Repurposing Metformin for periodontal disease management as a form of oral-systemic preventive medicine.

BACKGROUND: Despite the improvements in treatment over the last decades, periodontal disease (PD) affects millions of people around the world and the only treatment available is based on controlling microbial load. Diabetes is known to increase the risk of PD establishment and progression, and recently, glucose metabolism modulation by pharmaceutical or dietarian means has been emphasised as a significant modulator of non-communicable disease development. METHODS: The impact of pharmaceutically controlling glucose metabolism in non-diabetic animals and humans (REBEC, UTN code: U1111-1276-1942) was investigated by repurposing Metformin, as a mean to manage periodontal disease and its associated systemic risk factors. RESULTS: We found that glucose metabolism control via use of Metformin aimed at PD management resulted in significant prevention of bone loss during induced periodontal disease and age-related bone loss in vivo. Metformin also influenced the bacterial species present in the oral environment and impacted the metabolic epithelial and stromal responses to bacterial dysbiosis at a single cell level. Systemically, Metformin controlled blood glucose levels and age-related weight gain when used long-term. Translationally, our pilot randomized control trial indicated that systemic Metformin was safe to use in non-diabetic patients and affected the periodontal tissues. During the medication window, patients showed stable levels of systemic blood glucose, lower circulating hsCRP and lower insulin levels after periodontal treatment when compared to placebo. Finally, patients treated with Metformin had improved periodontal parameters when compared to placebo treated patients. CONCLUSION: This is the first study to demonstrate that systemic interventions using Metformin in non-diabetic individuals aimed at PD prevention have oral-systemic effects constituting a possible novel form of preventive medicine for oral-systemic disease management.

Evaluation of Bone Regeneration in Rat Calvaria Using Bone Autologous Micrografts and Xenografts: Histological and Histomorphometric Analysis.

The aim of this study was to investigate the effect of the use of autologous micrografts obtained by the Rigenera® Micrografting Technology and xenograft on critical size defects created in the calvaria of rats. Forty-eight rats were randomly divided into four groups for each of the two evaluation times (15 and 30 days) (n = 6). After general anesthesia, a 5-mm diameter bone defect was created in the calvaria of each animal. Each defect was filled with the following materials: blood clot, autologous bone graft, xenograft, and xenograft associated with autologous micrografts. Histomorphometric and histological analysis showed that the group that have received the Rigenera® processed autologous micrografts combined with the xenograft and the group that received autologous bone graft resulted in greater bone formation in both time points when compared with the use of the xenograft alone and blood clot.

Autologous Periosteum-Derived Micrografts and PLGA/HA Enhance the Bone Formation in Sinus Lift Augmentation.

Sinus lift augmentation is a procedure required for the placement of a dental implant, whose success can be limited by the quantity or quality of available bone. To this purpose, the first aim of the current study was to evaluate the ability of autologous periosteum-derived micrografts and Poly(lactic-co-glycolic acid) (PLGA) supplemented with hydroxyl apatite (HA) to induce bone augmentation in the sinus lift procedure. Secondly, we compared the micrograft's behavior with respect to biomaterial alone, including Bio-Oss® and PLGA/HA, commercially named Alos. Sinus lift procedure was performed on 24 patients who required dental implants and who, according to the study design and procedure performed, were divided into three groups: group A (Alos + periosteum-derived micrografts); group B (Alos alone); and group C (Bio-Oss® alone). Briefly, in group A, a small piece of periosteum was collected from each patient and mechanically disaggregated by Rigenera® protocol using the Rigeneracons medical device. This protocol allowed for the obtainment of autologous micrografts, which in turn were used to soak the Alos scaffold. At 6 months after the sinus lift procedure and before the installation of dental implants, histological and radiographic evaluations in all three groups were performed. In group A, where sinus lift augmentation was performed using periosteum-derived micrografts and Alos, the bone regeneration was much faster than in the control groups where it was performed with Alos or Bio-Oss® alone (groups B and C, respectively). In addition, the radiographic evaluation in the patients of group A showed a radio-opacity after 4 months, while after 6 months, the prosthetic rehabilitation was improved and was maintained after 2 years post-surgery. In summary, we report on the efficacy of periosteum-derived micrografts and Alos to augment sinus lift in patients requiring dental implants. This efficacy is supported by an increased percentage of vital mineralized tisssue in the group treated with both periosteum-derived micrografts and Alos, with respect to the control group of Alos or Bio-Oss® alone, as confirmed by histological analysis and radiographic evaluations at 6 months from treatment.

Application of subepithelial connective tissue graft with or without enamel matrix derivative for root coverage: a split-mouth randomized study.

The primary aim of this randomized clinical investigation was to evaluate gingival recession defects treated by a coronally advanced flap and sub-epithelial connective tissue graft (SCTG) with or without enamel matrix derivative (EMD). Twelve patients with Miller's class III buccal recession defects of ≥2.0 mm in similar contra lateral sites were included in this split-mouth randomized study. Test sites were treated with SCTG plus EMD while control sites received SCTG only. At baseline, 6 months and 12 months, clinical parameters such as recession level (RL), probing depth (PD), clinical attachment level (CAL), and apico-cervical width of keratinized tissue (KT) were determined. A P value <0.05 was considered significant. Compared to the baseline and based on paired t tests, both groups had significant improvement in all the clinical parameters. However, the test group showed better results in RL (P = 0.046) and CAL (P = 0.023) at 6 months. At 12 months, the test group demonstrated better results in RL (P = 0.01), PD (P = 0.017) and CAL (P = 0.001). Only the KT results were not significantly different between groups at both 6 and 12 months (P = 0.708) and (P = 0.570), respectively. The present study demonstrated the benefit of adding EMD to SCTG for root coverage in Miller's class III buccal gingival recession defects after 12 months. (J Oral Sci 52, 463-471, 2010).