Currently available evidence indicates that people with diabetes present a slower osseointegration process, less favorable dental implant outcomes, and are at increased risk for peri-implantitis- a progressive, destructive, chronic infection of the soft and hard tissues surrounding the dental implant that ultimately may result in implant loss. It is thus expected that, over time - especially in individuals with systemic conditions such as obesity or diabetes (respectively at >35% and >8% of the U.S. adult population) - larger than anticipated implant losses that will require extensive soft and hard tissue reconstruction in a population whose healing ability is uncertain. Preclinical investigation of peri-implant bone healing on systemically compromised subjects have so far been limited small animal models. While insightful, these models present a reduced translational potential due to dental implant size restrictions and the inability to monitor disease over longer periods. Further, large animal models of type 2 diabetes do not follow the natural course of human disease establishment (obesity leading to diabetes) and have been extremely costly and impractical for the study of peri-implantitis. To date there are also no implant studies in a translational large animal model of metabolic syndrome to investigate its effects on peri-implant bone healing and peri-implantitis. This proposal seeks funding to inaugurate a program of preclinical investigation of peri-implant healing and peri-implantitis disease in a highly translational systemically compromised large animal model (Gttingen minipig). Our preliminary studies indicate that a cafeteria diet onsets obesity/metabolic syndrome followed by diabetes induction in the minipig. The overall goal of this project is to characterize/establish the systemically compromised minipig model for oral implantology surgery through the following aims:
Aim #1 : To characterize bone healing around implants in healthy, metabolic syndrome, and diabetic minipigs. We will test the hypothesis that the same mechanism is responsible for impairing the osseointegration process for diabetic and metabolic syndrome animals relative to healthy minipigs.
Aim #2 : To characterize peri-implant disease progression rates around implants with ligature-induced peri-implantitis in healthy, metabolic syndrome, and diabetic minipigs. We will test the hypothesis that the same tissue healing impairment mechanisms will lead to higher peri-implant disease progression rates for diabetic and metabolic syndrome animals relative to healthy minipigs.
This proposal seeks funding to inaugurate a program of preclinical investigation of peri-implant bone healing in infected and non-infected sites in a medically compromised large animal model. This project is the first systematic attempt to establish baseline bone and soft tissue healing and peri-implant disease progress utilizing a highly translational large animal model presenting systemic conditions of significant public health concern. Since obese-diabetic minipigs share substantial similarities with obese-diabetic humans, such as hyperglycemia, hyperlipidemia, insulin resistance, a proinflammatory status, high blood pressure, and atherosclerosis, the potential impact of the project is of broad public health Impact.
|Coelho, Paulo G; Pippenger, Benjamin; Tovar, Nick et al. (2018) Effect of Obesity or Metabolic Syndrome and Diabetes on Osseointegration of Dental Implants in a Miniature Swine Model: A Pilot Study. J Oral Maxillofac Surg 76:1677-1687|