Cellular senescence mechanisms in chronic wound healing

The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular cells,...

Following injury, the integrity of the injured tissues must be reestablished. For example, in skin tissue, wound repair involves coordination among resident skin cells, blood mononuclear cells, extracellular matrix, growth factors, and cytokines to complete the healing cascade.
Formation of Blood Clot
In case of deep injuries, trauma to blood vessels results in blood loss. In the meantime, phospholipids released from the ruptured endothelial cellular membrane are converted into arachidonic...

Complications during healing arise when tissue repair is altered by local or systemic factors. These changes involve abnormal collagen deposition, altered biomechanics, and reduced vascular supply, impairing restoration of normal structure and function.Loss of FunctionScar tissue differs significantly from the original tissue it replaces. In the skin, fibrosis lacks adnexal structures such as hair follicles, sebaceous glands, and sweat glands. Their absence reduces tactile sensitivity, impairs...

Cellular injury occurs when a cell cannot maintain homeostasis or adapt to stressors such as hypoxia, toxins, or trauma. Depending on severity and duration, injury may be reversible, allowing recovery, or irreversible, leading to cell death.General Mechanisms of Cell InjuryAlthough causes vary, most cellular injuries arise from a few key mechanisms that disrupt essential functions and often amplify one another. Cell survival depends on the extent and balance of these disturbances.ATP depletion...

Chronic inflammation is a prolonged, dysregulated immune response that persists for weeks to years when the inciting stimulus is difficult to eradicate or when self‑antigens drive ongoing reactivity. Morphologically, it is defined by mononuclear cell infiltration, progressive tissue destruction, and concurrent attempts at healing via angiogenesis and fibrosis. Compared with acute inflammation, edema is less prominent while cellular infiltration predominates; triggers include persistent...

Epidermal stem cells (EpiSCs) are mainly located at the basal layer of the epidermis. These cells repair minor injuries of the skin and replace dead skin cells. However, EpiSCs’ cannot heal severe wounds such as major burns or those from diabetes or hereditary disorders. In such cases, culturing the epidermal stem cells from the patient is possible and has yielded successful treatment options, such as laboratory-grown skin grafts. These grafts are synthesized using a patient’s own EpiSCs...