Pathophysiology-guided biomarkers and therapeutics for precision trauma medicine in polytrauma with musculoskeletal injuries

Polytrauma with predominant musculoskeletal (MSK) injury, resulting from blast, blunt, and crush mechanisms, remains a leading and complex challenge in both military and civilian medicine. These injuries not only disrupt tissues structurally but also trigger systemic cascades involving immune imbalance, endothelial dysfunction, mitochondrial stress, and premature cellular senescence. Such pathological processes contribute to both immediate clinical instability and long-term complications such as fibrosis, aberrant bone formation, neuroinflammation, and chronic disability. Conventional injury assessments, which rely heavily on anatomical scoring and nonspecific blood markers, fail to capture the dynamic molecular landscape underlying these conditions. To address this critical gap, we performed a comprehensive scoping review integrating evidence from basic science, translational studies, and clinical research published between January 2000 to June 2025, with particular emphasis on recent advances. The review highlights the discovery and validation of emerging blood-based and molecular biomarkers, including fatty acid-binding protein 3, syndecan-1, galectin-3, and trauma-associated microRNAs, as well as innovative diagnostic paradigms such as wearable biosensors, minimally invasive liquid biopsy platforms, and artificial intelligence (AI)-driven analytics. Unlike prior reviews, our analysis uniquely integrates findings across both military and civilian trauma contexts, providing actionable frameworks for clinical application. Building on these insights, we outline a practical roadmap: 1) deploy integrated multi-marker panels for early risk stratification, 2) expand inclusive trauma biobanking to capture diverse injury phenotypes, and 3) use adaptive, data-driven tools for real-time triage and personalized intervention. This approach links acute systemic responses to downstream recovery and rehabilitation, offering actionable guidance for both military and civilian trauma systems.