2020
DOI: 10.1136/bmjdrc-2019-000974
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Non-invasive monitoring of pharmacodynamics during the skin wound healing process using multimodal optical microscopy

Abstract: ObjectiveImpaired diabetic wound healing is one of the serious complications associated with diabetes. In patients with diabetes, this impairment is characterized by several physiological abnormalities such as metabolic changes, reduced collagen production, and diminished angiogenesis. We designed and developed a multimodal optical imaging system that can longitudinally monitor formation of new blood vessels, metabolic changes, and collagen deposition in a non-invasive, label-free manner.Research design and me… Show more

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Cited by 17 publications
(16 citation statements)
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“…Because they do not account for the effect of light propagation on fluorescence decay, macro-FLI imagers are well suited for imaging of superficial tissues and/or transparent systems, as in both cases scattering is minimal. Macro-FLI imagers have also been used for ex vivo whole-organ imaging (Kantelhardt et al, 2016;Papour et al, 2013) and for imaging of the skin in studies of melanoma (Seidenari et al, 2013), pigmentation (Dancik et al, 2013) and wound healing (Rico-Jimenez et al, 2020), as well as to assess nanoparticulate zinc oxide sunscreen safety (Mohammed et al, 2020) and living dermal equivalents (Meleshina et al, 2018).…”
Section: Contrast Enhancement For High-performance 3d Imaging and Super-resolution Microscopymentioning
confidence: 99%
“…Because they do not account for the effect of light propagation on fluorescence decay, macro-FLI imagers are well suited for imaging of superficial tissues and/or transparent systems, as in both cases scattering is minimal. Macro-FLI imagers have also been used for ex vivo whole-organ imaging (Kantelhardt et al, 2016;Papour et al, 2013) and for imaging of the skin in studies of melanoma (Seidenari et al, 2013), pigmentation (Dancik et al, 2013) and wound healing (Rico-Jimenez et al, 2020), as well as to assess nanoparticulate zinc oxide sunscreen safety (Mohammed et al, 2020) and living dermal equivalents (Meleshina et al, 2018).…”
Section: Contrast Enhancement For High-performance 3d Imaging and Super-resolution Microscopymentioning
confidence: 99%
“…A valid solution is represented by NLO microscopy techniques which allow to perform label-free, vital and three-dimensional observations in biological specimens, from in vitro samples to preclinical in vivo models and, potentially, to clinical applications. In the last 30 years, NLO microscopy techniques have been applied to a broad range of biomedical problems, such as tumor infiltration and growth ( Lu et al, 2015 ; Gavgiotaki et al, 2017 ; De Bortoli et al, 2018 ; You et al, 2018 ; Sun et al, 2019 ), stem cell differentiation and proliferation ( Quinn et al, 2013 ; Meleshina et al, 2016 , 2017 ), tissue regeneration ( Yu et al, 2012 ) and repair ( Huemer et al, 2017 ; Rico-Jimenez et al, 2020 ). In Figure 3A a schematic representation of a NLO microscope in inverted configuration, in which the excitation light irradiates the sample from the bottom to the top.…”
Section: Biological Applicationsmentioning
confidence: 99%
“…This system is based on a thin layer of skin stretched and encaged between two glasses, thus creating a window that allows optical accessibility to monitor tissue growth over time, and minimizing animal movement and ensuring repetitive analysis in the same area of the sample. A time-dependent analysis of scar tissue formation after superficial dorsal wounding, has been presented by Rico-Jimenez et al (2020) . A comparative preclinical analysis of diabetic mouse model exposed to placebo, low and high dose of drug (hypoxia-inducible factor coupled with prolyl hydroxylase inhibitor) allowed to reveal, via TPEF-FLIM and SHG microscopy, wound healing, angiogenesis, and metabolic behavior differences among cell populations in the injured site at different time points.…”
Section: Biological Applicationsmentioning
confidence: 99%
“…Multimodal microscopy has been suggested to overcome limitations of single-modal microscopy by enlarging the number bio-hallmarks monitored 1 , 2 , 21 , 32 , 41 43 and was so far shown to enable simultaneous imaging of angiogenic and metabolic changes, collagen synthesis, and wound closure. However, previous multimodal studies of wound healing utilized labels that may disturb the specimen 32 , 42 , stitched adjacent FOVs affecting the spatial analysis 42 , 43 , captured small FOVs 2 , 21 , 32 , 41 or a fraction of the healing course after wound infliction 21 , 32 , 43 , or suffered from poor or unequal resolution and co-registration of the modalities 2 , 41 .…”
Section: Introductionmentioning
confidence: 99%
“…Multimodal microscopy has been suggested to overcome limitations of single-modal microscopy by enlarging the number bio-hallmarks monitored 1 , 2 , 21 , 32 , 41 43 and was so far shown to enable simultaneous imaging of angiogenic and metabolic changes, collagen synthesis, and wound closure. However, previous multimodal studies of wound healing utilized labels that may disturb the specimen 32 , 42 , stitched adjacent FOVs affecting the spatial analysis 42 , 43 , captured small FOVs 2 , 21 , 32 , 41 or a fraction of the healing course after wound infliction 21 , 32 , 43 , or suffered from poor or unequal resolution and co-registration of the modalities 2 , 41 . While these studies extracted quantitative information of the imaged bio-hallmarks, the yielded wound healing models simplified the analysis by dividing the affected tissue area in separated zones, by describing the healing events separately, by missing remote aspects at far distances or late time points, or by omitting an equalized mathematical description of the hallmark’s processes.…”
Section: Introductionmentioning
confidence: 99%