Noninvasive device readouts validated by immunohistochemical analysis enable objective quantitative assessment of acute wound healing in human skin

Abstract

Objective evaluation of cutaneous wounds through use of noninvasive devices has important implications for diagnosis, monitoring treatment efficacy, progression and may lead to development of improved theranostic treatment strategies. However, there is a lack of validation in the use of certain devices in wound repair, where objective measurements taken by noninvasive devices have been corroborated by immunohistochemical analysis. Thus, data from three acute wound-healing studies in healthy volunteers using three noninvasive objective devices were further evaluated by immunohistochemistry. One hundred ten participants had 5-mm diameter skin biopsies to their arms. Spectrophotometric intracutaneous analysis (SIAscopy), full-field laser perfusion imaging, and three-dimensional imaging provided quantitative measurements of melanin, hemoglobin, collagen, blood flow, and wound size; all of which were validated by immunohistochemistry. Full-field laser perfusion imaging showed blood flow increased to D7 and decreased by 40% to D14. SIAscopy showed that hemoglobin increased to D7 and reduced to D14. CD31 analysis corroborated this by showing a 76% increase in blood vessel density to D7 and a reduction by 14% to D14. Three-dimensional imaging showed that wound surface area reduced by 50% from day 7 to day 14. Alpha-smooth muscle Actin (Alpha-SMA) staining supported these trends by showing increased levels by 72% from D0 to D14 (corresponding to wound contraction). Collagen, measured by SIAscopy, decreased to D7 and increased to D14, which was validated by collagen III analysis. Additionally, collagen I increased by 14% from D0 to D14. SIAscopy measurements for melanin showed an increase at D7 and a slight reduction to D14, while melanogenesis increased by 46.7% from D0 to D14. These findings show the utility of noninvasive objective devices in the quantitative evaluation of woundhealing parameters in human skin as corroborated by immunohistochemistry. This may contribute to the development of prognostic parameters for assessment of response to wound therapy.

Non‐animal models of wound healing in cutaneous repair: In silico, in vitro, ex vivo, and in vivo models of wounds and scars in human skin

“…These wounds are useful from an experimental perspective in that their size and depth can be precisely controlled. As they involve all the components of the healing process, they provide an excellent research tool and have been used to investigate angiogenesis, wound contraction, and wound closure . Numerous studies have been conducted evaluating various treatments for both wounds and scars using a sequential skin punch biopsy model to assess various characteristics and correlated by clinical measurements .…”

“…Ex vivo models enable immediate and short‐term evaluation of a particular effect on cells and its surrounding tissue components compared with in vivo models that provide direct analysis in the live human subject before, during and after exposure to a stimulus . Human in vivo models are useful as the pathology and physiology of healing is identical to that found in the patient . Both patient and volunteer models have their advantages and limitations.…”

“…Both patient and volunteer models have their advantages and limitations. Patient models allow assessment in a variety of wound or scar types, whilst volunteer models only enable evaluation of one type of wound or a similarly induced scar . Despite clear advantages, there remains a lack of standardisation and conformity in design, evaluation and follow‐up, for all wound types including acute, chronic wounds, and scars.…”

Non‐invasive objective devices for monitoring the inflammatory, proliferative and remodelling phases of cutaneous wound healing and skin scarring

“…The Moor full‐field laser perfusion imager (Moor FLPI‐2) (Moor Instruments Ltd, Axminster, UK) has also been used in wound healing trials . A study using this device also correlated the results taken from three acute punch biopsy wound healing studies and showed that these data were comparable to CD31 immunohistochemistry results .…”

“…However, the sample size was low, which means that their results should be interpreted with caution. SIAscopy has also been compared with immunohistochemistry from the tissue biopsies in an acute wound healing model . The collagen, melanin and haemoglobin results taken from the device were compared to collagen I, collagen III, Masson Fontana and CD31 staining, which showed that the data correlated well.…”