Role of the NF-κβ Signaling Pathway in Oral Surgery: Regulation of Inflammation, Bone Remodeling and Implant Success

Ioannis Nantsios, Philippos Koulouris, Paraskevi Tzortzi, Panagiotis Peitsinis, Panagiotis Kafas, Theodoros Lillis and Nikolaos Dabarakis

Controlled inflammatory responses play a crucial role in soft tissue healing, bone remodeling and the osseointegration of dental implants in oral surgery. There is an intricate relationship between the signaling pathway of Nuclear Factor-kappa B (NF-κβ), which regulates immune responses and cellular fate and what we know of immunology, bone biology and implantology. This review aims to connect the molecular mechanisms of NF-κβ regulation in order to provide an integrated immuno-biological perspective on modern surgery. For the purpose of conducting a thorough literature search, the information was retrieved from PubMed, Scopus and Web of Science databases for peer-reviewed articles which appeared up to 2026. The key words for research were: Canonical and non-canonical NF-κβ pathways, alveolar bone turnover, polarization of macrophages, immunomodulating biomaterials and peri-implant diseases. The findings illustrate that the activation of the canonical NF-κβ pathway, which happens immediately after surgery, is of utmost importance for the recruitment of immune cells, debris elimination and early angiogenesis. The inflammatory process continues and then declines, allowing M2 macrophage polarization and osteoblast differentiation to take place. In this case, the undesired constant regulation of NF-κβ, caused by presence of bacterial biofilms, injuries received during surgery as a result of too intrusive operations and systemic risk factors, leads to chronic inflammation, RANKL-induced activation of osteoclasts and consequently, to the bone loss near the implants. Clinical success is achieved through the use of effective timing of NF-κβ signaling outcomes instead of complete blocking of signaling pathways. Different methods are used for the delivery of information in order to transform the inflammatory response into stimulation processes associated with the generation of bone tissue and longevity of the implants.

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