Immunohistochemical and Molecular Markers for Human Skin Wound Vitality and Wound-age Estimation (Postinfliction Interval)

Determining wound vitality and accurately estimating wound age remain fundamental yet challenging tasks in forensic pathology, particularly in cases with short survival times, advanced decomposition, or limited morphological clarity. Conventional gross and histological criteria often lack sensitivity and reproducibility, prompting increasing interest in immunohistochemical (IHC) and molecular approaches that reflect time-dependent biological responses to injury. This systematic review synthesizes human-based evidence on IHC and molecular markers applied to skin wounds for the assessment of wound vitality and postinfliction interval estimation. Analysis of the included studies demonstrates that several marker families show reproducible and biologically consistent time-dependent expression patterns. Early inflammatory and endothelial activation markers – such as cytokines, chemokines, selectins, and cyclooxygenase-2 – consistently provide strong evidence of wound vitality within minutes to hours after injury. Extracellular matrix-related markers and water channel proteins, particularly fibronectin and aquaporins, show robust performance in early to intermediate intervals and retain diagnostic utility under adverse forensic conditions. Macrophage-associated and enzymatic markers, including matrix metalloproteinases, exhibit peak expression in subacute phases, enabling discrimination between early and later wound-age categories. Early inflammatory and endothelial markers provide valuable information within hours after injury, while macrophage-associated and repair-related markers are more informative in subacute time windows. However, substantial heterogeneity in study design, scoring systems, antibody protocols, and reporting standards limits direct comparability and routine forensic implementation. This review is novel in systematically integrating time-dependent biological behavior with methodological robustness and translational readiness, thereby moving beyond marker listing toward practical forensic interpretation. The results support a multimarker, phase-oriented diagnostic strategy and highlight the need for standardized protocols, quantitative thresholds, and validation in real forensic casework to strengthen evidentiary reliability.