Current Emerging Concepts on the Pathogenesis of Peri-implant Diseases: A Narrative Review.

OBJECTIVES: The aim of this narrative review is to describe the emerging evidence concerning etiological factors and pathophysiological mechanisms involved in peri-implant inflammatory diseases. MATERIAL AND METHODS: An electronic search for articles published until November 2022 was conducted in MEDLINE by three independent reviewers to identify manuscripts reporting data on etiological factors and pathophysiological mechanisms associated with peri-implant diseases. RESULTS: Current evidence suggests that peri-implant mucositis and peri-implantitis are inflammatory conditions linked to a microbial challenge. However, in recent years, there has been increasing evidence indicating that certain peri-implant inflammatory conditions may not be primarily related to biofilm-mediated infectious processes but rather to other biological mechanisms, such as a foreign body response. CONCLUSION: The current evidence, not only in the dental literature, opens new avenues for a more complex interpretation of the etiopathogenetic factors involved in peri-implant diseases. A better understanding of various factors related to the host response, including dysbiosis mechanisms associated with changes in microbiota composition, is necessary for a more precise physiopathological characterization of these diseases.

IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas.

INTRODUCTION: Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) over-expression is a predictor of tumor recurrence and metastases in some types of human melanoma. Our objective was to evaluate the immunohistochemical expression of IMP3 and other molecules related to tumor prognosis in melanoma-xeno-tumors undergoing treatment. We test the effect of radiotherapy (RT) and mesenchymal stromal cells (MSCs) treatment, analyzing the tumorigenic and metastatsizing capacity in a mice melanoma xenograft model. MATERIALS AND METHODS: We inoculated A375 and G361 human melanoma cell lines into NOD/SCID gamma mice (n = 64). We established a control group, a group treated with MSCs, a group treated with MSCs plus RT, and a group treated with RT. We assessed the immunohistochemical expression of IMP3, E-cadherin, N-cadherin, PARP1, HIF-1α, and the proliferation marker Ki-67. Additionally, we performed a retrospective study including 114 histological samples of patients diagnosed with malignant cutaneous superficial spreading melanoma (n = 104) and nodular melanoma (n = 10) with at least 5 years of follow-up. RESULTS: Most morphological and immunohistochemical features show statistically significant differences between the 2 cell lines. The A375 cell line induced the formation of metastases, while the G361 cell line provoked tumor formation but not metastases. All three treatments reduced the cell proliferation evaluated by the Ki-67 nuclear antigen (p = 0.000, one-way ANOVA test) and reduced the number of metastases (p = 0.004, one-way ANOVA test). In addition, the tumor volumes reduced in comparison with the control groups, 31.74% for RT + MSCs in the A357 tumor cell line, and 89.84% RT + MSCs in the G361 tumor cell line. We also found that IMP3 expression is associated with greater tumor aggressiveness and was significantly correlated with cell proliferation (measured by the expression of Ki-67), the number of metastases, and reduced expression of adhesion molecules. CONCLUSIONS: The combined treatment of RT and MSCs on xenografted melanomas reduces tumor size, metastases frequency, and the epithelial to mesenchymal transition/PARP1 metastatic phenotype. This treatment also reduces the expression of molecules related to cellular proliferation (Ki-67), molecules that facilitate the metastatic process (E-cadherin), and molecules related with prognosis (IMP3).

Periostin in the relation between periodontal disease and atherosclerotic coronary artery disease: A pilot randomized clinical study.

OBJECTIVE: The aim of this study was to analyze the effects of periodontal treatment on markers of atherosclerotic coronary artery disease and circulating levels of periostin. BACKGROUND: Periostin is necessary for periodontal stability, but it is highly present in atherosclerotic plaques. Treatment of periodontal disease, with low levels of local periostin, is thought to reduce systemic levels of periostin. Thus, this may contribute to cardiovascular health. METHODS: A pilot randomized controlled clinical trial was designed to include patients with severe periodontal disease and history of atherosclerotic coronary artery disease. Samples of gingival crevicular fluid (GCF) and serum were collected before and after periodontal treatment by periodontal surgery or non-surgical therapy. The levels of several markers of inflammation and cardiovascular damage were evaluated including CRP, IFN-γ, IL-1ß, IL-10, MIP-1α, periostin, and TNF-α in GCF and CRP, Fibrinogen, IFN-γ, IL-1ß, IL-6, IL-10, L-Selectin, MIP-1α, Periostin, TNF-α, and vWF in serum. RESULTS: A total of 22 patients with an average of 56 years old were recruited for participating in this study. Twenty of them were male. Most of them (82%) had suffered an acute myocardial event and underwent surgery for placing 1, 2, or 3 stents in the coronary arteries more than 6 months ago but less than 1 year. The treatment of periodontal disease resulted in an overall improvement of all periodontal parameters. Regarding the evaluation of GCF and serum, a significant increase of periostin in the GCF was observed after periodontal surgery. In contrast, although other markers in GCF and serum improved, no significant correlations were found. CONCLUSION: Treatment of periodontal disease through periodontal surgery induces a local and transient increase in the levels of periostin in the gingival crevicular fluid. The effects on systemic markers of inflammation and cardiovascular function have not been confirmed.

Emerging factors affecting peri-implant bone metabolism.

Implant dentistry has evolved to the point that standard implant osseointegration is predictable. This is attributed in part to the advancements in material sciences that have led toward improvements in implant surface technology and characteristics. Nonetheless, there remain several cases where implant therapy fails (specifically at early time points), most commonly attributed to factors affecting bone metabolism. Among these patients, smokers are known to have impaired bone metabolism and thus be subject to higher risks of early implant failure and/or late complications related to the stability of the peri-implant bone and mucosal tissues. Notably, however, emerging data have unveiled other critical factors affecting osseointegration, namely, those related to the metabolism of bone tissues. The aim of this review is to shed light on the effects of implant-related factors, like implant surface or titanium particle release; surgical-related factors, like osseodensification or implanted biomaterials; various drugs, like selective serotonin reuptake inhibitors, proton pump inhibitors, anti-hypertensives, nonsteroidal anti-inflammatory medication, and statins, and host-related factors, like smoking, diet, and metabolic syndrome on bone metabolism, and aseptic peri-implant bone loss. Despite the infectious nature of peri-implant biological complications, these factors must be surveyed for the effective prevention and management of peri-implantitis.

Preclinical Evidence for the Use of Oral Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone Regenerative Therapy: A Systematic Review.

The development of extracellular vesicles (EVs) therapies has revolutionized personalized medicine, opening up new possibilities for treatment. EVs have emerged as a promising therapeutic tool within this field due to their crucial role in intercellular communication across various cell types and organisms. This systematic review aims to evaluate the therapeutic potential of oral mesenchymal stem cell (MSC)-derived EVs for bone regeneration, specifically focusing on findings from preclinical models. Sixteen articles meeting the inclusion criteria were selected following document analysis. The biological effects of oral MSC-derived EVs predominantly involve the upregulation of proteins associated with angiogenesis, and inflammation resolution, alongside the downregulation of proinflammatory cytokines. Moreover, these therapeutic agents have been found to contain a significant quantity of different molecules (proteins, lipids, DNA, microRNAs, etc) further contributing to their modulatory potential. The findings from this systematic review underscore that oral MSC-derived EVs, irrespective of their specific population, have the ability to enhance the osteogenic repair response in maxillary bone or periodontal defects. In summary, this systematic review highlights the promising potential of oral MSC-derived EVs for bone regeneration based on evidence from preclinical models. The comprehensive assessment of their biological effects and the presence of microRNAs underscores their therapeutic significance. These findings support the utilization of oral MSC-derived EVs in enhancing the osteogenic repair response in various maxillary bone or periodontal defects, providing insights into the mechanisms involved and potential therapeutic applications in the field of personalized medicine.

Inflammasomes NLRP3 and AIM2 in peri-implantitis: A cross-sectional study.

BACKGROUND: Inflammasome components NLRP3 and AIM2 contribute to inflammation development by the activation of caspase-1 and IL-1ß. They have not been yet evaluated in samples from patients with active peri-implantitis. Thus, the aim of the present study is to analyze the expression of inflammasomes NLRP3 and AIM2 and subsequent caspase 1 and IL-1ß assessing the microenvironment of leukocyte subsets in samples from patients with active peri-implantitis. METHODS: Biopsies were collected from 33 implants in 21 patients being treated for peri-implantitis. Biopsies from gingival tissues from 15 patients with healthy periodontium were also collected for control. These tissues were evaluated through conventional histological stainings. Then, immunohistochemical detection was performed to analyze NLRP3, AIM2, caspase-1, and IL-1ß and markers of different leukocyte subsets. PCR for inflammasomes and related genes was also done. RESULTS: This manuscript reveals a high immunohistochemical and mRNA expression of NLRP3 and AIM2 inflammasomes, caspase-1, and IL-1ß in biopsies collected from human peri-implantitis. The expression of the tested markers was significantly correlated with the increase in inflammatory infiltrate, probing depth, presence of biofilm, and bleeding on probing. In these peri-implantitis lesions, the area of biopsy tissue occupied by inflammatory infiltrate was intense while the area occupied by collagen was significantly lower. In comparison with periodontal healthy tissues, the inflammatory infiltrate was statistically significantly higher in the peri-implantitis biopsies and was mainly composed of plasma cells, followed by T and B lymphocytes. CONCLUSION: In human peri-implantitis, chronic inflammation can be explained in part by the action of IL-1ß/caspase 1 induced through NLRP3 and AIM2 inflammasome activation.

Screw-retained internal connection zirconia CAD-CAM abutments in single implant reconstructions: Results of a 1-year prospective case series study.

PURPOSE: To evaluate the clinical and radiographic outcomes of single-tooth implant restorations using one-piece, internally connected, screw-retained, computer-aided design and computer-aided manufactured monolithic zirconia restorations fabricated on regular diameter implants. MATERIAL AND METHODS: Following a 2-stage surgical procedure, 22 implants placed in anterior and posterior areas in 21 partially edentulous patients (mean age of 55 years; 9 males/12 females) were evaluated in terms of plaque index, pocket probing depth, bleeding on probing, level of oral hygiene (OH), signs of mucositis/peri-implantitis, esthetic score (ES), gingival zenith position (GZP), papilla index score, the thickness of peri-implant gingiva, radiographic marginal bone loss, and technical complications. Implants and restorations were prospectively followed from the insertion of the restoration (baseline), up to 12-months post-loading. RESULTS: A 100% implant survival rate resulted after loading; one implant was lost before loading. Clinically, patients performed an adequate OH, and tissues were kept healthy. Probing depth showed a slightly lower value at baseline compared to any follow-up examination (2.26 [0.94] at baseline vs. 2.53 [0.66] mm at 12 months). ES, GZP, and the thickness of the peri-implant gingiva improved throughout the course of the study. Radiographically, average marginal bone level (MBL) was 0.40 (0.40) mm after 1-year follow-up with no differences in average MBL at all time points. Technically, after 1 year of clinical function, neither abutment fracture nor any other serious complications occurred. Hence, prosthetic reconstruction survival rate was 100%. CONCLUSIONS: Clinical outcomes of single-tooth implant restorations using internally connected, screw-retained, computer-aided design and computer-aided manufacturing monolithic zirconia abutments can be considered a reliable treatment alternative after 1-year clinical observation.

Physico-chemical and biological characterization of a new bovine bone mineral matrix available for human usage.

BACKGROUND: Anorganic bovine bone has been deeply studied for bone regeneration in the oral cavity. Different manufacturing processes can modify the final composition of the biomaterial and the responses that induce. AIM: To evaluate the physico-chemical characteristics of a bovine bone mineral matrix and the clinical, radiographical, histological, and mRNA results after using it for maxillary sinus floor augmentation in humans. MATERIALS AND METHODS: First, the physical-chemical characteristics of the biomaterial were evaluated by X-ray powder diffraction, X-ray fluorescence, and electron microscopy. A frequently used biomaterial with the same animal origin was used as comparator. Then, a clinical study was designed for evaluating clinical, radiographical, histological, and mRNA outcomes. Patients in need of two-stage maxillary sinus floor augmentation were included in the study. Six months after the grafting procedure, a bone biopsy was collected for evaluation. RESULTS: In terms of physico-chemical characteristics, no differences were found between both biomaterials. Clinically, 10 patients were included in the study. After 6 months, clinical and radiographical data showed adequate outcomes for allowing implant placement. Histological, immunohistochemical and mRNA analyses showed that the biomaterial in use provides biological support to induce responses similar to those of other commonly used biomaterials. CONCLUSION: Bovine bone mineral matrix (Creos™ Xenogain) used as a single material for maxillary sinus floor augmentation shows adequate biological, clinical, and radiological outcomes. In fact, the results from this study are similar to those reported in the literature for another bovine bone-derived biomaterial with whom it shares composition and micro- and nanoscale characteristics.

Limited marginal bone loss in implant-supported fixed full-arch rehabilitations after 5 years of follow-up.

PURPOSE: The aim of the present study was to evaluate the 5-year results in terms of marginal bone level (MBL) around implants supporting fixed full-arch metal-ceramic restorations in a series of cases of patients who had lost their teeth in that dental arch because of severe periodontal disease. MATERIAL AND METHODS: A retrospective cohort study was designed to evaluate the 5-year MBL results of OsseoSpeed™ Astra Tech TX implants with internal tapered conical connection. Age, gender, bone substratum, smoking habits, history of periodontitis, and prosthetic features were recorded. Mixed linear model was used to determine the influence of the different variables on MBL. RESULTS: In this series, a total of 160 implants placed in 19 patients were evaluated. No implant failure was reported during the 5 years of follow-up. Only 14 (8.75%) implants had more than 2 mm of MBL. Abutment height, F(3,142) = 6.917, p < .001, and implant diameter, F(1,141) = 15.059, p < .001, were determined to be statistically associated with MBL. No other effect was significant. Pairwise comparisons showed that MBL was larger for abutment height = 1 (MBL = -0.987, SE = 0.186) compared with the remaining heights [-0.335 (0.171), -0.169 (0.192) and -0.247 (0.267), 2, 4 and 6 mm, respectively]. MBL was larger for narrow (-0.510, SE = 0.169) than for wide implants (-0.364, SE = 0.190). CONCLUSION: The current study demonstrates that the vast majority of internal conical connection implants supporting fixed full-arch metal-ceramic restorations do not suffer from relevant MBL after 5 years in function. Particularly, those implants with transmucosal abutments longer than 2 mm show less than 0.5 mm from the implant shoulder to the marginal bone.

Early marginal bone loss around dental implants to define success in implant dentistry: A retrospective study.

PURPOSE: The aim of this study was to establish an objective criterion in terms of marginal bone level (MBL) to know the prognosis of an implant. MATERIALS AND METHODS: A group of 176 patients in whom 590 implants were placed were included in this retrospective study. Patients older than 18 years, presenting either Kennedy class I or II edentulous section, or totally edentulous at least in one of the dental arches were included in this study. Those with any type of disturbance able to alter bone metabolism or with nontreated periodontal disease were excluded. Data on radiographic MBL at loading, 6 and 18 months later, age, gender, smoking habits, history of periodontitis, bone substratum, implant, and prosthetic features were recorded. Nonparametric receiver operating curves (ROC) were constructed for the MBL at 18 months in order to establish a distinction among high bone loser (HBL) and low bone loser (LBL) implants. Differences as a function of main variables were also determined, particularly abutment height and periodontal disease. RESULTS: HBL implants lost at least 0.48 mm of MBL 6 months after loading; they reached at least 2 mm of MBL 18 months after loading. MBL rate followed a nonlinear trend, except in implants restored over long prosthetic abutments and in patients with history of severe periodontitis; in whom the rate of MBL over the time was nearly zero. CONCLUSION: Implants that lose more than 0.5 mm of marginal bone 6 months after loading are at great risk of not being radiographically successful anymore. Therefore, 0.5 mm of MBL is proposed as a distinctive and objective criterion of success in Implant Dentistry within a 6-month follow-up period. A prosthetic abutment height ≥2 mm resulted the most protective factor in the peri-implant bone maintenance.

Anorganic Bovine Bone Plus Recombinant Human Platelet-Derived Growth Factor-BB in Ridge Preservation: A Pilot Study.

PURPOSE: To determine clinical parameters, histologic features, and radiographic linear bone width changes of regenerated bone using different biomaterials for ridge preservation following tooth extraction. MATERIALS AND METHODS: For this pilot study, five patients were grafted with anorganic bovine bone and collagen plus recombinant human platelet-derived growth factor-BB (rhPDGF-BB), five patients were grafted with anorganic bovine bone and collagen alone, and five patients did not receive any biomaterial (control) after tooth extraction. Clinical, histologic, and radiographic evaluations were carried out 4 months postextraction. RESULTS: Differences in terms of buccolingual width were found when comparing the control group to the group grafted with anorganic bovine bone and collagen plus rhPDGF-BB (P = .012). No statistical differences were observed between the groups in terms of mineralized or nonmineralized tissue formation or in terms of the number of osteoblasts or osteocytes per mm2 after 4 months of healing. Interestingly, the number of vessels in the grafted area was found to be significantly different among the three groups (P = .005). The number of Musashi-1 positive cells was also different among groups, both in the mineralized and the nonmineralized areas of the grafted bone (P = .024 and .005, respectively). CONCLUSION: Anorganic bovine bone with bovine collagen is an efficient biomaterial to avoid postextraction resorption of the alveolar ridge. The addition of rhPDGF-BB appears to improve the biologic features of the newly formed bone and decrease bone resorption; further studies are needed for confirmation.

Prognostic factors associated with implant loss, disease progression or favorable outcomes after peri-implantitis surgical therapy.

BACKGROUND: The treatment of the peri-implantitis remains complex and challenging with no consensus on which is the best treatment approach. PURPOSE: To examine the key local and systemic factors associated with implant loss, disease progression, or favorable outcomes after surgical peri-implantitis therapy. MATERIALS AND METHODS: Records of patients treated for peri-implantitis were screened. Patient-, implant- and surgery-related variables on and prior to the day of the surgery were collected (T0: time of peri-implantitis treatment). If the treated implant was still in function when the data was collected, the patient invited to participate for a recall study visit (T1, longest follow-up after treatment). Impacts of the variables on the implant survival, success, and peri-implant bone change after treatment were investigated. RESULTS: Eighty patients with 121 implants with a mean follow-up of 42.6 ± 26.3 months were included. A total of 22 implants (18.2%) were removed during the follow-up period. When relative bone loss (%) was in range 25%-50%, risk for implant removal increased 15 times compared to lower bone loss <25% (OR = 15.2; CI: 2.06-112.7; p = 0.008). Similarly, relative bone loss of >50% increased 20 times the risk of implant failure compared to the <25% (OR = 20.2; CI: 2.42-169.6; p = 0.006). For post-treatment success rate, history of periodontitis significantly increased the risk of unsuccess treatment (OR = 3.07; p = 0.04) after resective surgery). CONCLUSION: Severe bone loss (>50%) poses significantly higher risk of treatment failure.

The impact of tooth loss on cognitive function.

OBJECTIVE: To investigate if there is epidemiological evidence of an association between edentulism and cognitive decline beside that currently available from limited sample-sized case series and cross-sectional studies considering limited co-variables. MATERIALS AND METHODS: Data from two USA national health surveys [NHIS 2014-2017 and NHANES 2005-2018] were analyzed using multinomial logistic regression to study the impact of type of edentulism and number of remaining teeth on memory and concentration problems. Age, gender, socioeconomic status, education level, cardiovascular health index, body mass index, exercise, alcohol, smoking habits, and anxiety and depression were used as covariates. RESULTS: The combined population sample was 102,291 individuals. Age, socioeconomic status, educational level, anxiety and depression levels, and edentulism showed the highest odds ratios for cognitive decline. Number of teeth present in the mouth was found to be a predictor of cognitive status. This association showed a gradient effect, so that the lower the number of teeth, the greater the risk of exhibiting cognitive decline. CONCLUSIONS: Edentulism was found among the higher ORs for cognitive impairment. CLINICAL RELEVANCE: Maintenance of functional teeth through the promotion of oral health may contribute to the preservation of memory/concentration and other essential cognitive functions. Thus, increasing and efficiently coordinating efforts aimed at preventing of tooth loss in the adult population could substantially contribute to reduce the incidence of cognitive impairment.

Expression of Musashi-1 Increases in Bone Healing.

Musashi-1 (MSI1) is an RNA-binding protein that regulates progenitor cells in adult and developing organisms to maintain self-renewal capacities. The role of musashi-1 in the bone healing environment and its relation with other osteogenic factors is unknown. In the current study, we analyze the expression of MSI1 in an experimental model of rat femoral bone fractures. We also analyze the relation between MSI1 expression and the expression of two osteogenic markers: periostin (POSTN) and runt-related transcription factor 2 (RUNX2). We use histological, immunohistochemical, and qPCR techniques to evaluate bone healing and the expression of MSI1, POSTN, and RUNX2 over time (4, 7, and 14 days). We compare our findings with non-fractured controls. We find that in bone calluses, the number of cells expressing MSI1 and RUNX2 increase over time and the intensity of POSTN expression decreases over time. Within bone calluses, we find the presence of MSI1 expression in mesenchymal stromal cells, osteoblasts, and osteocytes but not in hypertrophic chondrocytes. After 14 days, the expression of MSI1, POSTN, and RUNX2 was significantly correlated. Thus, we conclude that musashi-1 potentially serves in the osteogenic differentiation of mesenchymal stromal cells and bone healing. Therefore, further studies are needed to determine the possibility of musashi-1's role as a clinical biomarker of bone healing and therapeutic agent for bone regeneration.

Growth Factors in Oral Tissue Engineering: New Perspectives and Current Therapeutic Options.

The present investigation is aimed at systematically analyzing the recent literature about the innovative scaffold involved in the reconstructive surgeries by applying growth factors and tissue engineering. An extensive review of the contemporary literature was conducted according to the PRISMA guidelines by accessing the PubMed, Embase, and Scopus Elsevier databases. Authors performed the English language manuscript research published from 2003 to 2020. A total of 13 relevant studies were included in the present review. The present systematic review included only papers with significant results about correlation between scaffold, molecular features of growth factor, and reconstructive surgeries in oral maxillofacial district. The initial research with filters recorded about 1023 published papers. Beyond reading and considering of suitability, only 42 and then 36 full-text papers were recorded for the revision. All the researches recorded the possibility of using growth factors on rebuilding atrophic jaws. Different growth factors like morphogenetic factors, cytokines, and inflammatory ones and their application over different scaffold materials were recorded. Further investigations should be required in order to state scientific evidence about a clear advantage of applying tissue engineering for therapeutic purpose.

Three-dimensional analysis of dimensional changes after alveolar ridge preservation with bone substitutes or plasma rich in growth factors: Randomized and controlled clinical trial.

OBJECTIVES: To evaluate alveolar ridge dimensional changes of different alveolar ridge preservation techniques after 3 months of tooth extraction and to compare the efficacy of autologous plasma rich in growth factor (PRGF) to the bone substitutes in alveolar ridge preservation and sites left to heal spontaneously. MATERIALS AND METHODS: Forty patients requiring tooth extraction in the anterior maxilla were randomly allocated to the four following treatment modalities: spontaneous healing (control), natural bovine bone mineral covered with resorbable native collagen membrane (BBM/CM), freeze-dried bone allograft covered with resorbable native collagen membrane (FDBA/CM) and PRGF alone. Cone beam computed tomography (CBCT) scans were taken after surgery and 3 months later. The measurements of height and width (at 1, 3, and 5 mm below the crest) were performed after superimposing the 2 consecutive CBCT scans. RESULTS: The greatest horizontal alveolar bone resorption at 1 mm below bone crest was observed in the control group (-1.61 ± 1.76 mm, P = .037), whereas the least reduction in width was found in the BBM/CM group (-0.68 ± 0.67 mm, P = .037). The most pronounced alveolar height reduction was observed in the control group (-0.86 ± 0.43 mm), whereas alveolar ridge preservation with BBMC/CM (-0.26 ± 0.91 mm) and PRGF (-0.54 ± 0.86 mm) successfully reduced the alveolar height reduction as compared to the control group. CONCLUSIONS: Alveolar ridge preservation technique in the esthetic zone using BBM/CM or using PRGF is beneficial to reduce horizontal and vertical bone changes.

On the Relationship Between White Matter Structure and Subjective Pain. Lessons From an Acute Surgical Pain Model.

Background: Pain has been associated with structural changes of the brain. However, evidence regarding white matter changes in response to acute pain protocols is still scarce. In the present study, we assess the existence of differences in brain white matter related to pain intensity reported by patients undergoing surgical removal of a mandibular impacted third molar using diffusion tensor imaging (DTI) analysis. Methods: 30 participants reported their subjective pain using a visual analog scale at three postsurgical stages: under anesthesia, in pain, and after the administration of an analgesic. The diffusion data were acquired prior to surgery. Results: DTI analysis yielded significant positive associations of fractional anisotropy in white matter areas related to pain processing (corticospinal tract, corona radiata, corpus callosum) with the differences in pain between the three postsurgery stages. Extent and location of these associations depended on the magnitude of the subjective pain differences. Tractography analysis indicated that some pain-tract associations are significant only when pain stage is involved in the contrast (posterior corona radiata), while others (middle cerebellar peduncle, pontine crossing) are only when anesthesia is involved in the contrast. Conclusions: The association of white matter fractional anisotropy and connectivity, measured before the pain stages, with subjective pain depends on the magnitude of the differences in pain scores.

Piezoelectric bone surgery compared with conventional rotary instruments in oral surgery and implantology: Summary and consensus statements of the International Piezoelectric Surgery Academy Consensus Conference 2019.

PURPOSE: Piezoelectric bone surgery was introduced into clinical practice almost 20 years ago as an alternative method for cutting bone in dental surgical procedures, in an attempt to reduce the disadvantages of using conventional rotary instruments. The aim of this Consensus Conference was to evaluate the current evidence concerning the use of piezoelectric surgery in oral surgery and implantology. MATERIALS AND METHODS: Three working groups conducted three meta-analyses with trial sequential analysis, focusing on the use of piezoelectric surgery in impacted mandibular third molar extraction, lateral sinus floor elevation and implant site preparation. The method of preparation of the systematic reviews, based on comprehensive search strategies and following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, was discussed and standardised. RESULTS: Moderate/low evidence suggests that piezoelectric surgery is significantly associated with a more favourable postoperative course (less pain, less trismus) after impacted mandibular third molar extraction than conventional rotary instruments. Moderate evidence suggests that implants inserted with piezoelectric surgery showed improved secondary stability during the early phases of healing compared with those inserted using a drilling technique. Strong/moderate evidence suggests that piezoelectric surgery prolongs the duration of surgery in impacted mandibular third molar extraction, sinus floor elevation and implant site preparation, but it is unclear whether the slight differences in duration of surgery, even if statistically significant, represent a real clinical advantage for either operator or patient. Weak evidence or insufficient data are present to draw definitive conclusions on the other investigated outcomes. CONCLUSIONS: Further well-designed trials are needed to fully evaluate the effects of piezoelectric surgery, especially in implant site preparation and sinus floor elevation.

Osseointegration around dental implants biofunctionalized with TGFß-1 inhibitor peptides: an in vivo study in beagle dogs.

The aim of this study was to evaluate the effect of biofunctionalization with two TGF-ß1 inhibitor peptides, P17 and P144, on osseointegration of CP-Ti dental implants. A total of 36 implants (VEGA, Klockner®) with 3.5 × 8 mm internal connection were used in this study, divided in three groups: (1) control group (n = 12), (2) implants which surfaces were biofunctionalized with P17 peptide inhibitor (n = 12), (3) implants with surfaces biofunctionalized by P144 peptide (n = 12). Three implants, one from each group, were inserted in both hemimandibles of 6 beagle dogs, 2 months after tooth extraction. Two animals were sacrificed at 2, 4 and 8 weeks post implant insertion, respectively. The samples were analyzed by Backscattering Scanning Electron Microscopy (BS-SEM) and histological analysis. Histomorphometric analysis of bone to implant contact (BIC), peri-implant bone fraction (BF) and interthread bone (IB) were carried out. Bone formation around implants measured by quantitative analysis, BS-SEM, was significantly higher in the P17-biofunctionalized implants, 4 and 8 weeks after the implantation. Histomorphometric analysis of BIC, BF and IB showed higher values in the P17-biofunctionalized group at initial stages of healing (2 weeks) and early osseointegration both at 4 and 8 weeks. For P144 biofunctionalized implants, the histomorphometric values obtained are also higher than control group. Accordingly, better results in the experimental groups were proven both by the quantitative and the qualitative analysis. Surface biofunctionalization with TGF-ß1 inhibitor peptides, P17 and P144, resulted in better quantitative and qualitative parameters relative to implant osseointegration.

Exosome: A New Player in Translational Nanomedicine.

Exosomes are extracellular vesicles released by the vast majority of cell types both in vivo and ex vivo, upon the fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. Two main functions have been attributed to exosomes: their capacity to transport proteins, lipids and nucleic acids between cells and organs, as well as their potential to act as natural intercellular communicators in normal biological processes and in pathologies. From a clinical perspective, the majority of applications use exosomes as biomarkers of disease. A new approach uses exosomes as biologically active carriers to provide a platform for the enhanced delivery of cargo in vivo. One of the major limitations in developing exosome-based therapies is the difficulty of producing sufficient amounts of safe and efficient exosomes. The identification of potential proteins involved in exosome biogenesis is expected to directly cause a deliberate increase in exosome production. In this review, we summarize the current state of knowledge regarding exosomes, with particular emphasis on their structural features, biosynthesis pathways, production techniques and potential clinical applications.