Towards Better Bioprinted Skin, Created and Applied During Surgery
Skin is a complex organ of many distinct layers, in which different cell types and structures interact to maintain function and ability to regenerate. Creating a skin-like structure is one thing, but introducing sweat glands, hair follicles, and other complex features is quite another. Still, the accessibility of skin and the frequency of serious injuries that remove large sections of skin makes the skin a good testbed for the development of improved bioprinting techniques that are capable of inserting complex small-scale structures, manufacturing the different layers of skin, and that can be used in situ, directly printing into the injured area. If complex features of skin can be assembled via 3D printing and proven in the clinic, then it is the hope that the techniques involved can be adapted for the regeneration of other organs.
"Reconstructive surgery to correct trauma to the face or head from injury or disease is usually imperfect, resulting in scarring or permanent hair loss. With this work, we demonstrate bioprinted, full thickness skin with the potential to grow hair in rats. That's a step closer to being able to achieve more natural-looking and aesthetically pleasing head and face reconstruction in humans." While scientists have previously 3D bioprinted thin layers of skin, this team is the first to intraoperatively print a full, living system of multiple skin layers, including the bottom-most layer or hypodermis. Intraoperatively refers to the ability to print the tissue during surgery, meaning the approach may be used to more immediately and seamlessly repair damaged skin. The top layer - the epidermis that serves as visible skin - forms with support from the middle layer on its own, so it doesn't require printing.
The hypodermis, made of connective tissue and fat, provides structure and support over the skull. "The hypodermis is directly involved in the process by which stem cells become fat. This process is critical to several vital processes, including wound-healing. It also has a role in hair follicle cycling, specifically in facilitating hair growth."
The researchers started with human adipose, or fat, tissue obtained from patients undergoing surgery. The team extracted the extracellular matrix - the network of molecules and proteins that provides structure and stability to the tissue - to make one component of the bioink. The team also obtained stem cells, which have the potential to mature into several different cell types if provided the correct environment, from the adipose tissue to make another bioink component. Each component was loaded into one of three compartments in the bioprinter. The third compartment was filled with a clotting solution that helps the other components properly bind onto the injured site. "The three compartments allow us to co-print the matrix-fibrinogen mixture along with the stem cells with precise control. We printed directly into the injury site with the target of forming the hypodermis, which helps with wound healing, hair follicle generation, temperature regulation, and more."