Pathogenesis of wound healing disorders in the elderly

Makrantonaki, Evgenia; Wlaschek, Meinhard; Scharffetter‐­Kochanek, Karin

doi:10.1111/ddg.13199

Cited by 54 publications

(66 citation statements)

References 114 publications

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“…Its product, β-Galactosidase, is regarded as an established senescence marker. Cellular senescence constitutes a concomitant element in chronic wounds, as keratinocytes from aged humans show β-Galactosidase activity four times higher than cells from younger donors [63,64]. Additionally, senescent keratinocytes in chronic wounds are characterized by p21 up-regulation [65].…”

Section: Discussionmentioning

confidence: 99%

Human Skin Keratinocytes on Sustained TGF-β Stimulation Reveal Partial EMT Features and Weaken Growth Arrest Responses

Liarte

Bernabé‐García

Nicolás

2020

Cells

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Defects in wound closure can be related to the failure of keratinocytes to re-epithelize. Potential mechanisms driving this impairment comprise unbalanced cytokine signaling, including Transforming Growth Factor-β (TFG-β). Although the etiologies of chronic wound development are known, the relevant molecular events are poorly understood. This lack of insight is a consequence of ethical issues, which limit the available evidence to humans. In this work, we have used an in vitro model validated for the study of epidermal physiology and function, the HaCaT cells to provide a description of the impact of sustained exposure to TGF-β. Long term TGF-β1 treatment led to evident changes, HaCaT cells became spindle-shaped and increased in size. This phenotype change involved conformational re-arrangements for actin filaments and E-Cadherin cell-adhesion structures. Surprisingly, the signs of consolidated epithelial-to-mesenchymal transition were absent. At the molecular level, modified gene expression and altered protein contents were found. Non-canonical TGF-β pathway elements did not show relevant changes. However, R-Smads experienced alterations best characterized by decreased Smad3 levels. Functionally, HaCaT cells exposed to TGF-β1 for long periods showed cell-cycle arrest. Yet, the strength of this restraint weakens the longer the treatment, as revealed when challenged by pro-mitogenic factors. The proposed setting might offer a useful framework for future research on the mechanisms driving wound chronification.

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Section: Discussionmentioning

confidence: 99%

Human Skin Keratinocytes on Sustained TGF-β Stimulation Reveal Partial EMT Features and Weaken Growth Arrest Responses

Liarte

Bernabé‐García

Nicolás

2020

Cells

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“…In addition, chronic ulcers contained large percentage of pathogenic microorganisms such as Staphylococcus and Pseudomonas species. These types of pathogenic microorganisms secrete toxins, adhesion molecules, and surface complexes, causing cytotoxicity to the wound and subsequently affecting the healing (Makrantonaki, Wlaschek, & Scharffetter‐Kochanek, 2017). The synergistic effect of AM with antibiotics against microbial growth and biofilm formation was proved previously (Yadav, Go, Kim, Chae, & Song, 2017).…”

Section: Discussionmentioning

confidence: 99%

The use of irradiated amnion dressing for the treatment of antibiotic‐disinfected skin ulcer

Radwan

Nemr

2020

J Tissue Eng Regen Med

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Skin ulcers are non‐healed wounds caused by inflammation of epidermis up to the dermis, which causes pain and limits body movements, significantly reducing quality of life. Amniotic membrane is a placental collagenous biomaterial with many biological and mechanical properties important for tissue engineering and regenerative medicine. The aim of this work is to evaluate the efficacy of topical antibiotic washing followed with irradiated human amniotic membrane (iHAM) dressing for treating five different types of ulcers. The current study included 15 patients who were recruited from the outpatient clinic of the Egyptian Atomic Energy Authority. Follow up of all treated cases that completed the regimen was up to 3 months. The clinical progression of all treated ulcers was quantitatively evaluated by computerized estimation of the wound size reduction based on 3D image analysis. All cases in this study showed great outcomes within several weeks of treatment depending on wound infection, ulcer depth and size, period of healing disorder, age, blood glycemia, and other clinical criteria. Patients' questionnaires revealed that pain was controlled by the first time of treatment. After 1 week post‐treatment, granulation tissue was generated and observed in all patients, and all microbial colonies have been eliminated from wounds with previous infection. The current study indicated that the dressing of ulcers with iHAM induces fast healing without complication.

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“…However, their usefulness is limited in elderly males with atrophic bald scalps. Furthermore, patients suffering from chronic wounds are often of advanced age and have multiple comorbidities that disqualify them from major surgical interventions . Suction blister epidermal grafting (SBEG) was introduced by Kiistala and Mustakallio in 1964, and has been successfully applied in the treatment of chronic wounds, leg ulcers and vitiligo .…”

Section: Introductionmentioning

confidence: 99%