Abstract This study investigated the influence of resveratrol on peri-implant repair and its effects on bone-related markers in ovariectomy-induced osteoporosis in rats. Animals were divided into: OVX+PLAC (n = 10): ovariectomized animals treated with placebo; OVX+RESV (n = 10): OVX treated with resveratrol; OVX+PLAC+ZOL (n = 10): OVX treated with PLAC and zoledronate; OVX+RESV+ZOL (n = 10): OVX treated with RESV and ZOL; and SHOVX+PLAC (n = 10): sham ovariectomy treated with PLAC. RESV and PLAC were administrated after ovariectomy and ZOL after six weeks after OVX, until the end of experiment. One implant was inserted in each tibiae of animals 18 weeks after ovariectomy. After 4 weeks, one implant was removed for counter-torque, and peri-implant tissue was collected for mRNA quantification of several osteogenic markers by PCR. The other tibia was submitted to micro-computed tomography analysis. Reduced counter-torque values, bone-implant contact (BIC) and bone volume fraction (BV/TV), and higher bone porosity (BP) were detected in OVX+PLAC group when compared to SHOVX+PLAC (p < 0.05). OVX+RESV rats presented lower BIC, BV/TV, and trabecular number (Tb.N), and augmented BP and trabecular spacing (Tb.Sp) when compared to SHOVX+PLAC (p < 0.05). Higher Tb.N and connectivity density (Conn.Dn) and reduced Tb.Sp were observed in OVX rats treated with ZOL, independently of RESV, when compared to OVX+PLAC and OVX+RESV groups (p < 0.05), whereas the combination ZOL+RESV promoted lower BP when compared to OVT+PLAC and OVX+RESV (p < 0.05). Gene expression was not influenced by RESV (p > 0.05), whereas ZOL promoted up-regulation of BMP-2 (p<0.05). RESV did not improve peri-implant bone repair in rats with ovariectomy-induced osteoporosis. periimplant peri bonerelated related ovariectomyinduced induced into OVXPLAC n 10 10) placebo OVXRESV OVXPLACZOL zoledronate OVXRESVZOL SHOVXPLAC SHOVX experiment 1 countertorque, countertorque counter torque, torque PCR microcomputed micro computed analysis values boneimplant BIC (BIC BVTV BV/TV , BV TV (BV/TV) (BP p 0.05. 005 0.05 . 0 05 0.05) Tb.N, TbN Tb N (Tb.N) TbSp Sp (Tb.Sp Conn.Dn ConnDn Conn Dn (Conn.Dn 0.05, ZOLRESV OVTPLAC OVT upregulation up regulation BMP2 BMP 2 BMP- p<0.05. p005 p<0.05 (p<0.05) (BV/TV 00 0.0 (Tb.N p00 p<0.0 (p<0.05 0. p0 p<0. (p<0.0 p<0 (p<0. p< (p<0 (p<

Abstract This study investigated the impact of a modified implant macrogeometry on peri-implant healing and its effect on bone-related molecules in rats. Eighteen rats received one implant in each tibia: the control group received implants with conventional macrogeometry and the test group received implants with modified macrogeometry. After 30 days, the implants were removed for biomechanical analysis and the bone tissue around them was collected for quantifying gene expression of OPN, Runx2, β-catenin, BMP-2, Dkk1, and RANKL/OPG. Calcein and tetracycline fluorescent markers were used for analyzing newly formed bone at undecalcified sections of the tibial implants. These fluorescent markers showed continuous bone formation at cortical bone width and sparse new bone formed along the medullary implant surface in both groups. However, higher counter-torque values and upregulation of OPN expression were achieved by test implants when compared to controls. The modified macrogeometry of implants optimized peri-implant healing, favoring the modulation of OPN expression in the osseous tissue around the implants. periimplant peri bonerelated related tibia 3 days Runx2 Runx βcatenin, βcatenin β catenin, catenin β-catenin BMP2, BMP2 BMP 2, 2 BMP-2 Dkk1 Dkk RANKLOPG RANKL OPG RANKL/OPG groups However countertorque counter torque controls BMP-

Abstract Although dental implants and bone regenerative procedures are important approaches for the reestablishment of esthetics and function in young patients with a history of generalized aggressive periodontitis (GAP), no predictable outcomes have been reported, and the host osteo-immunoinflammatory response may play a relevant role in this context. In view of the lack of molecular investigations into the bone tissue condition of young patients with periodontitis, the aim of this study was to evaluate the gene expression of bone-related factors in this population. Bone biopsies were obtained from the posterior mandible in 16 individuals previously diagnosed with GAP and on periodontal support therapy and from 17 periodontally healthy (PH) patients. The gene expression of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, receptor activator of the NF-κB ligand (RANKL), osteoprotegerin (OPG), osteocalcin (OC), bone sialoprotein (BSP), and type I collagen (COL-I), important biomarkers of bone turnover, was evaluated by qRT-PCR. Lower TGF-β and OPG mRNA levels were observed in GAP patients compared to PH individuals (p ≤ 0.05). There were no between-group differences in levels of TNF-α, BSP, RANKL, OC, or COL-I mRNA (p>0.05). In young adults, a history of periodontal disease can negatively modulate the gene expression of important bone-related factors in alveolar bone tissue. These molecular outcomes may contribute to the future development of therapeutic approaches to benefit bone healing in young patients with history of periodontitis via modulation of osteo-immuno-inflammatory biomarkers.

Abstract Considering the absence of predictable and effective therapeutic interventions for the treatment of peri-implantitis, scientific evidence concerning the host response profile around dental implants could be important for providing in the future a wider preventive and/or therapeutic window for this peri-implant lesion, indicating biomarkers that provide quantifiable measure of response to peri-implant therapy. Moreover, a better knowledge of pattern of host osteo-immunoinflammatory modulation in the presence of peri-implantitis could either benefit the early diagnostic of the disease or to cooperate to prognostic information related to the status of the peri-implant breakdown. Finally, new evidences concerning the host profile of modulators of inflammation and of osseous tissue metabolism around dental implants could explain the individual susceptibility for developing peri-implant lesions, identifying individuals or sites with increased risk for peri-implantitis. The focus of this chapter was, based on a systematically searched and critically reviewed literature, summarizing the existing knowledge in the scientific research concerning the host osteo-immunoinflammatory response to the microbiological challenge related to periimplantitis.

RESUMO A engenharia de tecidos é um campo contemporâneo da ciência, que visa criar condições baseadas em princípios de biologia celular e molecular, bioengenharia e biomateriais para regenerar tecidos. As células tronco mesenquimais apresentam altas taxas de proliferação e são capazes de se diferenciar, sob certas condições, em multi-linhagens, sugerindo que elas têm grande potencial para atuar no campo da regeneração. As células tronco derivadas de tecidos dentais são uma fonte alternativa adequada de células mesenquimais uma vez que são de fácil acesso e têm baixa morbidade para o doador. Estudos demonstraram que elas já foram isoladas e caracterizadas a partir de diversos tecidos tais como polpa dentária, dentes decíduos esfoliados, ligamento periodontal, gengiva, folículo dental e papila apical. Entretanto, os estudos demonstram que há heterogeneidade entre essas populações e não existe um método padrão para selecionar as células-tronco dentais mais apropriadas para procedimentos regenerativos. O objetivo desta revisão é apresentar o conhecimento atual dos vários tipos de células-tronco derivadas de dentes e discutir as novas perspectivas para seu uso na engenharia de tecidos periodontais.

ABSTRACT Tissue engineering is a contemporary field of science, which aims to create conditions based on principles of cell and molecular biology, bioengineering and biomaterials to regenerate tissues. Mesenchymal stem cells present high proliferation rates and are able to differentiate into multilineages under certain conditions, suggesting that they have great potential to act in regeneration field. Tooth derived stem cells are a suitable alternative source of mesenchymal cells once they are easily accessible and have poor morbidity to the donor. Studies showed that they have been isolated and characterized from diverse tissues such as dental pulp, exfoliated deciduous teeth, periodontal ligament, gingiva, dental follicle and apical papilla. However studies show that there is heterogeneity among these populations and there is no standard method to select the most appropriate tooth derived stem cells for regenerative procedures. The aim of this review is to present the current perspective of the multiple types of tooth-derived stem cells and to discuss the basis for their use in periodontal tissue engineering.

ABSTRACT The use of natural substances and micronutritional approaches has been suggested as a therapeutic alternative to benefit the bone healing associated with no side effects. Nevertheless, the influence of micronutritional interventions with therapeutic proprieties on the bone repair has yet to be intensely evaluated, and no evidence is available exploring the impact of micronutrient supplementation on the peri-implant bone healing. Objective This study investigated the effect of micronutrients supplementation on the bone repair around implants. Material and Methods One screw-shaped titanium implant was inserted in each tibia of each rat, which were assigned to: daily administration, for 30 d, of the placebo solution (Placebo group-n:18) or micronutrients supplementation (Micronutrients group-n:18), based on calcium, magnesium, zinc, and vitamin D3 intake. After, the animals were sacrificed. One of the implants was removed by applying a counter-torque force to evaluate the force to rupture the bone-implant interface. The other implant was evaluated by microcomputed tomography (CT) examination to determine the bone-to-implant contact (BIC) and the bone volume (BV/TV). Results No statistically significant differences were observed between the groups for both counter-torque values and microCT parameters (p>0.05). Conclusion Within the limits of this study, micronutrients supplementation did not provide additional benefits to the bone healing around dental implants.

Abstract The objective of this study was to investigate the antibacterial effect of resveratrol against putative periodontal pathogens during the progression of experimental periodontitis in rats. Periodontitis was induced in rats in one of the first molars chosen to receive a ligature. Animals were assigned to one of two groups: daily administration of the placebo solution (control group, n = 12) or 10 mg/Kg of resveratrol (RESV group, n = 12). The therapies were administered systemically for 30 days, for 19 days before periodontitis induction and then for another 11 days. Then, the presence and concentrations of Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans in the cotton ligatures collected from the first molars were evaluated using real-time PCR. Inter-group comparisons of the microbiological outcomes revealed that no differences were detected for P. gingivalis, T. forsythia and A. actinomycetemcomitans levels (p > 0.05). Continuous use of resveratrol did not promote additional benefits in microbiological outcomes during experimental periodontitis in rats.

OBJECTIVE: This study was designed to evaluate the potential adjunctive benefits of platelet-rich plasma (PRP) when used with guided-tissue regeneration (GTR) and bioactive glass (BG) in the treatment of Class II furcation lesions. MATERIAL AND METHODS: Bilateral Class II furcation lesions were surgically created and allowed to become chronic in the mandibular third premolars of 9 dogs. The defects were randomly assigned to: A) GTR+BG and B) GTR+BG+PRP. Similar defects were created in the maxillary third premolars and received the same treatments after 45 days. Dogs were sacrificed 90 days after the first treatment. The histometric parameters evaluated were: connective tissue adaptation, new cementum, new bone, mineralized bone area, non-mineralized bone area, and residual BG particle area. RESULTS: Data analysis showed a superior length of new cementum and a greater mineralized bone area for group B in both periods (p<0.05). The non-mineralized bone area was greater in the control group (p<0.05) in both periods. CONCLUSION: Within the limits of this study, it can be concluded that the use of PRP in the treatment of Class II furcation defects may enhance the amount of new cementum and provide a more mineralized bone in a shorter period of time.

OBJECTIVE: This study was designed to evaluate, histomorphometrically, the association of platelet-rich plasma (PRP) and bioactive glass (BG) in the treatment of periodontal intrabony defects. MATERIAL AND METHODS: Nine mongrel dogs were included in the study. Three-wall intrabony defects were surgically created at the mesial and distal aspect of first mandibular molar and exposed to plaque accumulation for 1 month. The defects were randomly assigned to the groups: control, BG, PRP, PRP+BG. Dogs were sacrificed 90 days after the surgeries. The histometric parameters evaluated were: length of sulcular and junctional epithelium, connective tissue adaptation, new cementum, new bone, defect extension and area of new bone filling the defect. RESULTS: A superior area of new bone was observed in PRP+BG and BG (13.80±2.32 mm² and 15.63±2.64 mm², respectively) when compared to the other groups (8.19±1.46 mm² and 8.81±1.47 mm² for control and PRP, respectively). No statistically significant differences were observed in the remaining parameters. CONCLUSIONS: Within the limits of this study, it may be concluded that PRP failed to provide statistically significant improvements in the histometric parameters.

O objetivo do presente estudo foi avaliar histometricamente a influência da nicotina sobre a regeneração óssea de defeitos criados cirurgicamente em rebordos alveolares edêntulos de cães. Defeitos ósseos foram criados cirurgicamente em um dos lados da mandíbula de dezesseis cães e foram deixados para que curassem espontanea-mente. Os animais foram aleatoriamente designados para um dos seguintes grupos: Grupo 1 - controle (n = 8) e Grupo 2 - administração subcutânea de nicotina (2 mg/kg) duas vezes ao dia durante 4 meses (n = 8). Os animais foram sacrificados, e secções semi-seriadas descalcificadas, obtidas. Os parâmetros histométricos avaliados foram altura, largura, área e densidade do tecido ósseo neoformado. A análise intergrupos (Mann-Whitney "rank sum test") demonstrou que a administração de nicotina não influenciou altura, largura e área de tecido ósseo neoformado (p > 0,05). Entretanto, a administração de nicotina influenciou significativamente a densidade do tecido ósseo neoformado (p < 0,001). Dentro dos limites do presente estudo, pode-se concluir que a nicotina pode afetar, mas não impedir a regeneração de defeitos ósseos criados cirurgicamente em mandíbulas edêntulas de cães.

The objective of this study was to investigate the histometric impact of nicotine on bone regeneration of surgically created alveolar ridge defects in dogs. Sixteen mongrel dogs were used. One defect was surgically created unilaterally in the mandible, and left to heal spontaneously. The animals were randomly assigned to one of the following groups: Group 1 - control (n = 8) and Group 2 - subcutaneous nicotine administration (2 mg/kg) twice a day (n = 8). After 4 months, the animals were sacrificed and the specimens routinely processed for semi-serial decalcified sections. Bone height (BH), bone width (BW), bone density (BD), and bone area (BA) of the newly-formed bone were evaluated. Intergroup analysis (Mann-Whitney rank sum test) showed that regardless of the presence of nicotine, no significant differences were observed regarding bone width (BW), bone area (BA) and bone height (BH) (p > 0.05). On the other hand, it was demonstrated that nicotine administration significantly influenced the proportion of mineralized tissue within the limits of the newly-formed bone (BD) (p < 0.001). Within the limits of the present study, it can be concluded that nicotine might affect but not prevent bone healing in defects left to heal spontaneously.