ABSTRACT
We present a mathematical model to quantify parameters of mouse excisional wound healing from photographic data. The equation is a piecewise linear function in log scale that includes key parameters of initial wound radius (R0 ), an initial wound stasis phase (Ti ), and time to wound closure (Tc ); subsequently, these terms permit calculation of a latter active proliferative phase (Tp ), and the healing rate (HR) during this active phase. A daily photographic record of wound healing (utilizing 6 mm diameter splinted excisional wounds) permits the necessary sampling for robust parameter refinement. When implemented with an automated nonlinear fitting routine, the healing parameters are determined in an operator-independent (i.e., unbiased) manner. The model was evaluated using photographic data from a splinted excisional surgical procedure involving several different mouse cohorts. Model fitting demonstrates excellent coefficients of determination (R2 ) in each case. The model, thus, permits quantitation of key parameters of excisional wound healing, from initial wounding through to wound closure, from photographic data.
Subject(s)
Photography , Re-Epithelialization/physiology , Wound Healing/physiology , Wounds and Injuries/pathology , Animals , Disease Models, Animal , Mice , Mice, Inbred BALB C , Models, Theoretical , SplintsABSTRACT
Objective: To determine quantitative parameters of dermal wound healing senescence in aged BALB/cByJ mice (an important animal model of aging) and to evaluate the potential for therapeutic intervention by fibroblast growth factor-1 (FGF-1). Approach: Utilize a novel noninvasive fine-sampled photographic methodology to quantify wound healing parameters for healing phases from wounding through to wound closure. Results: Parameters associated with key healing phases were quantified and compared between nonaged and aged cohorts of both genders. The results identify a sexual dimorphism in dermal wound healing, with nonaged females exhibiting a greater overall healing efficiency than males. This enhanced healing in females, however, senesces with age such that healing parameters for aged males and females are statistically indistinguishable. Topical application of FGF-1 was identified as an effective therapeutic intervention to treat dermal healing senescence in aged females. Innovation: The FGF intervention is being analyzed using a new recently published model. This approach significantly increases the amount of preclinical animal data obtainable in wound healing studies, minimizes cohort number compared with (lethal) histological studies, and permits a direct statistical comparison between different healing studies. Conclusion: Quantitative parameters of dermal wound healing, obtained from noninvasive fine-sampled photographic data, identify topical FGF-1 as an effective therapeutic to treat the senescence of dermal healing present in aged female BALB/cByJ mice.
