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Abstract
Significance: Chronic wounds, such as diabetic foot ulcers, venous stasis ulcers,
and pressure ulcers affect millions of Americans each year, and disproportionately
afflict our increasingly older population. Older individuals are predisposed to wound
infection, repeated trauma, and the development of chronic wounds. However, a complete
understanding of how the attributes of aging skin affect the wound healing process
has remained elusive. Recent Advances: A variety of studies have demonstrated that
the dermal matrix becomes thinner, increasingly crosslinked, and fragmented with advanced
age. These structural changes, as well as an increase in cell senescence, result in
altered collagen fiber remodeling and increased stiffness. Studies combining mechanical
testing with advanced imaging techniques are providing new insights into the relationships
between these age-related changes. Emerging research into the mechanobiology of aging
and the wound healing process indicate that the altered mechanical environment of
aged skin may have a significant effect on age-related delays in healing. Critical
Issues: The interpretation and synthesis of clinical studies is confounded by the
effects of common comorbidities that also contribute to the development of chronic
wounds. A lack of quantitative biomarkers of wound healing and age-related changes
makes understanding structure–function relationships during the wound healing process
challenging. Future Directions: Additional work is needed to establish quantitative
and mechanistic relationships among age-related changes in the skin microstructure,
mechanical function, and the cellular responses to wound healing.