Gradual Decline of Murine Digit Tip Regenerative Capacity Defined by Increased Amputation Extent

Abstract Objective: Digit tip amputation is among few cases of injury that may result in regenerative outcome in both mice and humans, making animal model more relevant for studying the phenomenon. Nevertheless, experimental studies in the field share a significant degree of variability and contrasting approaches for injury application. A reliable and relevant model of digit tip amputation that allows to induce both—regenerative and non-regenerative outcomes with minor differences of amputation level is a pivotal condition for data consistency in comparative studies. Methods: We have tested five amputation degrees in C57/B6 mice and have identified the most suitable and reproducible among them for future application in the field. Results: Basically, obligate non-regenerative healing can be induced only by entire nail amputation. In contrast, reproducible full-scale regeneration of digit tip demanded a significant part of the nail, bone and other tissues to be retained, while intermediate amputation extent demonstrated variable results with three possible outcomes: regeneration, incomplete regeneration and non-regenerative healing. Conclusions: Overall, we believe that our findings provide a valuable methodological insight for further investigations of digit tip regeneration mechanisms and provide a feasible model that would beneficially impact data integrity in the field.