Opening Symposium: Peri-implantitis: A Microbial Disease or Something Else?

The immune system reacts to a foreign material such as titanium and produces bone tissue around the implant to protect nearby tissues. Osseointegration is an immune response. The immune system is likewise behind marginal bone loss (MBL) around oral implants through its control of the osteoblast/osteoclast combined action. The immune system protects the implant against bacterial attacks. Numerous factors related to the implant and the patient as well as to clinical handling combine to cause MBL which is generally an aseptic reaction. If the combined factor attacks are very strong, the immune system may surrender with the result of implant failure. with a combined aseptic and septic attack on osseointegration.

Over the past decade, emerging evidence indicates a strong relationship between prosthetic design and peri-implant tissue health.  An ideal implant position is one of the most critical factors in achieving an acceptable implant restorative design. Malpositioned implants often result in a restorative emergence profile at the implant-abutment junction that can restrict patients' access to adequate oral hygiene. Inadequate cleansability and poor oral hygiene have been reported as precipitating factors to induce peri-implant mucositis and peri-implantitis and are influenced by restorative contours. The implant-abutment connection, restorative material selection, and restoration design are also reported in the literature as potentially affecting peri-implant soft tissue health.

Dental implants replace missing teeth in at least 100 million people, yet over one million implants fail every year due to peri-implantitis, a bacterially induced inflammatory disease. Our ability to treat peri-implantitis is hampered by a paucity of information on host-microbiome interactions that underlie the disease. By characterizing molecular events at the mucosal-microbial interface in the peri-implant crevice, we discovered an active peri-implant microbiome surrounding healthy implants. Microbial genes regulate human genes encoding cell development, metabolism, morphogenesis, adhesion, gap junctions, cell-cell signaling and immuno-inflammatory pathways, suggesting a role for commensals in protecting epithelial integrity. In disease, we discovered that microbial dysbiosis in the peri-implant sulcus promotes abandonment of host-bacterial transactions that dictate health and instead drives a move towards chronic programming of a non-healing wound. 

Implant-associated osteomyelitis is the bane of elective orthopaedic surgeries (i.e. total joint replacement).  Staphylococcus aureus is the primary pathogen, and 50% of cases involve MRSA.  I will present experimental evidence with clinical correlates demonstrating four distinct pathogenic mechanisms: intracellular infection, biofilm on implants and necrotic tissue, staphylococcus abscess communities and colonization of osteocyte lacuno-canalicular network (OLCN).  I will also present pre-clinical and clinical data on the immune proteome against S. aureus, and that both protective antibodies and pathogenic antibodies exist.  Protective antibodies (e.g. anti-glucosaminidase) neutralize critical S. aureus proteins, while pathogenic antibodies (e.g. anti-IsdB) facilitate Trojan horse leukocyte formation, bacteria dissemination from surgical site infection, and septic death.

Based on these basic science discoveries I will present pre-clinical research on bone targeting antibiotics, which overcome the pharmacokinetic and biodistribution limits of standard of care antibiotics, and have potential to kill bacteria within the OLCN of cortical bone.  I will also present pre-clinical data on a passive immunization for MRSA.  As there are many parallels between orthopaedic implant-associated osteomyelitis and peri-implantitis, I will conclude with thoughts on how this new information might be used to prevent and manage oral infections.

The majority of dental scientists and clinicians believe that the primary etiology of dental implant loss is related to oral biofilm. In fact a number of recent publications indicated that this bacterial mass is the sole etiologic factor in the vast majority of cases of peri-implant mucositis and peri-implantitis. However, there is a growing body of evidence that implicates small particles of titanium and zirconium in the etiology of the inflammatory response seen in these cases. This process is termed metallosis. It was first discovered around failing prosthetic knees and shoulders. Emerging evidence has linked these particles to inflammation around dental implants. This lecture will cover the current understanding of this phenomenon and how it relates to dental implant failure as well as appropriate steps to avoid and treat the problem.