Impact of autologous platelet concentrates on the osseointegration of dental implants.

Osseointegration is defined as the direct deposition of bone onto biomaterial devices, most commonly composed from titanium, for the purpose of anchoring dental prostheses. The use of autologous platelet concentrates (APC) has the potential to enhance this process by modifying the interface between the host and the surface of the titanium implant. The rationale is to modify the implant surface and implant-bone interface via "biomimicry," a process whereby the deposition of the host's own proteins and extracellular matrix enhances the biocompatibility of the implant and hence accelerates the osteogenic healing process. This review of the available evidence reporting on the effect of APC on osseointegration explores in vitro laboratory studies of the interaction of APC with different implant surfaces, as well as the in vivo and clinical effects of APC on osseointegration in animal and human studies. The inherent variability associated with using autologous products, namely the unique composition of each individual's blood plasma, as well as the great variety in APC protocols, combination of biomaterials, and clinical/therapeutic application, makes it is difficult to make any firm conclusions about the in vivo and clinical effects of APC on osseointegration. The available evidence suggests that the clinical benefits of adding PRP and the liquid form of L-PRF (liquid fibrinogen) to any implant surface appear to be limited. The application of L-PRF membranes in the osteotomy site, however, may produce positive clinical effects at the early stage of healing (up to 6 weeks), by promoting early implant stability and reducing marginal bone loss, although no positive longer term effects were observed. Careful interpretation and cautious conclusions should be drawn from these findings as there were various limitations in methodology. Future studies should focus on better understanding of the influence of APCs on the biomaterial surface and designing controlled preclinical and clinical studies using standardized APC preparation and application protocols.

Effects of 970 nm diode laser irradiation on morphology, proliferation, and differentiation of gingival mesenchymal stem cells / Efectos de la irradiación con láser de diodo de 970 m sobre la morfología, la proliferación y la diferenciación de las células madre mesenquimales gingivales

Objective: The objective of this study was to investigate the morphology, proliferation, and differentiation of gingival mesenchymal stem cells (GMSCs) irradiated with a 970 nm Diode Laser (LLLT). It is essential to validate the efficacy of treatment, optimize irradiation conditions and guarantee the safety and quality of stem cells for future use in dental applications. Materials and Methods: GMSCs were cultured in standard conditions and irradiated with a Diode laser (970 nm, 0.5W) with an energy density of 9J/cm2. Cell proliferation was assessed with the WST-1 proliferation kit. GMSCs were differentiated into chondrogenic and osteogenic lineages. Cell morphology was performed with Hematoxylin/eosin staining, and quantitative nuclear analysis was done. Cell viability was monitored with trypan blue testing. Results: GMSCs subjected to irradiation demonstrated a significant increase in proliferation at 72 hours compared to the non-irradiated controls (p=0.027). This indicates that the 970 nm diode laser has a stimulatory effect on the proliferation of GMSCs. LLLT-stimulated GMSCs exhibited the ability to differentiate into chondrogenic and osteogenic lineages. A substantial decrease in cell viability was observed 24 hours after irradiation (p=0.024). However, after 48 hours, the cell viability recovered without any significant differences. This indicates that there might be a temporary negative impact on cell viability immediately following irradiation, but the cells were able to recover and regain their viability over time. Conclusions: This study support that irradiation with a 970 nm diode laser could stimulate the proliferation of GMSCs, maintain their ability to differentiate into chondrogenic and osteogenic lineages, and has minimal impact on the mor- phological characteristics of the cells. These results support the potential use of NIR Lasers in combination with GMSCs as a promising strategy for dental treatments.

Objetivo: El objetivo de este estudio fue investigar la morfología, proliferación y diferenciación de las células madre mesenquimatosas (GMSC) irradiadas con un láser de diodo de 970 nm (LLLT). Es fundamental validar la eficacia del tratamiento, optimizar las condiciones de irradiación y garantizar la seguridad y calidad de las células madre para su uso futuro en aplicaciones dentales.Materiales y Métodos: Las GMSC se cultivaron en condiciones estándar y se irradiaron con un láser de diodo (970 nm, 0,5 W) con una densidad de energía de 9 J/cm2. La proliferación celular se evaluó con el kit de proliferación WST-1. Las GMSC se diferenciaron en linajes condrogénicos y osteogénicos. La morfología celular se realizó con tinción de hematoxilina/eosina y se realizó un análisis nuclear cuantitativo. La viabilidad celular se controló con prueba de azul de tripano. Resultados: Las GMSC sometidas a irradiación demostraron un aumento significativo en la proliferación a las 72 horas en comparación con los controles no irradiados (p=0,027). Esto indica que el láser de diodo de 970 nm tiene un efecto estimulante sobre la proliferación de GMSC. Las GMSC estimuladas con LLLT exhibieron la capacidad de diferenciarse en linajes condrogénicos y osteogénicos. Se observó una disminución sustancial de la viabilidad celular 24 horas después de la irradiación (p=0,024). Sin embargo, después de 48 horas, la viabilidad celular se recuperó sin diferencias significativas. Esto indica que podría haber un impacto negativo temporal en la viabilidad de las células inmediatamente después de la irradiación, pero las células pudieron recuperarse y recuperar su viabilidad con el tiempo. Conclusión: En conclusión, este estudio respalda que la irradiación con un láser de diodo de 970 nm podría estimular la proliferación de GMSC, mantener su capacidad para diferenciarse en linajes condrogénicos y osteogénicos y tiene un impacto mínimo en las características morfológicas de las células. Estos resultados respaldan el uso potencial de láseres NIR en combinación con GMSC como una estrategia prometedora para tratamientos dentales.

Smoking habits do not affect biological responses induced by leucocyte and platelet-rich fibrin in periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Leucocyte- and platelet-rich fibrin has been developed to stimulate wound healing response. However, it is currently unknown whether smoking affects the biological responses elicited by leucocyte- and platelet-rich fibrin on periodontal ligament-derived mesenchymal stromal cells. This study analyzes the kinetics of biomolecule release from leucocyte- and platelet-rich fibrin derived from smokers and nonsmokers and their effect on periodontal ligament cell proliferation and migration as essential biological activities during wound healing. METHODS: Biomolecules present in leucocyte- and platelet-rich fibrin exudates and conditioned media collected from smokers and nonsmokers were analyzed by Luminex arrays. Periodontal ligament-derived mesenchymal stromal cell obtained from one nonsmoker were treated with leucocyte- and platelet-rich fibrin exudates or leucocyte- and platelet-rich fibrin conditioned media derived from both smokers and nonsmokers. The parameters evaluated included cell proliferation, determined by Ki67 immunostaining and migration assessed using transwell assays. Also, cells were treated with nicotine in the presence of fetal bovine serum 10% or leucocyte- and platelet-rich fibrin conditioned media. RESULTS: A similar biomolecular profile was detected in leucocyte- and platelet-rich fibrin exudates and leucocyte- and platelet-rich fibrin conditioned media from smokers and nonsmokers, stimulating (periodontal ligament-derived mesenchymal stromal cell) proliferation, and migration to a comparable degree. Nicotine reduced cell proliferation and migration of periodontal cells; however, this effect was recovered in the presence of leucocyte- and platelet-rich fibrin conditioned media. CONCLUSION: Leucocyte- and platelet-rich fibrin derived from smokers could be an autologous source of biomolecules to stimulate cell biological activities involved in wound healing in smokers who have difficulties in ceasing this habit. Clinical trials are required to evaluate the impact of leucocyte- and platelet-rich fibrin on healing responses in smokers.

Interaction between Different Implant Surfaces and Liquid Fibrinogen: A Pilot In Vitro Experiment.

BACKGROUND: Platelet concentrates like leucocyte- and platelet-rich fibrin (L-PRF) have been widely evaluated in different oral surgical procedures to promote the healing process. However, liquid L-PRF products such as liquid fibrinogen have been poorly explored, especially in the biomimetic functionalization of dental implants. The aim of this in vitro study is to evaluate the interaction between 5 different dental implant surfaces and liquid fibrinogen. METHODS: Five commercially available dental implants with different surfaces (Osseospeed™, TiUnite™, SLActive®, Ossean®, and Plenum®) were immersed for 60 minutes in liquid fibrinogen obtained from healthy donors. After this period, the implants were removed and fixed for scanning electron microscopy (SEM). RESULTS: All dental implants were covered by a fibrin mesh. However, noticeable noncontact areas were observed for the Osseospeed™, TiUnite™, and SLActive® surfaces. On the other hand, Ossean® and Plenum® surfaces showed a dense and uniform layer of fibrin covering almost the entire implant surface. The Osseospeed™, TiUnite™, and SLActive® surfaces presented with lower blood cell numbers inside the fibrin mesh compared with the others. Moreover, at higher magnification, thicker fibrin fibers were observed in contact with Ossean® and Plenum® surfaces. The Plenum ®surface showed the thickest fibers which also inserted and interconnect to the microroughness. CONCLUSION: The initial contact between an implant surface and the fibrin network differs significantly among different implant brands. Further studies are necessary to explore the clinical impact of these observations in the osseointegration process of dental implants.

Combining autologous particulate dentin, L-PRF, and fibrinogen to create a matrix for predictable ridge preservation: a pilot clinical study.

OBJECTIVES: The aim of this study was to describe the histological and clinical outcome of "dentin block" (a mixture of autologous particulate dentin, leukocyte- and platelet-rich fibrin (L-PRF), and liquid fibrinogen) in alveolar ridge preservation. MATERIAL AND METHODS: Ten extraction sockets were grafted with "dentin block," a mixture of particulate autologous dentin with chopped leukocyte-platelet-rich fibrin (L-PRF) membranes at a 1:1 ratio, and liquid fibrinogen as a binder. Two grafted sites were followed at 4 and 5 months, and 6 sites at 6 months. Biopsies were taken from the core of the grafted site for histologic and histo-morphometric analysis. RESULTS: All patients completed the study without any adverse event. The vertical and horizontal dimensions of the alveolar ridge were preserved or even increased after 4, 5, or 6 months and remained stable after 6 months of the implant placement. The histological examination revealed a median relative percentage of bone, dentin, and connective tissue of 57.0, 0.9, and 39.3%, respectively. A comparison of samples at different time points (4, 5, and 6 months) showed a progressive increase in the proportion of bone with a decrease in the proportion of dentin. The bone was compact with normal osteocytes and moderate osteoblastic activity. In 4 out of 10 samples, no dentin was observed; in the other samples, it represented 1-5% (with geometric fragments). CONCLUSIONS: Dentin block showed to be a suitable bone substitute in an alveolar ridges preservation model. CLINICAL RELEVANCE: The promising results of dentin block as a bone substitute in alveolar ridge preservation could have an important clinical impact considering this biomaterial brings together the regenerative potential of three autologous products with excellent biological and clinical behavior, low risk of adverse effects, and feasible acquisition.

Association between the use of statins and periodontal status: a review

ABSTRACT: Background: Statins are drugs used for the treatment of dyslipidemia. However, statins have multiple actions, including anti-inflammatory and immunomodulatory effects, as well as the ability to stimulate new bone formation. Such features could be beneficial for periodontal pathology therapy. Methods: A literature review was conducted using filtered electronic databases (Cochrane and Trip) and unfiltered databases (Medline/PubMed, Scielo and Google Scholar). The articles chosen were controlled and randomized clinical trials that performed local delivery of statins to humans and assessed the effects of immunomodulation and bone regeneration on periodontal disease between 2010 and 2017. All of the studies were blind or double-blind and were written in English. Results: The inclusion criteria were applied to a total of 79 identified articles, and 10 studies were ultimately chosen. The results show that an injected dose of statins or the local delivery of atorvastatin (ATV) leads to a significant improvement in clinical and radiographic periodontal parameters. Moreover, rosuvastatin (RSV) induced stronger beneficial effects when administered systemically, whereas ATV and simvastatin (SMV) had better results following topical delivery. Conclusions: Statins can affect periodontal status, increasing the gain in clinical attachment and decreasing gingival bleeding, probing depth and the magnitude of bone defects. For this reason, statins represent an excellent support measure for conventional periodontal therapy. Specifically, positive effects are seen for local delivery of statins as an adjunct treatment to scaling and root planing (SRP) at doses of 1.2 to 2%. Statins could be administered through topical delivery via direct injection in the periodontal pocket or by brushing with medicated dentifrices. More studies with appropriate designs should evaluate the short and long term clinical benefit of statins inpatients with periodontal pathology. These studies should determine the appropriate dose, timing side effects and ideal vehicles for delivery.

An Innovative Regenerative Endodontic Procedure Using Leukocyte and Platelet-rich Fibrin Associated with Apical Surgery: A Case Report.

Regenerative endodontic procedures (REPs) associated with apical surgery could represent an alternative treatment strategy for patients whose teeth present incomplete root formation and extensive apical lesions. Leukocyte platelet-rich fibrin (L-PRF) has potential benefits in REPs; it could promote apical root formation and optimal bone healing. The aim of this case report was to describe innovative regenerative endodontic therapy using L-PRF in the root canal and an extensive apical lesion in an immature tooth with dens invaginatus and asymptomatic apical periodontitis. A healthy 20-year-old woman was referred to the dental clinic of the Universidad de Los Andes, Santiago, Chile, for endodontic treatment in tooth # 22 with incomplete root development and an extensive apical lesion. The diagnosis was asymptomatic apical periodontitis associated with dens invaginatus type II. The patient was treated with an innovative approach using L-PRF in REPs associated with apical surgery. Follow-ups were performed at 6 months and 1 year later. They included periapical radiographs, cone-beam computed tomographic imaging, sensitivity, and vitality tests. The clinical evaluations performed at 6 months and 1 year revealed an absence of symptoms. The radiographic evaluations showed that the apical lesion was resolved. The cone-beam images indicated that the root length increased and the walls had thickened. The sensitivity tests were positive, and the laser Doppler flowmetry showed positive blood flow after 1 year. The success of the results in this case report indicate that L-PRF can be used as a complement in apical surgery and REPs and could provide an innovative alternative treatment strategy for complex clinical cases like these.

Atorvastatin-medicated dentifrice significantly inhibits CD4+ T cell proliferation: in vitro pilot study / Pasta dental medicada con atorvastatina inhibe de forma significativa la proliferación de células T CD4+: un estudio piloto in vitro

Reports indicate that statins (cholesterol-lowering drugs), in addition to lowering cholesterol, have an immunomodulatory effect. This effect may be beneficial for the treatment of several diseases, including periodontal disease. The aim of the present study was to evaluate the immunomodulatory effect of an atorvastatin-medicated dentifrice on CD4+ T cell proliferation. CD4+ T cell proliferation assays and peripheral blood mononuclear cell (PBMC) viability assays were conducted on PBMCs from healthy donors cultured under the following conditions: control, atorvastatin solution, atorvastatin-medicated dentifrice, and dentifrice without atorvastatin at concentrations of 1, 5, 10, 50 and 100 µM. A Generalized Equation Estimation (GEE) model was used to analyze concentration versus proliferation and concentration versus percentage of dead cells within each group evaluated. Atorvastatin-medicated dentifrice (p-value <0.0001) and atorvastatin solution (p-value <0.0001) significantly inhibited CD4+ T cell proliferation in a dose-dependent manner compared with the dentifrice without atorvastatin and control conditions. Only the relationship between atorvastatin solution and percentage of dead cells was significant compared to the other conditions (p-value 0.019). The results revealed that atorvastatin-medicated dentifrice at concentrations of 1 to 100 µM had immunomodulatory effects, inhibiting CD4+ T cell proliferation without affecting PBMC viability. The other components of the dentifrice did not affect CD4+ T cell proliferation or cell viability, indicating its utility as a vehicle to achieve the desired effects of atorvastatin in periodontal tissue. Controlled clinical trials are still needed to evaluate the clinical effects of an atorvastatin-medicated dentifrice on the periodontium.

La literatura indica que las estatinas (medicamentos para bajar el colesterol), además de reducir el colesterol, tienen un efecto inmunomodulador. Este efecto puede ser beneficioso para el tratamiento de varias enfermedades, incluyendo la enfermedad periodontal. El objetivo de este estudio es evaluar el efecto inmunomodulador de una pasta dental medicada con atorvastatina sobre la proliferación celular de linfocitos T CD4+. A partir de células mononucleares de sangre periférica de donantes sanos (PBMC), se realizaron ensayos de proliferación y viabilidad de linfocitos T CD4+ bajo las siguientes condiciones: control, solución de atorvastatina, dentífrico medicado con atorvastatina y dentífrico sin atorvastatina, en concentraciones 1, 5, 10, 50 and 100 µM. Se realizó el análisis estadístico utilizando el modelo Generalized Equation Estimation (GEE) a fin de analizar la concentración versus la proliferación y la concentración versus el porcentaje de muerte celular para cada uno de los grupos. El dentífrico medicado con atorvastatina (valor p <0,0001) y solución de atorvastatina (valor p <0,0001) inhibieron significativamente la proliferación de células T CD4 + de una manera dependiente de la dosis en comparación con el dentífrico sin atorvastatina y condiciones de control. Sólo la relación entre la atorvastatina solución y el porcentaje de células muertas fue significativa en comparación con las otras condiciones (vale-p 0,019). Los resultados revelaron que el dentífrico medicado con atorvastatina en concentraciones de 1 a 100 mM tenía efectos inmunomoduladores, inhibiendo la proliferación de células T CD4 + sin afectar la viabilidad de PBMC. Los otros componentes del dentífrico no afectaron la proliferación de células T CD4 + o la viabilidad celular, indicando su utilidad como vehículo para conseguir los efectos deseados de atorvastatina en el tejido periodontal. Todavía se necesitan ensayos clínicos controlados para evaluar los efectos clínicos de un dentífrico medicado con atorvastatina sobre el periodonto.

Cambios del estado clínico periodontal según consumo sistémico de estatinas / Changes in clinic periodontal status according to systemic statins intake

Objetivos: Describir los cambios del estado clínico periodontal de pacientes según el consumo sistémico de estatinas por indicación del cardiólogo. Material y método Se realizó un estudio descriptivo en el cual se reclutaron pacientes con periodontitis crónica derivados desde cardiología de la Clínica Dávila. Un grupo de ellos iniciaría terapia de estatinas. Se realizaron mediciones clínicas periodontales de profundidad al sondaje (PS), nivel de inserción clínico, índice de sangrado, área de superficie periodontal inflamada, e índice gingival, al inicio (antes de comenzar la terapia de estatinas) y 6 meses después. Los datos fueron analizados utilizando estadística descriptiva. Resultados Diez pacientes participaron del estudio, 5 con indicación de estatinas. El grupo con estatinas en comparación con el grupo sin estatinas presentó una disminución en promedio: de PS (0,4 mm versus 0,13 mm); porcentaje de sitios con PS > 5 mm (4,16 por ciento versus 1,09 por ciento); de nivel de inserción clínico (0,5 mm versus 0,2 mm), índice de sangrado (27,16 por ciento versus 8,8 por ciento) y área de superficie periodontal inflamada (305,68 mm2 versus 121,35). Conclusiones Estos resultados sugieren que pacientes con periodontitis crónica podrían obtener beneficios de la terapia sistémica con estatinas. Se requiere de estudios clínicos con asignación aleatoria y el óptimo tamaño muestral que comprueben el efecto e impacto de las estatinas sobre el estado periodontal.

Objective: To describe changes in periodontal clinical status of patients according to systemic statin use prescribed by a cardiologist. Material and methods A descriptive study was performed on patients with chronic periodontitis referred from the Department of Cardiovascular Diseases of Dávila Clinic. A group of them began statin therapy. Clinical measurements of periodontal probing depth (PD), clinical attachment level, bleeding index, periodontal inflamed surface area, and gingival index, were performed at baseline (before starting statin therapy) and 6 months later. Data were analyzed using descriptive statistics. Results A total of 10 patients participated in the study, and five of them received statin therapy. The statin group compared to the group without statins, showed a mean decrease in: PD (0.4 mm versus 0.13 mm); percentage of PS sites > 5 mm (4.16 percent versus 1.09 percent); clinical attachment level (0.5 mm versus 0.2 mm), bleeding index (27.16 percent versus 8.8 percent), and periodontal inflamed surface area (305.68 versus 121.35 mm2). Conclusions These results suggest that patients with chronic periodontitis may benefit from systemic therapy with statins. Randomized clinical trials with optimal sample size are required to check the effect and impact of statins on the periodontal status.

Short-term effects of 2% atorvastatin dentifrice as an adjunct to periodontal therapy: a randomized double-masked clinical trial.

BACKGROUND: The pleiotropic effects of statins, such as immunomodulation and anti-inflammatory effects, may also improve periodontal conditions. The aim of the present study is to assess the effectiveness of a dentifrice medicated with 2% atorvastatin in improving clinical periodontal parameters as a complement to non-surgical periodontal treatment (NSPT). METHODS: A randomized, double-masked clinical trial was performed with two parallel groups: 1) atorvastatin group (NSPT plus medicated 2% atorvastatin dentifrice) and 2) placebo group (NSPT plus placebo dentifrice). The effectiveness of these treatments was assessed using periodontal measurements obtained at baseline and 1 month later. The measurements were probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival index (GI), and periodontal inflamed surface area (PISA). Multiple linear regression models were used to compare outcome variables after adjusting for sex, diabetes, and tobacco use. RESULTS: A total of 36 individuals participated in this study (atorvastatin group, n = 18; placebo group, n = 18). Both groups showed improvements in periodontal parameters. The atorvastatin group showed a decrease of 297.63 mm(2) in PISA (95% confidence interval = 76.04 to 519.23; P = 0.01), which was significantly greater than the reduction observed in the placebo group. There was also a significantly greater reduction in mean PD, percentage of sites with PD ≥5 mm, mean CAL, percentage of sites with CAL ≥5 mm, BOP, and GI in the atorvastatin group compared with the placebo group. CONCLUSION: NSPT plus 2% atorvastatin medicated dentifrice was more effective in improving clinical periodontal parameters than NSPT plus a placebo dentifrice.