Animal Models of Wound Healing Dynamics

Animal models have been indispensable for elucidating the cellular and molecular events that underlie tissue repair and regeneration. Rodents, particularly mice and rats, are most commonly employed owing to their genetic tractability, well characterised immune systems and cost-effectiveness. Acute excisional and incisional models mimic minor trauma and allow precise measurement of contraction, re-epithelialization and matrix remodelling. Splinted wound models in rodents reduce contraction artefacts and better approximate human healing by re-epithelialization. Chronic wound models incorporate pathological features such as diabetes, ischaemia or radiation injury to recapitulate impaired healing and persistent inflammation. Flap models, including axial or random pattern flaps, simulate complex tissue transfer, ischaemia-reperfusion and surgical complications. Transgenic and knock-out strains enable dissection of specific signalling pathways, while larger mammals (e.g., pigs) provide skin architecture more akin to humans for translational studies. Across these systems, investigators monitor angiogenesis, inflammatory cell infiltration, growth factor expression and biomechanical properties of the new tissue. A balanced selection of models ensures that findings advance both fundamental understanding and the development of therapies to address global challenges in wound care.

Research from Nature Portfolio

Recent studies have demonstrated that macrophage colony-stimulating factor (M-CSF) can induce a subset of haematopoietic cells to dedifferentiate into multipotent stem cells at wound sites. In a murine excisional skin model, application of M-CSF accelerated closure by enhancing the local pool of SSEA-positive stem cells, supporting epithelial and vascular regeneration. Neutralisation of M-CSF delayed repair, whereas transplantation of M-CSF-induced stem cells into wounds led to their integration and differentiation into skin-specific cell types, underlining the factor’s potential to augment endogenous regenerative responses.

Animal Models of Wound Healing Dynamics publication trend

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

Technical terms

Angiogenesis: formation of new blood vessels during healing processes.

Re-epithelialization: restoration of the epithelial layer over a wound.

Ischaemia-reperfusion: interruption of blood supply followed by its restoration, often causing tissue stress.

Granulation tissue: new connective tissue formed during wound repair, rich in vessels and fibroblasts.

Scratch assay: in vitro technique where a gap is introduced in a cell layer to assess cell migration.

Macrophage colony-stimulating factor (M-CSF): a cytokine that supports differentiation and function of macrophages and can induce dedifferentiation of certain blood cells into stem-like cells in wounds.

References

1. Accelerating skin wound healing by M-CSF through generating SSEA-1 and -3 stem cells in the injured sites. Scientific Reports (2016).
2. Exploring the Wound Healing Potential of Hispidin. Nutrients (2024).
3. Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing. Biological Procedures Online (2024).
4. Ischemia Impaired Wound Healing Model in the Rat—Demonstrating Its Ability to Test Proangiogenic Factors. Biomedicines (2023).