Cytokine Expression Pattern and Protein-Protein interaction network analysis of Leucocyte Rich Platelet Rich Fibrin and Injectable Form of Platelet Rich Fibrin

Purpose Platelet-rich fibrin (PRF) such as leucocyte-rich PRF (L-PRF) and injectable form of PRF (i-PRF) are widely used in various surgical applications. L-PRF- and i-PRF-derived cytokine variations and functional pathways are still unexplored. The aim of the study was to evaluate the expression pattern of Th1-, Th2-, and Th17-related cytokines by L-PRF and i-PRF under in vitro. Methods Cytokine levels were evaluated using multi-analyte ELISArray kit. Using elevated level of cytokines, the protein-protein interaction and pathway were predicted by computational method. Results The expressed cytokine levels were higher in L-PRF than in i-PRF. Specifically in L-PRF, IL8, IL2, IL6, and IL1A were expressed abundantly, whereas IL4, IL10, and IL6 were significantly high in i-PRF. Furthermore, protein-protein interaction (PPI) networks (cytokine-cytokine interactions) and pathway analyses were predicted using higher-order cytokines. PPI networks and gene ontology enrichment analysis showed functional variations between L-PRF and i-PRF. Kyoto Encyclopedia of Gene and Genome pathway analysis found that L-PRF mediates NF-k B signaling, Toll-like receptor signaling (TLR), and MAPK signaling via T-cell receptor signaling pathway. i-PRF is significantly involved in JAK-STAT signaling pathway through upregulation of STAT1. Conclusion Our study concludes that L-PRF and i-PRF act via different pathways that confirm functional variations between them. Therefore, we speculate that L-PRF may be effective in acute phase of chronic wounds such as in diabetes mellitus and immunocompromised patients whereas i-PRF may have a better outcome in acute wounds.