Adipose-Based Therapeutics and Transplantation of Hypodermis

<b>Significance:</b> Wound healing is a complex process, and while the epidermis and dermis receive significant attention, the role of the hypodermis is important. The adipose-rich hypodermis or subcutaneous layer supports overall skin function, and loss or injury can impair wound healing, result in adhesions and/or contracture, and restrict soft-tissue mobility. Traditional wound management methods are often insufficient for hypodermal injuries, necessitating innovative approaches. <b>Recent Advances:</b> Hypodermal adipose-based solutions, including fat grafting and stem cell therapies, show promise for reconstruction. Fat grafting enhances soft-tissue bulk and contour, enhances mechanical properties, and promotes angiogenesis, offering versatility in addressing a range of wound scenarios, including challenging cases. Adipose-derived stem cells exhibit regenerative potential, modulate inflammation, and facilitate tissue repair, making them valuable for scar revision, skin rejuvenation, and managing chronic wounds. Acellular adipose derivatives, such as exosomes and liquid extracts, contain bioactive molecules that support tissue regeneration and collagen production. Adipose-derived acellular extracellular matrix holds promise in wound healing by enhancing cell behavior and angiogenesis. <b>Critical Issues:</b> In this review, we will discuss adipose-centered options for improvement of wound healing and for restoration of the hypodermis together as a cluster of efficient and cost-effective wound management in cases of complex soft-tissue injuries. <b>Future Directions:</b> These innovative therapies, while requiring further research, hold significant potential to simplify procedures, reduce costs, and improve the quality of life for patients facing challenging wounds.