Growing interest is being given to the sensitization of flaps in the clinics. Although epineural coaptation with flaps was published decades ago, the method has not yet become the gold standard, and re-sensitization evaluation in patients is mainly done by clinical tests. These assessments are inherently subjective and depend heavily on the investigator. The aim of our study was to gain insight into the various methods used to assess re-sensitization of flaps in animal models. Subsequently, in a bench-to-bedside fashion, these methods could enrich future clinical trials by providing objective, patient- and investigator-independent outcome measures. A systematic search of PubMed, Embase, and the Cochrane Library was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Out of the 219 identified records, 15 studies involving a total of 421 animals met the inclusion criteria. Sensory testing was performed using either behavioral responses such as the cutaneous trunci muscle (CTM) reflex (3 studies, n=117), or immunohistochemical detection of sensory nerve markers including protein gene product 9.5 (PGP 9.5; 10 studies, n=225) and calcitonin gene-related peptide (CGRP; 9 studies, n=218). These tools offered measurable insights into reinnervation, although methodological variability limited direct comparisons. This review highlights the value of neuroprotein markers and behavioral tests in flap re-sensitization research. Standardization of these methods, along with the integration of proteomic approaches, could enhance the objectivity and translational relevance of future clinical studies.
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