The burn repair molecule? Evaluating FGF-21 in thermal injury - A systematic review

Severe burns induce a hypermetabolic and inflammatory state, impairing wound healing and contributing to long-term morbidity. Fibroblast growth factor 21 (FGF-21), a metabolic hormone regulating lipid oxidation, glucose uptake, and mitochondrial homeostasis, has emerged as a potential biomarker and therapeutic modulator in critical illness. This systematic review followed PRISMA 2020 guidelines and assessed seven studies (2015-2024) published until April 2025. Clinical, in vivo, and in vitro investigations were included. Methodological quality was evaluated using the Level of Evidence, Newcastle-Ottawa Scale, and the SYRCLE Risk of Bias tool. In our study, FGF-21 was commonly upregulated following burn injury and was associated with hypermetabolism, adipose tissue browning, mitochondrial stress, and systemic inflammation. Nutritional interventions, including hydrolyzed collagen and omega-3 fatty acids, reduced FGF-21 levels, improved wound healing, and attenuated inflammatory responses. Preclinical models demonstrated that administration of exogenous FGF-21 enhanced re-epithelialization, angiogenesis, mitochondrial function, and anti-inflammatory signaling pathways. Conversely, chronically elevated endogenous FGF-21 levels were consistently linked to metabolic exhaustion, liver dysfunction, and impaired recovery. Overall, FGF-21 may be a promising diagnostic and therapeutic target in burn care. Its clinical relevance and long-term effects require further investigation for successful integration into clinical practice.