Human nail bed-derived decellularized scaffold regulates mesenchymal stem cells for nail plate regeneration

Among hand trauma, nail bed is the most involved tissue in hospital emergency departments, resulting in the loss of nail plate, which leads to a disturbance of hand grasp function, long-lasting digit tip pain, hyperpathia, and disesthesia. Treatment of nail bed defects is a significant clinical challenge due to the lack of uniform nail bed thickness and distinct regenerative ability. In this study, it is shown that the extracellular matrix of decellularized nail bed scaffolds can play an important role in inducing bone mesenchymal stem cells to differentiate into nail epithelial cells. Using decellularized nail bed scaffolds combined with bone mesenchymal stem cells, it is revealed that the engineered nail bed can promote nude mouse nail plate regeneration ectopically. The natural extracellular matrix of decellularized nail bed scaffolds can serve as a 3D structural template for bone mesenchymal stem cell differentiation into nail-associated cells, initiating the nail plate regeneration. These results not only provide a proof-of-principle for the generation of transplantable nail grafts based on decellularized nail bed scaffolds derived from clinically wasted amputated fingers but also provide important considerations for clinical treatment for digit tip trauma.