Melatonin: a review of its potential functions and effects on dental diseases

Melatonin is a hormone synthesised and secreted by the pineal gland and other organs. Its secretion, controlled by an endogenous circadian cycle, has been proven to exert immunological, anti-oxidant, and anti-inflammatory effects that can be beneficial in the treatment of certain dental diseases. This article is aimed at carrying out a review of the literature published about the use of melatonin in the dental field and summarising its potential effects. In this review article, an extensive search in different databases of scientific journals was performed with the objective of summarising all of the information published on melatonin use in dental diseases, focussing on periodontal diseases and dental implantology. Melatonin released in a natural way into the saliva, or added as an external treatment, may have important implications for dental disorders, such as periodontal disease, as well as in the osseointegration of dental implants, due to its anti-inflammatory and osseoconductive effects. Melatonin has demonstrated to have beneficial effects on dental pathologies, although further research is needed to understand the exact mechanisms of this moleculeS

Regeneration of keratinized tissue around teeth and implants following coronal repositioning of alveolar mucosa with and without a connective tissue graft: an experimental study in dogs

Aim: To compare clinical and histological keratinized tissue formation around teeth and implants following coronal repositioning of alveolar mucosa with or without a connective tissue graft (CTG).Materials and Methods: In nine beagle dogs, the third and fourth premolars (P3 and P4) were extracted from one side of the maxilla. Three months after the tooth extraction, a full-thickness buccal flap was raised and two implants were placed in those healed areas. On the contra-lateral side, a buccal flap was also raised at the P3 and P4 areas. Before suturing, the dogs were randomly assigned to three study groups (control, non-keratinized tissue [NKT], and non-keratinized tissue CTG [NKT-CTG]). In the control group, the buccal flaps were re-positioned around the teeth (P3 and P4) on one side, and implants on the other side, presenting an adequate band of keratinized tissue (KT). For the NKT and NKT-CTG groups, this buccal KT was then excised. In the NKT group, the buccal flap without KT (alveolar mucosa) was re-positioned around the teeth and implants. In the NKT-CTG group, a CTG taken from the excised KT was sutured to the buccal alveolar mucosa and then both were re-positioned around the teeth and implants. The clinical height of the KT was measured at baseline and at 1, 2, and 3 months of healing. The animals were sacrificed at 3 months, at which point the KT height was measured histologically. Results: The control group presented normal healing with a band of KT surrounding the teeth and implants. In the NKT and NKT-CTG groups, a new KT band approximately 2 mm in height (measured clinically and histologically) spontaneously formed around all teeth, regardless of whether a CTG had been placed. In the NKT implant group, no new KT was observed (clinically or histologically). Around the implants in the NKT-CTG group, a small amount of KT was formed in just two of the six implants.Conclusions: After surgical excision of KT, spontaneous KT is formed around teeth but not around implants, regardless of the placement of a CTGS

Comparison of various SYSADOA for the osteoarthritis treatment: an experimental study in rabbits

Background: Osteoarthritis is thought to be the most prevalent chronic and disabling joint disease in animals and humans and its treatment is a major orthopaedic challenge because there is no ideal drug treatment to preserve joint structure and function, as well as to ameliorate the symptomatology of the disease. The aim of the present study was to assess, using histology, histomorphometry and micro-CT, the effects of the treatment with several drugs of the SYSADOA group and a bisphosphonate in a model of early osteoarthritis, comparing all the results obtained. Methods: Osteoarthritis was surgically induced by anterior cruciate ligament transection and partial meniscectomy on one knee of 56 rabbits; treatment was started three weeks after surgery and lasted 8 weeks; at the end of this period, the animals were sacrificed. Animals were divided into seven groups (8 animals each), one for each regimen of treatment (glucosamine sulfate, chondroitin sulfate, hyaluronic acid, diacerein, risedronate and a combination of risedronate and glucosamine) and one for the control (placebo-treated) group. Following sacrifice, femoral osteochondral cylinders and synovial membrane samples were obtained for their evaluation by qualitative and quantitative histology and micro-CT. Results: The model induced osteoarthritic changes in the knee joints and none of the treatments showed a significantly better efficacy over the others. Regarding cartilage thickness and volume, all the treatments achieved scores halfway between control groups, without statistical differences. Regarding the synovial membrane, diacerein and risedronate showed the best anti-inflammatory profile, whereas glucosamine and chondroitin did not present any effect standing the hyaluronic acid results between the others. Regarding the subchondral bone, there were no differences in thickness or volume, but risedronate, diacerein and hyaluronic acid seemed to have considerably modified the orientation of the trabecular lattice. Conclusions: Out of the different drugs evaluated in the study for OA treatment, diacerein and risedronate showed, in all the parameters measured, a better profile of effectiveness; hyaluronic acid ameliorated cartilage swelling and promoted bone formation, but with a poor synovial effect; and finally, chondroitin and glucosamine sulfate prevented cartilage swelling in a similar way to the others, but had no effect on cartilage surface, synovial membrane or subchondral bone.The authors thank the Dirección Xeral de I + D + i, Consellería de Economía e Industria, Xunta de Galicia for funding this work through research project 09CSA008E, cofinanced by European regional and social funds (FEDER and FSE) from European Union and by a grant of Fundación Salud 2000S

Effects of glucosamine and risedronate alone or in combination in an experimental rabbit model of osteoarthritis

Background: The osteoarthritis (OA) treatment in humans and in animals is a major orthopaedic challenge because there is not an ideal drug for preserving the joint structure and function. The aim of this study was to assess the effects of the treatment with oral glucosamine and risedronate alone or in combination on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of OA. Osteoarthritis was surgically induced on one knee of 32 New Zealand White rabbits using the contralateral as healthy controls. Three weeks later treatments were started and lasted 8 weeks. Animal were divided in four groups of oral treatment: the first group received only saline, the second 21.5 mg/kg/day of glucosamine sulfate, the third 0.07 mg/kg/day of risedronate; and the fourth group both drugs simultaneously at the same dosages. Following sacrifice femurs were removed and osteochondral cylinders and synovial membrane were obtained for its histological and micro-CT evaluation. Results: Sample analysis revealed that the model induced osteoarthritic changes in operated knees. OA placebo group showed a significant increase in cartilage thickness respect to the control and inflammatory changes in synovial membrane; whereas subchondral bone structure and volumetric bone mineral density remained unchanged. All the treated animals showed an improvement of the cartilage swelling independent of the drug used. Treatment with glucosamine alone seemed to have no effect in the progression of cartilage pathology while risedronate treatment had better results in superficial fibrillation and in resolving the inflammatory changes of the tissues, as well as modifying the orientation of trabecular lattice. The combination of both compounds seemed to have additive effects showing better results than those treated with only one drug. Conclusions: The results of this animal study suggested that glucosamine sulfate and risedronate treatment alone or in combination may be able to stop cartilage swelling. The risedronate treatment could partially stop the fibrillation and the inflammation of synovial membrane as well as modify the orientation of trabeculae in healthy and in osteoarthritic kneesThe authors thank the Dirección Xeral de I + D + i, Consellería de Economía e Industria, Xunta de Galicia for funding this work through research project 09CSA008E, cofinanced by European regional and social funds (FEDER and FSE) from European Union and by a grant of Fundación Salud 2000S

Histomorphometric Quantitative Evaluation of Long-Term Risedronate Use in a Knee Osteoarthritis Rabbit Model

Osteoarthritis (OA) treatment is a major orthopedic challenge given that there is no ideal drug capable to reverse or stop the progression of the OA. In that regard, bisphosphonates have been proposed as potential disease-modifying drugs due to their possible chondroprotective effect related to obtaining a greater subchondral bone quality. However, their effectiveness in OA is still controversial and additionally, there is little evidence focused on their long-term effect in preclinical studies. The aim of this study was to evaluate the risedronate quantitative effect on articular and subchondral periarticular bone by histomorphometry, in an experimental rabbit model in an advanced stage of OA. Twenty-four adult New Zealand rabbits were included in the study. OA was surgically induced in one randomly chosen knee, using the contralateral as healthy control. Animals were divided into three groups (n = 8): placebo control group, sham surgery group and risedronate-treated group. After 24 weeks of treatment, cartilage and subchondral femorotibial pathology was evaluated by micro-computed tomography (micro-CT) and undecalcified histology. The research results demonstrated that the experimental animal model induced osteoarthritic changes in the operated joints, showing an increased cartilage thickness and fibrillation associated with underlying subchondral bone thinning and decreased trabecular bone quality. These changes were especially highlighted in the medial tibial compartments as a possible response to surgical instability. Regarding the trabecular analysis, significant correlations were found between 2D histomorphometry and 3D imaging micro-CT for the trabecular bone volume, trabecular separation, and the trabecular number. However, these associations were not strongly correlated, obtaining more precise measurements in the micro-CT analysis. Concerning the long-term risedronate treatment, it did not seem to have the capacity to reduce the osteoarthritic hypertrophic cartilage response and failed to diminish the superficial cartilage damage or prevent the trabecular bone loss. This study provides novel information about the quantitative effect of long-term risedronate use on synovial joint tissuesThis study was self-funded by the Laboratory of bone-material analysis, Department of Anatomy, Animal Production and Veterinary Clinical Sciences, USC-Lugo, Spain and a grant of Xunta de Galicia (GRC ED431C 2017/37)S

Comparison between Sandblasted Acid-Etched and Oxidized Titanium Dental Implants: In Vivo Study

The surface modifications of titanium dental implants play important roles in the enhancement of osseointegration. The objective of the present study was to test two different implant surface treatments on a rabbit model to investigate the osseointegration. The tested surfaces were: a) acid-etched surface with sandblasting treatment (SA) and b) an oxidized implant surface (OS). The roughness was measured by an interferometeric microscope with white light and the residual stress of the surfaces was measured with X-ray residual stress Bragg–Bentano diffraction. Six New Zealand white rabbits were used for the in vivo study. Implants with the two different surfaces (SA and OS) were inserted in the femoral bone. After 12 weeks of implantation, histological and histomorphometric analyses of the blocks containing the implants and the surrounding bone were performed. All the implants were correctly implanted and no signs of infection were observed. SA and OS surfaces were both surrounded by newly formed trabeculae. Histomorphometric analysis revealed that the bone–implant contact % (BIC) was higher around the SA implants (53.49 ± 8.46) than around the OS implants (50.94 ± 16.42), although there were no significant statistical differences among them. Both implant surfaces (SA and OS) demonstrated a good bone response with significant amounts of newly formed bone along the implant surface after 12 weeks of implantation. These results confirmed the importance of the topography and physico–chemical properties of dental implants in the osseointegration.The authors are grateful to the Spanish Government and European Union FEDER by the concession of the project RTI2018-098075-B-C22S

Influence on Bone-to-Implant Contact of Non-Thermal Low-Pressure Argon Plasma: An Experimental Study in Rats

Roughness characteristics play an essential role in osseointegration. However, there is a concern about the susceptibility of those surfaces to bacterial colonization. New techniques for cleaning and surface treatment have appeared that could favor osseointegration without the need to create surfaces as rough. Such is the case of non-thermal low-pressure argon plasma (NTLP-ArP). One hundred and forty-four implants were placed in the tibiae of 36 Sprague Dawley rats, distributed in four experimental groups: I: mechanized surface; II: mechanized surface treated with NTLP-ArP, III: resorbable blast media (RBM) surface; and IV: RBM surface treated with (NTLP-ArP). Bone-to-implant contact (BIC) percentages were calculated by microtomographic evaluation and histological analysis at one, two, and four weeks after implant placement. ANOVA and Mann–Whitney tests were used for statistical analysis, establishing p < 0.05. No significant differences were found at one-week comparisons. The groups treated with NTLP-ArP obtained higher BIC% than those not treated at two and four weeks. Mechanized surfaces treated with NTLP-ArP obtained BIC values similar to RBM surfacesS

Development of a new preclinical model to study early implant loss: a validation study in the beagle dog

Objectives: To develop a new preclinical model to study early implant loss, where local infection conditions would impair the implant osseointegration. Materials and methods: Forty-eight smooth, 2.9-mm diameter experimental implants were placed in the mandible of 8 beagle dogs (3 in each side). In half of the animals (test group, n = 24 implants), the implants received ligatures around the implant-abutment connection. In the other half, no ligatures were placed (control group, n = 24 implants). Four weeks later, implants were extracted in a flapless approach and standard 3.3-mm diameter SLActive implants were placed into the same osteotomy site without any further drilling. Eight weeks after the second implantation, animals were sacrificed and analyzed in terms of implant survival. Results: After 8 weeks of healing, 4 implants were lost in the control group and 14 in the test group. This corresponded to a 17.4% of early implant loss in the control group and 58.3% in the test. Most of the early failures occurred within the first 5 weeks of healing. Conclusions: Implants placed in a pre-contaminated site present higher early loss than those placed in a non-contaminated site. This study represents a valid and robust preclinical model to study mechanisms and reduction of early implant loss as new technologies become available. Clinical relevance: Scientific rationale for the study: There is lack of animal models to study early implant loss. Thus, a proposal of a new model is presented. With the validation of this model, new technologies can be implemented to prevent early implant lossOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was sponsored by an ITI grant 1111_2015S

Application of shark teeth–derived bioapatites as a bone substitute in veterinary orthopedics. Preliminary clinical trial in dogs and cats

Background: The autograft is still considered the gold standard for the treatment of bone defects. However, given the significant morbidity of the donor site with which it has been associated, alternative substitutes for bone grafts have been developed. In the present study, a bone substitute composed of CaP biphasic bioceramics obtained from shark teeth was used (BIOFAST-VET). Objective: The objective of this study is to evaluate the efficacy of a marine bioapatite in the veterinary clinical field using it as a bone-grafting scaffold in dogs and cats. Methods: The biomaterial was randomly distributed in 6 veterinary clinical centers in Spain and was used in 24 cases (20 dogs and 4 cats) including 14 fractures, 9 arthrodesis, and 1 bone cyst. Grains between 500 and 2,000μm were used. Inclusion and exclusion criteria were established. The time of consolidation and functional recovery were quantitatively and qualitatively assessed. For this, a follow-up was carried out at 2, 4, 8, and 12 weeks, included radiographic images, physical examination and sharing the feedback with the owners. Results: Nineteen cases completed the study (18 dogs and 1 cat; 11 fractures, 7 arthrodesis, and 1 bone cyst). The remaining five were excluded because they did not complete the radiographic follow-up (three cats and two dogs), being three arthrodesis and two fractures. In 18 of 19 cases, the use of the biomaterial was successful; the remaining one failed due to causes not related to the biomaterial. There were no systemic or local adverse reactions. Eighteen patients had a good functional recovery. The average consolidation time was 5.94 weeks in dogs with fractures and arthrodesis, not finding statistically significant differences between sex, weight, and procedure. Conclusions: This biomaterial is presented as a very suitable candidate for orthopedic surgery in the veterinary field. Preliminary results showed that its use reduces consolidation time in dogs with fractures and arthrodesis. In addition, no adverse systemic or local reactions have been observed derived from its use.INTERREG | Ref. 0245 IBEROS1EINTERREG | Ref. 0302 CVMARI1PINTERREG-ATLANTIC AREA | Ref. EAPA_151/2016 BLUEHUMANGAIN | Ref. IN855A2016/06Xunta de Galicia | Ref. ED431C 2017_51Xunta de Galicia | Ref. ED431D 2017/13Xunta de Galicia | Ref. ED431C 2017/3

Case Report: First evidence of a benign bone cyst in an adult Teckel dog treated with shark teeth-derived bioapatites

Bone cysts are a very rare orthopedic pathology in veterinary medicine, the general prevalence of which is unknown. A unicameral bone cyst was diagnosed in an adult female Teckel dog with a limp that was treated surgically by filling the defect with marine bioapatites. The treatment was effective and at 8 weeks the defect had remodeled 50.24%. Eighteen months after surgery, the defect had remodeled 94.23%. The limp disappeared after surgery, and functional recovery was good in all stages after surgery. No adverse reactions were observed at the local or systemic level. This is the first report of a benign bone cyst in an lame adult female Teckel successfully treated with a novel marine bioapatite.Axencia Galega de Innovación | Ref. IN855A2016/06Xunta de Galicia | Ref. ED431C 2017_51Xunta de Galicia | Ref. ED431D 2017/13Xunta de Galicia | Ref. ED431C 2017/37INTERREG-ATLANTIC AREA | Ref. EAPA_151/2016 BLUEHUMANINTERREG | Ref. 0245 IBEROS1EINTERREG | Ref. 0302 CVMARI1