Physiologic impact of inflammation in the polytrauma patient

Abstract Polytrauma represents one of the most challenging scenarios in modern trauma care, with fracture healing outcomes that defy conventional expectations. Although isolated fractures typically follow predictable healing patterns, the presence of multiple injuries creates complex interactions that can either accelerate or severely impair bone regeneration. Remarkably, patients with traumatic brain injury often demonstrate enhanced fracture healing with rapid callus formation and shorter time to union, whereas those with systemic inflammatory burden from thoracic or multiorgan trauma frequently experience delayed healing and complications. These paradoxical outcomes reflect distinct biological pathways that are only beginning to be understood. Malnutrition, affecting up to one-third of hospitalized orthopaedic patients, further complicates recovery by impairing both soft tissue and bone healing. Emerging research has identified key molecular mediators including complement factors, inflammatory cytokines, and potentially leptin as critical determinants of healing trajectories. However, translating these laboratory findings into clinical practice remains challenging because of the heterogeneous nature of polytrauma populations and the complexity of coordinating multicenter research. The purpose of this review is to synthesize current understanding of nutritional optimization strategies in polytrauma, delineate the molecular mechanisms underlying both accelerated and delayed fracture healing, explore the unique effects of traumatic brain injury on bone regeneration, and describe the development of collaborative research infrastructure necessary to advance the field.