The junctional epithelium is located at a strategically important interface between the gingival sulcus, populated with bacteria, and the periodontal soft and mineralized connective tissues that need protection from becoming exposed to bacteria and their products. Its unique structural and functional adaptation enables the junctional epithelium to control the constant microbiological challenge. The antimicrobial defense mechanisms of the junctional epithelium, however, do not preclude the development of gingival and periodontal lesions. The conversion of the junctional to pocket epithelium, which is regarded as a hallmark in disease initiation, has been the focus of intense research in recent years. Research has shown that the junctional epithelial cells may play a much more active role in the innate defense mechanisms than previously assumed. They synthesize a variety of molecules directly involved in the combat against bacteria and their products. In addition, they express molecules that mediate the migration of polymorphonuclear leukocytes toward the bottom of the gingival sulcus. Periodontopathogens—such as Actinobacillus actinomycetemcomitans or, in particular, Porphyromonas gingivalis—have developed sophisticated methods to perturb the structural and functional integrity of the junctional epithelium. Research has focused on the direct effects of gingipains, cysteine proteinases produced by Porphyromonas gingivalis, on junctional epithelial cells. These virulence factors may specifically degrade components of the cell-to-cell contacts. This review will focus on the unique structural organization of the junctional epithelium, on the nature and functions of the various molecules expressed by its cells, and on how gingipains may attenuate the junctional epithelium’s structural and functional integrity.

Multinucleated giant cells (MNGCs) are a special class of giant cell formed by the fusion of monocytes/macrophages abundantly found in human tissues. While historically their role around certain classes of biomaterials have been directly linked to a foreign body reaction leading to material rejection, recent accumulating evidence has put into question their role around certain classes of bone biomaterials. It was once thought that specifically in bone tissues, all giant cells were considered osteoclasts characterized by their ability to resorb and replace bone grafts with newly formed native bone. More recently, however, a special subclass of bone biomaterials has been found bordered by large MNGCs virtually incapable of resorbing bone substitutes even years after their implantation yet surrounded by stable bone. Interestingly, research from the field of cardiovascular disease has further shown how a shift in macrophage polarization from M1 “tissue-inflammatory” macrophages toward M2 “wound-healing” macrophages in atherosclerotic plaque may lead to MNGC formation and ectopic calcification of arteries. Despite the growing observation that MNGC formation occurs around certain bone biomaterials, their role in these tissues remains extremely poorly understood and characterized. In summary, four central aspects of this review are discussed with a focus on (1) the role of MNGCs in bone/tissue biology, and their ability to induce vascularization/new bone formation, their role around, (2) bone substitutes for bone augmentation, (3) dental implants, as well as (4) during peri-implant infection. The authors express the necessity to no longer refer to MNGCs as “good” or “bad” cells, but instead point toward the necessity to more specifically characterize them scientifically and appropriately as M1-MNGC and M2-MNGC accordingly. Future research investigating the factors influencing their polarization as a “center of control” is also likely to act as a key factor in the progression/resolution of various diseases.