In vivo osseointegration evaluation of implants coated with nanostructured hydroxyapatite in low density bone.

OBJECTIVE: This in vivo study, aimed to biomechanically, histomorphometrically and histologically evaluate an implant surface coated with nanostructured hydroxyapatite using the wet chemical process (biomimetic deposition of calcium phosphate coating) when compared to a dual acid-etching surface. MATERIAL AND METHODS: Ten sheep (2-4 years old) received 20 implants, 10 with nanostructured hydroxyapatite coating (HAnano), and 10 with dual acid-etching surface (DAA). The surfaces were characterized with scanning electron microscopy and energy dispersive spectroscopy; insertion torque values and resonance frequency analysis were measured to evaluate the primary stability of the implants. Bone-implant contact (BIC) and bone area fraction occupancy (BAFo) were evaluated 14 and 28 days after implant installation. RESULTS: The HAnano and DAA groups showed no significant difference in insertion torque and resonance frequency analysis. The BIC and BAFo values increased significantly (p<0.05) over the experimental periods in both groups. This event was also observed in BIC value of HAnano group. The HAnano surface showed superior results compared to DAA after 28 days (BAFo, p = 0.007; BIC, p = 0.01). CONCLUSION: The results suggest that the HAnano surface favors bone formation when compared to the DAA surface after 28 days in low-density bone in sheep.

Does Melatonin Associated with Nanostructured Calcium Phosphate Improve Alveolar Bone Repair?

Background and objectives: Calcium phosphates have been widely used as bone substitutes, but their properties are limited to osteoconduction. The association of calcium phosphates with osteoinductive bioactive molecules has been used as a strategy in regenerative medicine. Melatonin has been studied due to its cell protection and antioxidant functions, reducing osteoclastic activity and stimulating newly formed bone. This study aimed to evaluate the effect of topical application of melatonin associated with nanostructured carbonated hydroxyapatite microspheres in the alveolar bone repair of Wistar rats through histological and histomorphometric analysis. Materials and Methods: Thirty female Wistar rats (300 g) were used, divided randomly into three experimental groups (n = 10), G1: nanostructured carbonated hydroxyapatite microspheres associated with melatonin gel (CHA-M); G2: nanostructured carbonated hydroxyapatite (CHA); G3: blood clot (without alveolar filling). The animals were euthanized after 7 and 42 days of the postoperative period and processed for histological and histomorphometric evaluation. Kruskal-Wallis and Dunn's post-test were applied to investigate statistical differences between the groups at the same time point for new bone and connective tissue variables. Mann-Whitney was used to assess statistical differences between different time points and in the biomaterial variable. Results: Results showed a greater volume of residual biomaterial in the CHA-M than the CHA group (p = 0.007), and there were no significant differences in terms of newly formed bone and connective tissue between CHA and CHA-M after 42 days. Conclusions: This study concluded that both biomaterials improved alveolar bone repair from 7 to 42 days after surgery, and the association of CHA with melatonin gel reduced the biomaterial's biodegradation at the implanted site but did not improve the alveolar bone repair.

Stress as worsening of the signs and symptoms of the geographic tongue during the COVID-19 pandemic: a pilot study.

BACKGROUND: Geographic Tongue (GT) is a benign inflammatory disorder of unknown etiology, which is characterized by the loss of epithelium due to the atrophy of filiform papillae. It usually occurs on the dorsum of the tongue and may extend to its lateral edges. It appears as an erythematous area surrounded by whitish and slightly elevated margins. In most cases, the condition is asymptomatic, although some individuals may report symptoms that include a burning sensation of the tongue. OBJECTIVE: Assess whether there was a change in the clinical aspect of Geographic Tongue (GT) during the COVID-19 pandemic. METHODS: Thirty-two participants were recruited from Dentistry School Universidade Federal Fluminense. Anamnesis and oral examination were performed to collect medical history. The participants were split into two groups: control group (no GT) n = 20 and test group (with GT) n = 12. In the second step, nine participants from a 12 (75%) of the test group were contacted by phone and answered a questionnaire about changes in the signs and symptoms of GT during the pandemic. The subjects were subdivided into two groups: GT with and without signs and symptoms exacerbation. RESULTS: In the first phase of the research, no statistical difference between control and test groups was observed regarding clinical criteria such as age (p + 0.72), gender (p = 0.24), and systemic diseases (p = 0.58). In the second phase, there was a statistical difference between GT groups with or without symptom exacerbation in terms of age and stress as a factor of the oral symptoms (p = 0.3 and 0.2), respectively. Younger patients showed a worsening of the oral lesions related to GT (p = 0.3) and reported stress during the pandemic (p = 0.02). CONCLUSION: Younger patients were more susceptible to stress and presented more exacerbation of the oral lesions related to GT.

In Vivo Evaluation of Permeable and Impermeable Membranes for Guided Bone Regeneration.

BACKGROUND: The degree of biodegradation and the inflammatory response of membranes employed for guided bone regeneration directly impact the outcome of this technique. This study aimed to evaluate four different experimental versions of Poly (L-lactate-co-Trimethylene Carbonate) (PTMC) + Poly (L-lactate-co-glycolate) (PLGA) membranes, implanted in mouse subcutaneous tissue, compared to a commercially available membrane and a Sham group. METHODS: Sixty Balb-C mice were randomly divided into six experimental groups and subdivided into 1, 3, 6 and 12 weeks (n = 5 groups/period). The membranes (1 cm2) were implanted in the subcutaneous back tissue of the animals. The samples were obtained for descriptive and semiquantitative histological evaluation (ISO 10993-6). RESULTS: G1 and G4 allowed tissue adhesion and the permeation of inflammatory cells over time and showed greater phagocytic activity and permeability. G2 and G3 detached from the tissue in one and three weeks; however, in the more extended periods, they presented a rectilinear and homogeneous aspect and were not absorbed. G2 had a major inflammatory reaction. G5 was almost completely absorbed after 12 weeks. CONCLUSIONS: The membranes are considered biocompatible. G5 showed a higher degree of biosorption, followed by G1 and G4. G2 and G3 are considered non-absorbable in the studied periods.

The Use of Hydroxyapatite Loaded with Doxycycline (HADOX) in Dentoalveolar Surgery as a Risk-Reduction Therapeutic Protocol in Subjects Treated with Different Bisphosphonate Dosages.

Medication-related osteonecrosis of the jaw (MRONJ) is considered as a severe adverse side effect of specific drugs such as anti-resorptive and anti-angiogenic medications. Evidence suggests that MRONJ is linked to invasive dental procedures, mainly dentoalveolar surgery. Several preventive strategies to minimize the risk of developing MRONJ have been investigated. However, no investigation has been attempted to evaluate the therapeutic effect of local drug-delivery technology as a preventive strategy protocol. The aim of this study is to evaluate the efficacy of hydroxyapatite-containing doxycycline (HADOX) in rats with high-risk MRONJ development. All the rats used in this study were divided into seven groups. Six groups of rats out of seven were exposed to two different doses of antiresorptive drug therapy for four weeks before undergoing an upper incisor extraction. After 28 days, all the animals were euthanized, and the bone blocks were processed for histological and histomorphometrical evaluation. The histomorphometric analysis confirmed that newly formed bone (NFB) was present in all groups, with significant differences. NFB in the HADOX group treated with zoledronic acid at 4% showed (28.38; C.I. 22.29-34.48), which represents a significant increase compared to HA (15.69; C.I. 4.89-26.48) (p = 0.02). A similar pattern was observed in the HADOX group treated with zoledronic acid 8% ZA treatment (p = 0.001). Conclusions: HADOX did not inhibit any bone repair and reduced early inflammatory response. Hence, HADOX could promote bone healing in patients undergoing antiresorptive drug therapy.

PAX7 gene polymorphism in muscular temporomandibular disorders as potentially related to muscle stem cells.

BACKGROUND: Temporomandibular disorders (TMD) are a group of painful and debilitating disorders, involving the masticatory muscles and/or the temporomandibular joint (TMJ). Chronic TMD pain can be associated with genetic changes in the key muscle development genes. OBJECTIVE: To evaluate the association between polymorphisms in the PAX7 (paired box 7) gene and masticatory myalgia in patients with temporomandibular disorders (TMD). MATERIALS AND METHODS: This is a case-control study. Patients with TMD were divided into two groups: (a) presence of muscular TMD (n = 122) and (b) absence of muscular TMD (n = 49). Genomic DNA was obtained from saliva samples from all participants to allow for genotyping single nucleotide polymorphisms in PAX7 (rs766325 and rs6659735). Over-representation of alleles was tested using chi-square or Fisher's exact tests. Values of p < 0.05 were considered to be statistically significant. RESULTS: Individuals without muscular TMD were less likely to have the PAX7 rs6659735 GG genotype (p = 0.03). No associations were found for PAX7 rs766325. CONCLUSIONS: Alterations in PAX7 may influence muscular pathophysiology and individuals with TMD and the rs6659735 homozygous genotype (GG) are seemingly associated with muscular involvement of the disorder. No associations were found in the region rs766325.

In Vivo Biological Evaluation of Biodegradable Nanofibrous Membranes Incorporated with Antibiofilm Compounds.

Guided bone regeneration involves excluding non-osteogenic cells from the surrounding soft tissues and allowing osteogenic cells originating from native bone to inhabit the defect. The aim of this work was to fabricate, analyze antibiofilm activity and evaluate in vivo biological response of poly (lactic-co-glycolic acid) (PLGA) electrospun membranes incorporated with tea tree oil and furan-2(5H)-one. Samples were exposed to Streptococcus mutans culture and after 48 h incubation, biofilm was evaluated by colony forming units (CFU/mL) followed by scanning electron microscopy. Additionally, seventy-five Balb-C mice were divided into five experimental groups for subcutaneous implantation: tea tree oil loaded PLGA electrospun fiber membrane, furanone loaded PLGA electrospun fiber membrane, neat PLGA electrospun fiber membrane, a commercially available PLGA membrane -Pratix® and Sham (no-membrane implantation). Post implantation period of each experimental group (1, 3 and 9 weeks), samples were collected and processed for by histological descriptive and semiquantitative evaluation. Results showed a significant reduction of bacterial attachment on tea tree oil and furan-2(5H)-one incorporated membranes. Macrophage counts were significant found in all the materials implanted, although giant cells were predominantly associated with electrospun fiber membranes. The incorporation of antibiofilm compounds in nanofibers membranes did not incite inflammatory response significantly different in comparison with pure PLGA electrospun membranes, indicating its potential for development of novel functionalized membranes targeting the inhibition of bacterial biofilms on membrane-grafting materials.

Osseodensification enables bone healing chambers with improved low-density bone site primary stability: an in vivo study.

Primary implant stability is a prerequisite for successful implant osseointegration. The osseodensification technique (OD) is a non-subtractive drilling technique that preserves the bone tissue, increases osteotomy wall density, and improves the primary stability. This study aimed to investigate the hypothesis that OD, through a wider osteotomy, produces healing chambers (HCs) at the implant-bone interface without impacting low-density bone primary stability. Twenty implants (3.5 × 10 mm) with a nanohydroxyapatite (nHA) surface were inserted in the ilium of ten sheep. Implant beds were prepared as follows: (i) 2.7-mm-wide using subtractive conventional drilling (SCD) technique (n = 10); (ii) 3.8-mm-wide using an OD bur system (n = 10). The sheep were randomized to two groups, with samples collected at either 14-(n = 5) or 28-days (n = 5) post-surgery and processed for histological and histomorphometric evaluation of bone-implant contact (BIC) and bone area fraction occupancy (BAFO). No significant group differences were found with respect to final insertion torque and implant stability quotient (p > 0.050). BIC values were higher for SCD after 14 and 28 days (p < 0.050); however, BAFO values were similar (p > 0.050). It was possible to conclude that the OD technique allowed a wider implant bed preparation without prejudice on primary stability and bone remodeling.

Analysis of Active Oral Tactile Sensitivity in Individuals with Complete Natural Dentition.

AIM: To evaluate the active tactile sensitivity in individuals with complete natural dentition, determining the smallest thickness detected by the participants, and clarifying if there is a difference between the thicknesses analyzed. MATERIALS AND METHODS: Active tactile sensitivity was evaluated in 40 research participants. Inclusion criteria included participants with complete natural dentition, without active or history of periodontal disease, absence of temporomandibular disorders, bruxism, and restorations in the evaluated area. Exclusion criteria included age below 18 years. The active tactile perception threshold was evaluated by using carbon sheets of different thicknesses (0, 12, 24, 40, 80, 100, and 200 µm), which were inserted in the participants' premolars, bilaterally. The carbon sheet was inserted so as not to come into contact with the oral soft tissues. Subsequently, the participant occluded and was asked about the perception of the intraocclusal object 20 times in each occlusal contact. The collected data were tabulated considering the amount of positive and negative responses for each carbon thickness. Values of p < 0.05 were considered significant. RESULTS: The results showed that there was linearity in perception, on both sides, besides, the natural dentition was able to perceive difference in thickness from 12 µm. CONCLUSION: We conclude that the 12 µm thickness is noticeable in occlusion and can be differentiated from other thicknesses in natural dentition and that there is no difference between the tactile sensitivity of the right and left sides. CLINICAL SIGNIFICANCE: A better understanding of active oral tactile sensitivity will contribute to numerous clinical applications in dentistry, including occlusal adjustment in dental rehabilitation, dental implants prosthesis design, and survival of prosthetic rehabilitation.

The risk of osteonecrosis of the jaw and adverse outcomes in patients using antiresorptive drugs undergoing orthodontic treatment: A systematic review.

OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) is rare. It is a serious adverse effect of certain drugs, of which bisphosphonates (BPs) are the most widely known. The aim of this systematic review was to analyze all published evidence for the reported adverse outcomes as a result of orthodontic treatment in patients undergoing antiresorptive therapy. DATA: All types of studies involving patients undergoing orthodontic treatment and treated with antiresorptive drugs were considered. A meta-analysis was not conducted due to the high amount of variability and heterogeneity in the reporting and presentation of data among the studies meeting the inclusion criteria. SOURCES: A systematic search was performed using 4 databases (PubMed, MEDLINE, EMBASE and CINAHL). STUDY SELECTION: Seven studies matched the inclusion criteria for this review, reporting a total of 29 patients. MRONJ was only reported in 1 patient. The adverse outcomes following orthodontic treatment included difficulty achieving root parallelism (n = 4), difficulty achieving complete space closure (n = 3), exaggerated tooth mobility post-debond (n = 2), increased duration of orthodontic treatment beyond expected completion (n = 1), sclerotic alveolar bone changes seen on post-op radiographic images (n = 2), and an increased amount of root resorption (n = 1). CONCLUSIONS: The high amount of heterogeneity and limited evidence precluded a valid interpretation and analysis of the results through pooling of data. Additional data with sufficient quality, a reduction of bias, and a greater prospective cohort of patients is crucial to assess adverse effects, mechanisms of action, and associated risk factors in at-risk patients. CLINICAL SIGNIFICANCE: Based on the limited evidence available in the literature, it is unclear whether orthodontic treatment alone can precipitate MRONJ. However, antiresorptive drug therapy may be associated with a sub-optimal treatment outcome.

In Vitro and In Vivo Evaluation of Nanostructured Biphasic Calcium Phosphate in Granules and Putty Configurations.

Synthetic biphasic calcium phosphate (BCP) granules and powder are biocompatible biomaterials with a well-known capacity for osteoconduction, presenting very satisfactory clinical and histological results. It remains unanswered if the putty configuration impacts the biological response to the material. In this study, we aimed to compare the cytocompatibility and biocompatibility of nanostructured BCP in the putty configuration (moldable nanostructured calcium phosphate, MnCaP) on the healing of critical-sized bone defects (8 mm) in rat calvaria. Cytocompatibility was determined through the viability of fibroblast cells (V-79) to the extracts of different concentrations of MnCaP. Forty-five Wistar rats were randomly divided into three groups (n = 15)-clot, MnCaP, and commercial biphasic calcium phosphate in granules configurations (Nanosynt®)-and subdivided into three experimental periods (1, 3, and 6 months). Histological, histomorphometric, and microtomographic analyses allowed the evaluation of newly formed bone, residual biomaterial, and connective tissue. The in vitro evaluation showed that MnCaP was cytocompatible. The histomorphometric results showed that the Nanosynt® group granted the highest new-formed bone values at six months (p < 0.05), although the biomaterial volume did not differ between groups. The putty configuration was easier to handle, and both configurations were biocompatible and osteoconductive, presented similar biosorption rates, and preserved the calvaria architecture.

Weak evidence for the management of medication-related osteonecrosis of the jaw: An overview of systematic reviews and meta-analyses.

BACKGROUND: Although several therapies are proposed for medication-related osteonecrosis of the jaw (MRONJ), to date there is no consensus or treatment protocol for MRONJ. This overview aims to summarize the available evidence on the management and outcomes of MRONJ. METHODS: An electronic search without language or date restrictions occurred in five databases and gray literature for articles published until March 2020. This overview was performed according to the PICO format. The eligibility criteria comprised systematic reviews (RS) with or without meta-analyses that analyzed treatments outcomes for MRONJ. The methodological quality of each SR was evaluated using AMSTAR 2. RESULTS: Fifteen studies published between 2014 and 2020 were included in this overview. The summary of the evidence showed that conservative treatment and low level laser therapy can yield favorable results for early stages of MRONJ whereas surgical treatment seems to be better for advanced stages. However, qualitative assessment of the SRs highlighted a global low level of quality. CONCLUSIONS: There is weak evidence to support treatment protocols for MRONJ. Because of the low quality of the SRs, highlighted by this overview, no insightful therapeutic recommendations can be issued for any intervention for MRONJ.

In Vivo Comparative Evaluation of Biocompatibility and Biodegradation of Bovine and Porcine Collagen Membranes.

Mechanical barriers prevent the invasion of the surrounding soft tissues within the bone defects. This concept is known as Guided Bone Regeneration (GBR). The knowledge about the local tissue reaction and the time of degradation of absorbable membranes favors the correct clinical indication. This study aimed to evaluate the biocompatibility and biodegradation of a bovine collagen membrane (Lyostypt®, São Gonçalo, Brazil) and compare it to a porcine collagen membrane (Bio-Gide®) implanted in the subcutaneous tissue of mice, following ISO 10993-6:2016. Thirty Balb-C mice were randomly divided into three experimental groups, LT (Lyostypt®), BG (Bio-Gide®), and Sham (without implantation), and subdivided according to the experimental periods (7, 21, and 63 days). The BG was considered non-irritant at seven days and slight and moderate irritant at 21 and 63 days, respectively. The LT presented a small irritant reaction at seven days, a mild reaction after 21, and a reduction in the inflammatory response at 63 days. The biodegradation of the LT occurred more rapidly compared to the BG after 63 days. This study concluded that both membranes were considered biocompatible since their tissue reactions were compatible with the physiological inflammatory process; however, the Bio-Gide® was less degraded during the experimental periods, favoring the guided bone regeneration process.

Nanostructured Carbonated Hydroxyapatite Associated to rhBMP-2 Improves Bone Repair in Rat Calvaria.

Many biomaterials are used for Bone Morphogenetic Proteins (BMPs) delivery in bone tissue engineering. The BMP carrier system's primary function is to hold these growth factors at the wound's site for a prolonged time and provide initial support for cells to attach and elaborate the extracellular matrix for bone regeneration. This study aimed to evaluate the nanostructured carbonated hydroxyapatite microspheres (nCHA) as an rhBMP-2 carrier on rats calvaria. A total of fifteen male Wistar rats were randomly divided into three groups (n = 5): clot (control group), rhBMP-2 associated with collagen membrane (COL/rhBMP-2) or associated with the microspheres (nCHA/rhBMP-2). After 45 days, the calvaria defect samples were evaluated through histological, histomorphometric, and SR-µCT analyses to investigate new-formed bone and connective tissue volume densities. The descriptive histological analysis showed that nCHA/rhBMP-2 improved bone formation compared to other groups. These results were confirmed by histomorphometric and SR-µCT analysis that showed substantially defect area filling with a higher percentage of newly formed (36.24 ± 6.68) bone than those with the COL/rhBMP-2 (0.42 ± 0.40) and Clot (3.84 ± 4.57) (p < 0.05). The results showed that nCHA is an effective carrier for rhBMP-2 encouraging bone healing and an efficient alternative to collagen membrane for rhBMP-2 delivery.

The Influence of Nanostructured Hydroxyapatite Surface in the Early Stages of Osseointegration: A Multiparameter Animal Study in Low-Density Bone.

BACKGROUND AND OBJECTIVE: The success rates of dental implants in low-density bone have been reported as a challenge, especially for early or immediate loading in the maxilla posterior area. Nanoscale architecture affects the roughness, surface area, surface energy of the implant and can enhance osseointegration. This study aimed to evaluate the implant-surface topography and biomechanical, histomorphometric, and histological bone responses to a new nanostructured hydroxyapatite surface placed in the iliac crest of sheep. METHODS: Ten female sheep (2-4 years) received 30 implants (n=10/group): HAnano® coated (Epikut Plus®, S.I.N. Implant System, Sao Paulo, SP, Brazil), SLActive (BLX®, Straumann, Basel, Switzerland), and TiUnite (NobelActive®, Nobel Biocare, Göteborg, Sweden) surfaces. Scanning electron microscopy with energy-dispersive spectroscopy evaluated the implant surface topography, the insertion torque value, and resonance frequency analysis evaluated the primary stability, bone-implant contact, and bone-area fraction occupancy were evaluated after 14 and 28 days after implant placement. RESULTS: The surface morphology was considerably comparable between the implant groups'; however, the TiUnite® group presented a remarkable different surface. The SLActive® and TiUnite® groups presented an insertion torque average of 74 (±8.9) N/cm that was similar to that of HAnano® 72 (±8.3) N/cm (p >0.05). The resonance frequency evaluated with Osstell®/SmartPeg® or Penguin®/MulTipeg® showed similar results when assessing implants from the same group. BIC and BAFO significantly increased (p<0.05) throughout the experimental periods to all groups, but BIC and BAFO values were similar among the implants at the same time point. After 4 weeks, bone-implant contact was higher than 80% of the total length analyzed. New bone occupies around 60% of analyzed area around the implants. CONCLUSION: HAnano® coated surface promoted comparable osseointegration as SLActive and TiUnite in the sheep model. The three tested surfaces showed comparable osseointegration at the early stages of low-density bone repair in the sheep model.

In Vivo Biological Evaluation of Orthodontically Moved Incisors after Replantation.

Background and Objectives: There is still considerable controversy regarding the possibility of submitting replanted teeth to orthodontic movement (OM). The purpose of the present study was to evaluate the tissue response after orthodontic movement on replanted teeth. Materials and Methods: Sixty Wistar rats were randomly assigned to four groups (n = 15): G1, replantation without OM after 30 days; G2, replantation with OM after 30 days; G3, replantation without OM after 60 days, and G4, replantation with OM after 60 days. The maxillary left central incisors were extracted and the teeth were stored in milk media. After 30 min, the teeth were replanted and fixed with non-rigid immobilization. All specimens were observed after 30 and 60 days of replantation and then subdivided into two subgroups (with OM or without OM). The animals were euthanized after seven days of the OM started, and the maxillary bone blocks were processed for histological evaluation. Results: The histological results showed periodontal ligament repair in both periods studied without OM; however, ankylosis and root resorption was seen in all orthodontically moved teeth. Conclusions: The orthodontic movement did not favor tissue response in all replanted teeth, regardless of the experimental periods.

Calcium Phosphate Carrying Simvastatin Enhances Bone Regeneration: A Systematic Review.

Several studies have aimed to develop alternative therapeutic biomaterials for bone repair. The purpose of this systematic review was to evaluate how statins carried by calcium phosphate affect the formation and regeneration of bone tissue in animal models when compared to other biomaterials or spontaneous healing. This systematic review followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, the PRISMA guidelines, and the Preclinical Systematic Review & Meta-analysis Facility (SyRF). The protocol of this systematic review was registered in PROSPERO (CRD42018091112) and in CAMARADES. In addition, ARRIVE checklists were followed in order to increase the quality and transparency of the search. An electronic search was performed using the MEDLINE/PubMed, Scopus, SciELO, and PROSPERO library databases. The authors used a specific search strategy for each database, and they also conducted a search in the grey literature and cross-references. The eligibility criteria were animal studies, which evaluated bone repair treated with calcium phosphate as a simvastatin carrier. The selection process yielded 8 studies from the 657 retrieved. All manuscripts concluded that locally applied simvastatin carried by calcium phosphate is biocompatible, enhanced bone repair and induced statistically greater bone formation than cloth or calcium phosphate alone. In conclusion, the pertinent pre-clinical studies evidenced the calcium phosphate biocompatibility and its effectiveness in delivering SIM to improve the repair of bone defects. So, clinical trials are encouraged to investigate the impact of SIM associated with calcium phosphate bone graft in repairing bone defect in humans.

Calcium phosphate carrying simvastatin enhances bone regeneration: a systematic review

Abstract Several studies have aimed to develop alternative therapeutic biomaterials for bone repair. The purpose of this systematic review was to evaluate how statins carried by calcium phosphate affect the formation and regeneration of bone tissue in animal models when compared to other biomaterials or spontaneous healing. This systematic review followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, the PRISMA guidelines, and the Preclinical Systematic Review & Meta-analysis Facility (SyRF). The protocol of this systematic review was registered in PROSPERO (CRD42018091112) and in CAMARADES. In addition, ARRIVE checklists were followed in order to increase the quality and transparency of the search. An electronic search was performed using the MEDLINE/PubMed, Scopus, SciELO, and PROSPERO library databases. The authors used a specific search strategy for each database, and they also conducted a search in the grey literature and cross-references. The eligibility criteria were animal studies, which evaluated bone repair treated with calcium phosphate as a simvastatin carrier. The selection process yielded 8 studies from the 657 retrieved. All manuscripts concluded that locally applied simvastatin carried by calcium phosphate is biocompatible, enhanced bone repair and induced statistically greater bone formation than cloth or calcium phosphate alone. In conclusion, the pertinent pre-clinical studies evidenced the calcium phosphate biocompatibility and its effectiveness in delivering SIM to improve the repair of bone defects. So, clinical trials are encouraged to investigate the impact of SIM associated with calcium phosphate bone graft in repairing bone defect in humans.

Resumo Muitos estudos objetivaram desenvolver biomateriais terapêuticos alternativos para o reparo ósseo. O objetivo desta revisão sistemática foi avaliar o efeito da estatina carreada por fosfato de cálcio na formação e regeneração de tecido ósseo em modelos animais quando comparado com outros biomateriais ou coágulo. Esta revisão sistemática seguiu as recomendações do Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines, e o Preclinical Systematic Review & Meta-analysis Facility (SyRF). O protocolo desta revisão sistemática foi registrado no PROSPERO (CRD42018091112) e no CAMARADES. Além disso, o guia ARRIVE foi utilizado com o objetivo de aumentar a qualidade e transparência do estudo. Uma pesquisa eletrônica foi realizada através do MEDLINE/PubMed, Scopus, SciELO, e biblioteca do PROSPERO. Os autores utilizaram uma estratégia de busca específica para cada base de dados, e uma busca foi conduzida na literatura cinza e nas referências dos artigos selecionados. Os critérios de elegibilidade foram estudos em animais, os quais avaliaram o repara do ósseo tratado com fosfato de cálcio como carreador de estatina. O processo de seleção obteve 8 estudos dos 657 encontrados. Todos os estudos concluíram que a aplicação local da sinvastatina carreada pelo fosfato de cálcio é biocompatível, melhora o reparo ósseo e induz uma formação óssea significantemente maior que coágulo ou fosfato de cálcio sozinho. Em conclusão, os estudos pré-clínicos pertinentes evidenciaram a biocompatibilidade do fosfato de cálcio e sua eficácia na entrega do SIM para melhorar o reparo de defeitos ósseos. Assim, estudos clínicos são encorajados a investigar o impacto do SIM associado ao enxerto ósseo de fosfato de cálcio na reparação de defeito ósseo em humanos.

Randomized Controlled Clinical Trial of Nanostructured Carbonated Hydroxyapatite for Alveolar Bone Repair.

The properties of the biodegradation of bone substitutes in the dental socket after extraction is one of the goals of regenerative medicine. This double-blind, randomized, controlled clinical trial aimed to compare the effects of a new bioabsorbable nanostructured carbonated hydroxyapatite (CHA) with a commercially available bovine xenograft (Bio-Oss®) and clot (control group) in alveolar preservation. Thirty participants who required tooth extraction and implant placement were enrolled in this study. After 90 days, a sample of the grafted area was obtained for histological and histomorphometric evaluation and an implant was installed at the site. All surgical procedures were successfully carried out without complications and none of the patients were excluded. The samples revealed a statistically significant increase of new bone formation (NFB) in the CHA group compared with Bio-Oss® after 90 days from surgery (p < 0.05). However, the clot group presented no differences of NFB compared to CHA and Bio-Oss®. The CHA group presented less amount of reminiscent biomaterial compared to Bio-Oss®. Both biomaterials were considered osteoconductors, easy to handle, biocompatible, and suitable for alveolar filling. Nanostructured carbonated hydroxyapatite spheres promoted a higher biodegradation rate and is a promising biomaterial for alveolar socket preservation before implant treatment.