Impaired cutaneous wound healing is a major complication in elderly people and patients suffering from diabetes with raising rates in industrialized countries. Heterogeneity of clinical manifestations hampers effective molecular diagnostics and decisions for appropriate therapeutic regimens. Using a customized positional quantitative proteomics workflow, we have established a time-resolved proteome and N-terminome resource from wound exudates in a clinical pig wound model that we exploited as robust template to interpret a heterogeneous dataset from patients undergoing the same wound treatment. With Zyxin, IQGAP1 and HtrA1, this analysis and validation by targeted proteomics identified differential abundances and proteolytic processing of proteins of epidermal and dermal origin as prospective biomarker candidates for assessment of critical turning points in wound progression. Thus, we demonstrate the power of a fine-tuned animal wound model to bridge the translational gap as prerequisite for future extended clinical studies with large cohorts of individuals affected by healing impairments.