Credit: Minku Kang, Unsplash
Comprehensive skin regeneration presents a significant clinical hurdle, impacting countless individuals globally and offering limited solutions. The quest for skin rejuvenation has been a long-standing pursuit, aiming to provide hope for burn victims, wounded soldiers, and those afflicted with skin ailments, all in pursuit of complete recovery. When it comes to treating full-thickness skin wounds, autologous skin grafting has historically been the go-to method, but its utility is restricted by the limited availability of harvestable skin. The grafts that are accessible are typically either transient or, if they are permanent, lack several key attributes of healthy skin, often resulting in a scarred appearance. The creation of full-thickness skin has remained unattainable thus far.
Bioprinting emerges as a promising alternative approach to producing skin substitutes, thanks to its ability to replicate the structural organization of natural skin into biomimetic layers in a controlled laboratory setting. A recent research paper published in Science Translational Medicine by scientists at the Wake Forest Institute for Regenerative Medicine (WFIRM) showcases a remarkable breakthrough in the development of bioprinted skin that accelerates wound healing, fosters the healthy remodeling of the extracellular matrix, and instills hope for comprehensive wound recovery.
This research entailed the bioprinting of all six primary human cell types found in skin, combined with specialized hydrogels as a bioink. This process resulted in the creation of multi-layered full-thickness skin that includes all three layers found in normal human tissue: the epidermis, dermis, and hypodermis.
When transplanted onto full-thickness wounds in nu/nu mice, the bioprinted skin with human cells facilitated swift vascularization and the formation of epidermal rete ridges, mirroring the native human epidermis, and maintaining a natural-looking extracellular matrix. Cell-specific staining confirmed the successful integration of implanted cells into the regenerated skin. Employing a similar strategy, a 5 centimeter–by–5 centimeter bioprinted autologous porcine skin graft was transplanted onto full-thickness wounds in a porcine excisional wound model. The bioprinted skin graft enhanced epithelialization, reduced skin contraction, and facilitated the normal organization of collagen, while also minimizing fibrosis. The analysis of differential gene expression revealed an increase in pro-remodeling protease activity in wounds transplanted with bioprinted autologous skin grafts.
Through the innovative use of existing bioprinting technology to address these limitations, the WFIRM team has demonstrated the feasibility of achieving fully functional skin regeneration. The bioengineered skin grafts now provide a triple-layered structure for comprehensive coverage of full-thickness wounds. These findings conclusively demonstrate the potential of bioprinted skin to support skin regeneration, facilitating nonfibrotic wound healing, and hinting at its viability for human clinical applications.
