammed HEKs highlights the great translational potential for personalized SwG regeneration in patients with large skin defects. [ABSTRACT FROM AUTHOR]

Engineered Sweat Gland Organoids In article number 2103079, Tao Yue, Lei Dong, Xiaobing Fu, and co‐workers have converted human epidermal keratinocytes into cells with typical properties of sweat gland cells and obtained sweat gland organoids from these cells. Transplanting the organoids into mice successfully restored the vital sweat gland functions during skin wound healing, demonstrating a fast and robust way of personalized sweat gland regeneration in patients with large skin defects. [ABSTRACT FROM AUTHOR]

Transplanting the organoids into mice successfully restored the vital sweat gland functions during skin wound healing, demonstrating a fast and robust way of personalized sweat gland regeneration in patients with large skin defects. B Engineered Sweat Gland Organoids b In article number 2103079, Tao Yue, Lei Dong, Xiaobing Fu, and co-workers have converted human epidermal keratinocytes into cells with typical properties of sweat gland cells and obtained sweat gland organoids from these cells. [Extracted from the article]

Efficient wound repair with skin appendage regeneration following severe trauma poses a challenge due to the scarcity of skin grafts and decreased drug effectiveness in protease‐rich wound microenvironments. Here, a multifunctional artificial skin (NIR‐mFAS) with photothermal‐triggered drug delivery capabilities is designed to actively and comprehensively improve the regenerative potential of full‐thickness wounds. The antibacterial chitosan/silk fibroin hydrogel matrix of artificial skin, cross‐linked by electrostatic interactions, effectively encapsulates and sustains the release of epidermal growth factor (EGF) to accelerate re‐epithelialization and neovascularization by promoting the migration and proliferation of repair cells. Subsequently, the photothermal responsive polydopamine nanoparticles (PDA‐NPs) dispersed in the matrix enable precise control over the release of BMP4 under the irradiation of 1064 nm NIR, thereby inhibiting scarring by reducing myofibroblasts during the proliferative stage. Importantly, the concurrent controlled release of CHIR99021 can modulate cell fate by inducing the conversion of myofibroblasts into dermal papilla‐like cells, leading to hair follicle and sebaceous gland regeneration. The NIR‐mFAS functions as an advanced delivery system for achieving high‐quality wound healing with appendage regeneration and offers a smart therapeutic approach that can be applied to other treatments requiring coordinated delivery of multiple pharmacological agents. [ABSTRACT FROM AUTHOR]