Stress and Wound Healing: Biopsychosocial Mechanisms Linking Neuroendocrine Dysregulation to Delayed Tissue Repair—A Narrative Review

Stress is increasingly recognized as a clinically relevant modifier of tissue repair, yet its effects on wound healing cannot be explained by a single endocrine or immune pathway. Psychological distress, pain, surgical trauma, social adversity, sleep disruption, and chronic disease may converge on the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic–adrenomedullary signaling, local neurocutaneous pathways, immune-cell function, redox balance, angiogenesis, fibroblast activity, extracellular-matrix turnover, and health-related behaviors. This narrative review examines the biopsychosocial mechanisms through which acute and chronic stress can delay wound healing and discusses the implications for surgical wounds, experimental wounds, and chronic non-healing wounds. A structured narrative search of PubMed, Scopus, and Web of Science and citation tracking of key reviews and primary studies was used, with emphasis on peer-reviewed human, translational, and mechanistic evidence relevant to stress biology and wound repair. Human studies consistently demonstrate that caregiving stress, academic examination stress, hostile interpersonal interactions, elevated perceived stress, and preoperative distress are associated with slower healing or dysregulated local wound mediators. Mechanistically, excessive or poorly regulated glucocorticoid signaling can suppress early pro-inflammatory cytokines, impair leukocyte trafficking, fibroblast proliferation, collagen deposition, angiogenesis, and re-epithelialization, whereas sympathetic activation and catecholamines can alter vascular tone and adrenergic signaling within the wound microenvironment. Stress also influences macrophage function, neuropeptide signaling, oxidative stress, pain, sleep, nutrition, treatment adherence, and social behavior. In chronic wounds, these pathways become bidirectional: the wound itself generates pain, odor, exudate, functional impairment, and social isolation, which can sustain psychological distress and neuroimmune dysregulation. Psychological and behavioral interventions, including relaxation with guided imagery, mindfulness-based approaches, expressive writing, and social support, show promising but heterogeneous effects and should be viewed as adjuncts rather than substitutes for evidence-based wound care. Integrating stress assessment and biopsychosocial management into wound-care pathways may improve recovery, particularly in patients with high psychological burden or chronic comorbidity.