BIOLOGICAL BASIS OF THE USE OF LEUKOCYTE - PLATELET RICH FIBRIN (L - PRF) IN THE HEALING OF TYMPANIC MEMBRANE PERFORATIONS: A REVIEW OF THE ROLES OF IL-1Β, FGF, FIBROBLASTS, KERATINOCYTES, AND COLLAGEN REMODELING

Abstract

The healing of tympanic membrane perforations (TMP) is a complex biological process involving sequential phases of inflammation, proliferation, and tissue remodeling. During the early inflammatory phase, interleukin-1 beta (IL-1β) plays a crucial regulatory role in initiating the inflammatory cascade and coordinating immune responses. In the proliferative phase, fibroblast growth factor (FGF) contributes significantly to cellular proliferation, angiogenesis, and extracellular matrix formation. The activity of fibroblasts and the migration of keratinocytes are essential for the reconstruction of the lamina propria and epithelialization of the tympanic membrane, whereas collagen deposition and remodeling determine the structural integrity and biomechanical stability of the regenerated tissue. Leukocyte–Platelet Rich Fibrin (L-PRF) is an autologous biomaterial containing platelets, leukocytes, fibrin matrix, and various growth factors that may modulate these biological processes during wound healing. This study aims to examine the biological and molecular basis of L-PRF application in the healing of tympanic membrane perforations, with particular emphasis on the regulation of IL-1β, the expression of FGF, fibroblast and keratinocyte activity, and collagen remodeling. This study employed a focused narrative review approach based on recent scientific literature addressing wound healing mechanisms, cytokine and growth factor regulation, cellular activity in tissue repair, and the application of L-PRF in regenerative medicine and otologic research. The reviewed literature indicates that L-PRF may modulate inflammatory responses through the regulation of IL-1β, enhance FGF expression during the proliferative phase, stimulate fibroblast activity and keratinocyte migration, and support collagen deposition and reorganization through its three-dimensional fibrin scaffold. Nevertheless, integrated experimental evidence specifically investigating traumatic tympanic membrane perforation models remains limited. Biologically, L-PRF demonstrates promising regenerative potential in the healing of tympanic membrane perforations. Further controlled experimental studies are required to comprehensively evaluate the molecular and histological mechanisms involved.