High prevalence of non-healing chronic wounds contributes to a huge healthcare burden across the world. Early treatment interventions for non-healing wounds are vital. Accumulation of 15% or more of senescent cells in a chronic wound edge has been shown to be an indicator that the wound is unlikely to heal. Determining the presence of senescent cells require invasive procedures such as tissue biopsies to be taken.
In this study, a strong correlation is drawn between decreased collagen area and presence of senescent cells in human chronic wounds i.e. venous leg ulcer (VLU), diabetic foot ulcer (DFU) and pressure ulcer (PRU). It is also reported that the lowest collagen levels were found in VLU patients less than 60 years of age, with a persistent wound of > 24 months.
Staining of nuclei, collagen and senescent cells of venous leg ulcer biopsies revealed a strong link between presence of senescent cells and collagen area. (a) Haematoxylin and eosin staining of nuclei (purple) and extracellular proteins (pink) in a venous leg ulcer. Montage of high-power images [1200 (W) × 1000 (H) μm] of an 8 μM cryosection thick—two from high senescence (HS) regions and two from low senescence (LS) regions of a venous leg ulcer taken using × 20 objective lens. (b) MT staining collagen (green), muscle and keratin (red) and cytoplasm (pink/red) in a sister section. Montage followed by (c) X-gal staining as a marker for senescent cells (senescent cells (blue), nuclei and cytoplasm (pink). Scale bar: 500 μm (montage) and 20 μm (high power). (d) SHG imaging of collagen (white) in × 20 for VLU and arm tissue. Scale bar: 200 μm. MT and X-gal images of the arm tissue are also shown. (e) Regression plots of collagen area (x-axis) against senescent cell number (y-axis) of individual patients of the VLU cohort. (f) Single regression plot of the VLU cohort.
Elevated levels of senescent cells were also found in VLU of males. Second harmonic imaging of collagen at the edge of chronic wounds with a handheld multiphoton device could be used to predict the number of senescent cells, indicating if the wound is on a healing trajectory or not. Data presented supports the use of collagen imaging in cutaneous wound assessment for a faster and non-invasive method to predict cellular senescence and determining wound trajectory of healing.
The use of physical assessments of the wound to determine which treatment methods to use often involves evaluating wounds without knowledge of the actual wound trajectory. The link established between presence of senescent cells and collagen area coupled with handheld two photon skin imaging could potentially serve as an indicator for the state of wound healing to denote if intervention is necessary.
The full article can be accessed here.
