In Vivo Models Of Frostbite: A Systematic Review Of Interventions And Outcome Metrics
Year: 2026
Type: conference-paper
Study design: Systematic Review
Abstract: PURPOSE: Frostbite is a severe cold-induced injury characterized by ischemia, necrosis, and long-term morbidity. Standardizing experimental models is difficult because frostbite arises from overlapping pathophysiologic phases and is influenced by freezing rate, tissue type, thaw-refreeze cycles, and anatomical variability. Models often yield inconsistent depth and extent of injury, while clinical frostbite is inherently heterogeneous and long-term sequelae such as neurovascular damage and pain are challenging to reproduce. Together, these factors make cross-study comparisons difficult and point to the necessity of assessing models that replicate frostbite wound healing and regeneration. To our knowledge, this is the first review to comprehensively evaluate frostbite wound healing in animal models, focusing on the experimental approaches and outcomes used to study tissue repair and regeneration. METHODS: A systematic literature search identified in vivo frostbite studies that tested therapeutic interventions and reported wound healing or regeneration outcomes. Extracted variables included animal species, number and weight of animals, method of frostbite induction, anatomical site of injury, therapeutic type, outcome measures, and any discussion regarding the experience or limitations of using the model. RESULTS: Of 963 studies screened, 25 met inclusion criteria. Rats (13) and mice (10) were most frequent, with fewer rabbit models (3), which have not been employed in recent literature. On average, 41 animals (range: 16-96) were used per study. Reported weights ranged from 18-25 g in mice, 174-300 g in rats, and 3-3.5 kg in rabbits. Frostbite was most often induced by contact freezing, with nine studies each using plates at −80 °C (dry ice) or −196 °C (liquid nitrogen). Less common methods included ethanol-water immersion (n=3), liquid nitrogen immersion (n=1), nitrogen gas jets (n=1), and one low-temperature exposure model. Therapeutic categories included natural/herbal extracts (n=5), biological/cell-based (n=4), synthetic/nanomaterials (n=6), conventional pharmacologics (n=5), and physical/energy-based modalities (n=2); one study used autologous tissue transfer (split thickness skin graft and flap). Macroscopic assessment of wound closure was nearly universal, joined by histopathological analyses (H&E and Masson's trichrome) for granulation, inflammation, fibroblast maturation, and re-epithelialization; CD31-based quantification of neovascularization and molecular assays for angiogenesis or inflammation were reported in roughly a third of studies. Standardized reporting of injury method and animal characteristics was present in 68% of studies, but randomization or blinding was explicitly described in just 20%. Few studies (12%) provided critical reflection on model limitations or translational applicability. CONCLUSION: In vivo frostbite models are heterogeneous but consistently emphasize wound closure and histopathological recovery as core outcomes. Rapid freezing at −196 °C induces more severe and less physiologically representative tissue damage compared to freezing at −80 °C, which offers a slower, more naturalistic cooling process that better simulates the gradual tissue injury observed in human frostbite cases. Rodents dominate due to availability and cost, while rabbits allow multiple injuries per animal and larger species may better replicate human responses. No single model can yet be recommended; selection should align with study aims, balancing feasibility, transferability, and ethics. *Source: https://ps-rc.org/meeting/Program/2026/EP103.cgi*
Language: English
Topic: Wound Healing and Treatments
Subfield: Rehabilitation
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7160651379