Regenerative Mechanisms in Mammalian Wound Healing

Regenerative wound healing in mammals involves a coordinated sequence of events that restore tissue architecture and function with minimal scarring. Following an initial haemostatic response to control bleeding, an acute inflammatory phase recruits immune cells that clear debris and release signals directing repair. In certain contexts, notably in specialised strains or species, inflammation gives way to proliferation characterised by re-epithelialisation, neovascularisation and matrix remodelling. A transient mass of proliferating progenitor cells, the blastema, can form under permissive conditions, enabling de novo tissue patterning reminiscent of amphibian regeneration. Extracellular matrix (ECM) composition and dynamics play a central role, guiding cell migration, differentiation and growth factor gradients. Macrophage phenotypes, T cell subsets and secreted factors such as stromal-derived factor 1 (SDF1) modulate fibrotic versus regenerative outcomes. Epigenetic regulation and signalling pathways including Wnt, MAPK and TGF-β determine whether repair proceeds towards scar formation or true regeneration. Model systems such as African spiny mice and MRL/MpJ mice have revealed that reduced pro-inflammatory cytokine release, altered ECM deposition and enhanced progenitor activation underpin scar-free healing. Understanding these processes promises novel strategies to promote functional tissue restoration in clinical wound management and regenerative medicine.

Research from Nature Portfolio

Comparative analyses of ear-hole closure in spiny mice have demonstrated that blastema formation underlies complete tissue regeneration, whereas conventional laboratory mice form fibrotic scars despite similar injury sizes. Proteomic profiling of skin wounds in Acomys cahirinus versus Mus musculus has identified divergent enrichment of Wnt and MAPK signalling components, elevated matrix remodelling proteases and distinct arginase isoforms that favour regeneration. Detailed studies of skeletal muscle injury in spiny mice reveal accelerated fibre repair, reduced TGF-β signalling and enhanced embryonic myosin induction, highlighting intrinsic differences in ECM biomechanics and inflammatory modulation that enable chronic muscle regeneration without adipogenic replacement.

Regenerative Mechanisms in Mammalian Wound Healing publication trend

The graph below shows the total number of articles in regenerative mechanisms in mammalian wound healing across all publications each year (not limited to Nature Index journals).

Technical terms

Blastema: A mass of undifferentiated proliferative cells that forms at the injury site and gives rise to regenerated tissues.

Extracellular matrix (ECM): A complex network of proteins and glycosaminoglycans that provides structural support and biochemical cues during repair.

Macrophage: Innate immune cells that clear debris, release cytokines and adopt pro- or anti- inflammatory phenotypes influencing healing outcomes.

Epimorphic regeneration: Restoration of lost structures through blastema formation and patterning, as seen in certain mammalian and amphibian models.

SDF1 (stromal-derived factor 1): A chemokine that regulates progenitor cell recruitment and influences fibrotic versus regenerative healing pathways.

References

1. Macrophages are necessary for epimorphic regeneration in African spiny mice. eLife (2017).
2. Comparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals. Nature Communications (2016).
3. Aging Suppresses Skin-Derived Circulating SDF1 to Promote Full-Thickness Tissue Regeneration. Cell Reports (2018).
4. Perfect chronic skeletal muscle regeneration in adult spiny mice, Acomys cahirinus. Scientific Reports (2018).
5. Spiny mouse (Acomys): an emerging research organism for regenerative medicine with applications beyond the skin. npj Regenerative Medicine (2021).
6. Complex Tissue Regeneration in Mammals Is Associated With Reduced Inflammatory Cytokines and an Influx of T Cells. Frontiers in Immunology (2020).
7. Comparative Proteomic Analysis in Scar-Free Skin Regeneration in Acomys cahirinus and Scarring Mus musculus. Scientific Reports (2020).