A WORLD WITHOUT SCARS: Regenerating wounded skin rather than patching with scars

2026-07-22

Scars are a mystery. They rarely develop in lower vertebrates, where the norm is a complete regeneration of damaged tissues, but are frequent in mammals including humans. Scar phenotypes depend on different injury types, anatomic locations, age, gender and species. The natural diversity of scars includes rare cases, where damaged tissues regenerate without scarring. The scar/regeneration decision remains unresolved and scar prevention is a clinical challenge. Current research has been held up by conceptual and operational bottlenecks. The current conceptual notion comes from experiments showing that scarring depends on the internal environment of the injured organ. I challenged this notion by uncovering specialized fibroblast cell lineages that regenerate connective tissues without scars, anywhere, anytime. My hypothesis is that the decision to scar/regenerate lies in the compositions of specific fibroblast types. To further study this theory I had to resolve a second bottleneck, the current lack of assays that display the full complexity of scarring and regeneration. I have thus developed innovative technological approaches (four novel tools) that allow whole-animal live imaging, tracking and gene modification of fibroblasts. Building on these innovative tools and my expertise in cell lineages as linchpins of this proposal, I aim to: (1) catalogue the repertoires of dermal fibroblast lineages, (2) image their dynamics during scarring/regeneration (3) identify the decision-making genes for scarring/regeneration in actual skin tissues, and finally (4) translate our findings from mouse to human skin. This new notion that specialized fibroblast lineages drive scarring/regeneration, combined with the technology breakthroughs, will greatly advance our current understanding of scar formation, which is a significant worldwide biomedical problem, creating new research avenues for regenerative medicine far beyond the current state-of-the-art.

Germany

2025-11-01