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Abstract This joint report from the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP) aims for a consensus around the scientific rationale and clinical strategy for the management of osteoporotic patients affected by periodontitis who are undergoing anti-resorptive (AR) therapy to manage the risk of the occurrence of a medication-related osteonecrosis of the jaws (MRONJ). Osteoporosis and periodontitis are chronic diseases with a high prevalence in aging patients, and they share some of the same pathogenetic mechanisms based upon inflammation. Available evidence shows the relationship among osteoporosis, AR agents, periodontitis and implant therapy in relation to the incidence of MRONJ. Uncontrolled periodontitis may lead to tooth loss and to the need to replace teeth with dental implants. Tooth extraction and surgical dental procedures are recognized as the main risk factors for developing MRONJ in individuals taking AR therapy for osteometabolic conditions. Although the incidence of MRONJ in osteometabolic patients taking AR therapy may be as low as 0.9%, the increasing prevalence of osteoporosis and the high prevalence of periodontitis suggest that this potential complication should not be overlooked. Good clinical practice (GCP) guidelines are proposed that aim at a more integrated approach (prescriber, dentist, periodontist and dental hygienist) in the management of periodontitis patients undergoing AR therapy for osteometabolic disorders to reduce the risk of MRONJ. Dental professional and prescribers should educate patients regarding the potential risk associated with the long-term use of AR therapy and oral health behavior.

This joint report from the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP) aims for a consensus around the scientific rationale and clinical strategy for the management of osteoporotic patients affected by periodontitis who are undergoing anti-resorptive (AR) therapy to manage the risk of the occurrence of a medication-related osteonecrosis of the jaws (MRONJ). Osteoporosis and periodontitis are chronic diseases with a high prevalence in aging patients, and they share some of the same pathogenetic mechanisms based upon inflammation. Available evidence shows the relationship among osteoporosis, AR agents, periodontitis and implant therapy in relation to the incidence of MRONJ. Uncontrolled periodontitis may lead to tooth loss and to the need to replace teeth with dental implants. Tooth extraction and surgical dental procedures are recognized as the main risk factors for developing MRONJ in individuals taking AR therapy for osteometabolic conditions. Although the incidence of MRONJ in osteometabolic patients taking AR therapy may be as low as 0.9%, the increasing prevalence of osteoporosis and the high prevalence of periodontitis suggest that this potential complication should not be overlooked. Good clinical practice (GCP) guidelines are proposed that aim at a more integrated approach (prescriber, dentist, periodontist and dental hygienist) in the management of periodontitis patients undergoing AR therapy for osteometabolic disorders to reduce the risk of MRONJ. Dental professional and prescribers should educate patients regarding the potential risk associated with the long-term use of AR therapy and oral health behavior., (© 2023. The Author(s).)

Purpose: Osteoradionecrosis (ORN) of the jaw is a severe and debilitating complication of the head and neck radiotherapy which frequently occurrs after oral surgery. This clinical audit aims aevaluate the effectiveness of combined use of pentoxifylline and tocopherol (PENTO) in prevention ORN onset in patient who underwent oral surgery after head and neck radiotherapy (RT)., Material Method: In this clinical audit Pentoxifylline 400 mg, twice a day, and Tocopherol 800 IU once a day (PENTO protocol) have been prescribed. Patients started the protocol 1 week before the surgical procedure and continued for 8 weeks after., Results: Twenty-nine patients were included. They received 75 surgical interventions under PENTO protocol: 71 surgical procedures of dental extraction (single or multiple dental extractions in each session) and four implant placements. A total of 152 dental extractions were carried out: 64 surgical extractions which required the raising of mucoperiosteal flap, and 88 simple extractions. Four out of 29 patients developed ORN after surgical procedures: four cases of ORN occurred after dental extractions (5.6%) and one case of ORN after implant placement (25%)., Conclusion: PENTO is a useful ORN preventive protocol, low-cost and clinically feasible, safe and well tolerated by patients. Further studies should focus on better defining the effectiveness PENTO, independently from the antibiotic therapy., (© 2022 The Authors. Special Care in Dentistry published by Special Care Dentistry Association and Wiley Periodicals LLC.)

Background: Chronic trauma of oral mucosa, resulting from repeated and persistent mechanical irritative action of an intraoral injury agent, has repeatedly been reported to be possibly implicated in the development of oral squamous cell carcinoma (OSCC)., Objectives: The present systematic review aimed to assess whether chronic mechanical trauma can be considered a risk factor for OSCC., Data Sources: PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus; EMBASE, Web of Science., Study Eligibility Criteria: Cohort studies comparing OSCC incidence among subjects with/without chronic mechanical trauma or case-control or cross-sectional studies comparing chronic mechanical trauma among subjects with/without OSCC., Results: Only one prospective case-control study fulfilled the inclusion criteria, but the quality of the evidence provided is not enough to define trauma as a risk factor for OSCC. The main limitation is the presence of only one case-control study at high risk of bias. In the absence of strong evidence supporting the role of trauma in OSCC, a thorough discussion on trauma and carcinogenesis has been performed., Conclusions: Available evidence does not support an active role for chronic trauma in oral carcinogenesis, neither as promoter nor as progressor factor. Prospective cohort studies able to better assess trauma in OSCC are needed., (© 2021 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

The development of opportunistic pathogenic Candida strains insensitive to several classes of antifungals has emerged as a major health care problem during the last years. Combinational therapy of natural products (e.g., essential oils, EOs) with conventional antifungals has been suggested as a promising alternative to overcome this medical problem. The present study investigates the potential antifungal activity of EOs extracted from some selected medicinal plants, alone and in combination with two common conventional antifungals (fluconazole and amphotericin B) against four clinical Candida isolates. MIC assays indicated that EOs induced strong anticandidal activities with MIC values ranging from 0.162 to 4.950 mg/mL. The combination of amphotericin B with Thymus leptobotrys , Origanum compactum and Artemisia herba alba EOs provided a synergistic effect against C. krusei only, with MIC gain of four-fold, and additive effect against remaining strains (MIC gain = two-fold). Interesting synergistic interactions were observed by combining all studied EOs with fluconazole, with reduction rates of their MICs ranging from 16 to 512-fold. This synergistic effect was very pronounced with the combination of T. leptobotrys EO and fluconazole. These findings indicate that studied EOs can be used as anti-candidals in combination with antifungals, particularly fluconazole, to counteract the emergence of resistant Candida spp.

Objective: The World Workshop on Oral Medicine VII chose the oral microbiome as a focus area. Part 1 presents the methodological state of the science for oral microbiome studies. Part 2 was guided by the question: What is currently known about the microbiome associated with oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa?, Materials and Methods: A scoping review methodology was followed to identify and analyse relevant studies on the composition and potential functions of the oral microbiota using high-throughput sequencing techniques. The authors performed searches in PubMed and EMBASE. After removal of duplicates, a total of 239 potentially studies were identified., Results: Twenty-three studies on oral squamous cell carcinoma, two on oral leukoplakia and four on oral lichen planus were included with substantial differences in diagnostic criteria, sample type, region sequenced and sequencing method utilised. The majority of studies focused on bacterial identification and recorded statistically significant differences in the oral microbiota associated with health and disease. However, even when comparing studies of similar methodology, the microbial differences between health and disease varied considerably. No consensus on the composition of the microbiomes associated with these conditions on genus and species level could be obtained. Six studies on oral squamous cell carcinoma had included in silico predicted microbial functions (genes and/or pathways) and found some similarities between the studies., Conclusions: Attempts to reveal the microbiome associated with oral mucosal diseases are still in its infancy, and the studies demonstrate significant clinical and methodological heterogeneity across disease categories. The immense richness and diversity of the microbiota clearly illustrate that there is a need for additional methodologically comparable studies utilising deep sequencing approaches in significant cohorts of subjects together with functional analyses. Our hope is that following the recipe as outlined in our preceding companion paper, that is Part 1, will enhance achieving this in the future and elucidate the role of the oral microbiome in oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Teeth and the periodontal tissues represent a highly specialized functional system. When periodontal disease occurs, the periodontal complex, composed by alveolar bone, root cementum, periodontal ligament, and gingiva, can be lost. Periodontal regenerative medicine aims at recovering damaged periodontal tissues and their functions by different means, including the interaction of bioactive molecules, cells, and scaffolds. The application of growth factors, in particular, into periodontal defects has shown encouraging effects, driving the wound healing toward the full, multi-tissue periodontal regeneration, in a precise temporal and spatial order. The aim of the present comprehensive review is to update the state of the art concerning tissue engineering in periodontology, focusing on biological mediators and gene therapy.

The primary outcome of the present study was to assess the percentage of pocket closure, and the secondary aim was to evaluate the clinical performance in terms of clinical attachment level (CAL) gain, probing pocket depth (PPD) reduction, and gingival recession (REC) after the use of cavitron ultrasonic surgical aspirator (CUSA) in deep infrabony defects. Fourteen deep infrabony defects in 11 patients who were previously treated with active periodontal therapy followed by one year of supportive periodontal therapy (at least three sessions) were additionally treated by the aid of CUSA. Eighty-six percent of the initial defects (12 out of 14) resulted in a PD < 5 mm, showing complete resolution six months after CUSA treatment, without any adverse event and with negligible pain (VAS from 0 to 3). CUSA showed potential as a method to promote pocket healing, reduce PPD, and increase clinical attachment ( P < 0.001) in deep infrabony defects. This trial is registered with ClinicalTrials.gov NCT03567161.

Objectives: To investigate the quality of sleep and the psychological profiles of a large cohort of Italian patients with burning mouth syndrome (BMS) and to clarify the relationships between these variables and pain., Methods: In this case-control study, 200 patients with BMS vs an equal number of age- and sex-matched healthy controls, recruited in 10 universities, were enrolled. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Numeric Pain Intensity Scale (NRS) and Total Pain Rating Index (T-PRI) were administered. Descriptive statistics, including the Mann-Whitney U test and hierarchical multiple linear regression analysis, were used., Results: Poor sleep quality (PSQI ≥ 5) was present in 78.8% (160) patients with BMS. BMS patients had statistically higher scores in all items of the PSQI and ESS than the healthy controls (p < .001). A depressed mood and anxiety correlated positively with sleep disturbance. The Pearson correlations were 0.570 for the PSQI vs HAM-D (p < .001) and 0.549 for the PSQI vs HAM-A (p < .001). Pain intensity (NRS) poorly correlated to sleep quality; the Pearson correlation was 0.162 for the PSQI vs NRS (p = .021)., Conclusions: The BMS patients showed a poor sleep quality, anxiety and depression, as compared with the controls, highlighting the relationships between oral burning, sleep and mood., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Impacted maxillary canine teeth commonly occur in the general population. The traditional therapeutic approach comprises fenestration and orthodontic traction; however, if traction is not feasible or the patient refuses orthodontic treatment, an alternative solution is to remove the impacted tooth and immediately place an implant. This technical note describes a novel surgical approach to rehabilitation after impacted canine tooth removal, entailing immediate placement of a long implant in combination with regenerative materials and a barrier. Of note, this procedure preserves the apical ridge bone crest, allowing implant anchorage and primary stability to be achieved.

Dental implant prostheses cannot preclude a correct and stable implant osseointegration, which is still a challenge and greatly depends on biomaterial-cell interface. Titanium (Ti) coating using polyelectrolyte poly-L-lysine (PLL) may represent an interesting and simple approach, to provide a charged surface net able to improve cell adherence. However, in vitro and in vivo effects of Ti coated with PLL have been poorly investigated. The aims of the present study are (1) to obtain and characterize, chemically and physically, Ti disks coated with PLL (TiPLL); (2) to perform in vitro studies on osteoblast cell lines' cytocompatibility and functionality (alkaline phosphatase [ALP] activity, calcium deposition, proinflammatory interleukin 6 production); (3) to obtain in vivo evidence of osseointegration, using a sheep animal model. XPS, AFM, and contact-angle analyses demonstrated that the Ti disk was successfully covered with PLL, providing higher hydrophilicity to the Ti disk. No cellular toxicity, enhanced calcium deposition, and a decreased tendency toward interleukin-6 production were observed in the osteoblast seeded onto TiPLL. In vivo experiments showed cortical bone microhardness at 3 months significantly improved in the presence of the PLL coating. PLL coating on Ti implants seemed to safely enhance calcium deposition and implant early osseointegration in animals, suggesting promising evidence to optimize the surface properties of dental implants.

Objectives: To assess the current scope and status of Oral Medicine-specific software (OMSS) utilized to support clinical care, research, and education in Oral Medicine and to propose a strategy for broader implementation of OMSS within the global Oral Medicine community., Study Design: An invitation letter explaining the objectives was sent to the global Oral Medicine community. Respondents were interviewed to obtain information about different aspects of OMSS functionality., Results: Ten OMSS tools were identified. Four were being used for clinical care, one was being used for research, two were being used for education, and three were multipurpose. Clinical software was being utilized as databases developed to integrate of different type of clinical information. Research software was designed to facilitate multicenter research. Educational software represented interactive, case-orientated technology designed for clinical training in Oral Medicine. Easy access to patient data was the most commonly reported advantage. Difficulty of use and poor integration with other software was the most commonly reported disadvantage., Conclusions: The OMSS presented in this paper demonstrate how information technology (IT) can have an impact on the quality of patient care, research, and education in the field of Oral Medicine. A strategy for broader implementation of OMSS is proposed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Extensive skin loss and chronic wounds are still a significant challenge to clinicians: even if injured epidermis is normally able to self-renew, deep injuries can cause negative regulation of the wound healing cascade, leading to chronic wound formation. Skin-autografting surgical procedures are often limited by the poor availability of healthy tissue, whereas the use of non-self-tissues for allografts presents some severe risks. Tissue-engineered skin substitutes have recently become viable as a suitable alternative to auto- and allografts. However, biologists, biochemists, and technical engineers are still struggling to produce complex skin substitutes that can readily be transplanted in large quantities. The ambitious goal is now to construct a dermoepidermal substitute that rapidly vascularizes and optimally supports a stratifying epidermal graft on a biodegradable matrix. This review analyzes these aspects in light of the available literature and the authors' experience.

Burning mouth syndrome (BMS) is a chronic condition most common in middle-aged and elderly women, with prevalence rates in the general population ranging from 0.5% to 5%. Defined by the International Headache Society as "an intraoral burning sensation for which no medical or dental cause can be found," BMS is considered a form of neuropathic pain. The management of BMS remains unsatisfactory. In this pilot study, we investigated the use of acupuncture in a small group of BMS patients. The study group, after 4 refusals, was composed of 10 BMS patients (9 females and 1 male; mean age, 65.2 years; range, from 48 to 80 years; mean duration of BMS, 2.6 years; SD ± 0.8 years). Oral pain/burning sensation (primary outcome) was measured using a visual analogue scale (VAS). Health-related quality of life (secondary outcome) was measured using the 36-item Short-Form Health Survey (SF-36). Acupuncture treatment lasted 8 weeks and consisted of 20 sessions. Patients reported a mean reduction in pain of 0.99 points on the VAS (max 2.1-min 0.1), which, although slight, was statistically significant (Wilcoxon test P < 0.009). No significant improvement in the overall score for quality of life was observed, although subjects receiving acupuncture treatment seemed better able cope with their oral symptoms., (© 2013 The Authors Pain Practice © 2013 World Institute of Pain.)

Tissue homeostasis depends closely on the activity and welfare of adult stem cells. These cells represent a promising tool for biomedical research since they can aid in treatment and promote the regeneration of damaged organs in many human disorders. Adult stem cells indefinitely preserve their ability to self-renew and differentiate into various phenotypes; this capacity could be promoted in vitro by particular culture conditions (differentiation media) or spontaneously induced in vivo by exploiting the biochemical and mechanical properties of the tissue in which the stem cells are implanted. Among the different sources of adult stem cells, adipose tissue is an attractive possibility thanks to its ready availability and the standard extraction techniques at our disposal today. This review discusses the isolation, characterization, and differentiation of human adipose-derived adult stem cells, as well as regeneration strategies, therapeutic uses, and adverse effects of their delivery. In particular, since oral disorders (e.g., trauma, erosion, and chronic periodontitis) often cause the loss of dental tissue along with functional, phonetic, and aesthetic impairment, this review focuses on the application of human adipose-derived adult stem cells, alone or in combination with biomaterials, in treating oral diseases.

Chlorhexidine (CHX) is one of the most commonly prescribed antiseptic agents in the dental field. It has a long-lasting antibacterial activity with a broad-spectrum of action and it has been shown to reduce plaque, gingival inflammation and bleeding. Its use is considered a powerful adjuvant to mechanical oral hygiene (brushing and flossing), especially in those cases in which it cannot be performed correctly. Available as mouthwash, gel, aerosol, spray and disks, CHX is considered a safe compound, with minimal and transitory local and systemic side effects. Data support its periodic use as an adjuvant to normal brushing and flossing in subjects unable to maintain proper oral hygiene due to physical and/or mental impairment, or lack of motivation, or decreased salivary rate. CHX is also a useful alternative to mechanical oral hygiene procedures in those cases in which they are contraindicated, e.g. after a surgical procedure, or as a preoperative rinse before procedures in which use of a dental dam is not possible. The aim of this article is to offer a complete review of literature regarding the characteristics, the applications and the problems associated with the use of chlorhexidine in the dental field.

Inorganic nanosized drug carriers are a promising field in nanomedicine applied to cancer. Their conjugation with antibodies combines the properties of the nanoparticles themselves with the specific and selective recognition ability of the antibodies to antigens. Biomimetic carbonate-hydroxyapatite (HA) nanoparticles were synthesized and fully characterized; human IgGs, used as model antibodies, were coupled to these nanocrystals. The maximum loading amount, the interaction modelling, the preferential orientation and the secondary structure modifications were evaluated using theoretical models (Langmuir, Freundlich and Langmuir-Freundlich) spectroscopic (UV-Vis, Raman), calorimetric (TGA), and immunochemical techniques (ELISA, Western Blot). HA nanoparticles of about 30 nm adsorbed human IgGs, in a dose-dependent, saturable and stable manner with micromolar affinity and adsorption capability around 2.3 mg/m(2). Adsorption isotherm could be described by Langmuir-Freundlich model, and was due to both energetically homogeneous and heterogeneous binding sites on HA surface, mainly of electrostatic nature. Binding did not induce secondary structure modification of IgGs. A preferential IgG end-on orientation with the involvement of IgG Fc moiety in the adsorption seems most probable due to the steric hindrance of their Fab domains. Biomimetic HA nanocrystals are suitable substrates to produce nanoparticles which can be functionalized with antibodies for efficient targeted drug delivery to tumours., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Maxillofacial, orthopedic, oral, and plastic surgery require materials for tissue augmentation, guided regeneration, and tissue engineering approaches. In this study, the aim was to develop and characterize a new extrudable hydrogel, based on agarose gel (AG; 1.5% wt) and to evaluate the local effects after subcutaneous implantation in comparison with collagen and hyaluronic acid. AG chemical-physical properties were ascertained through Fourier transform infrared (FT-IR) spectroscopy and rheological analysis. In vivo subcutaneous implants were performed, and histological and histomorphometric evaluations were done at 1, 4, 12, and 16 weeks. FT-IR confirmed that spectroscopic properties were the same for the baseline agarose and rheological characterization established that AG is a weak hydrogel. Subcutaneous AG implants induced new vessels and fibrous tissue formation rich in neutrophils; the capsule thickness around AG increased until the 12th week but remained thinner than those around hyaluronic acid and collagen. At 16 weeks, the thickness of the capsule significantly decreased around all materials. This study confirmed that 1.5% wt AG possesses some of the most important features of the ideal biocompatible material: safety, effectiveness, costless, and easily obtained with specific chemical and geometrical characters; the AG can represent a finely controllable and biodegradable polymeric system for cells and drug delivery applications.

The use of biomaterials in dentistry is more widespread than in any other medical field in terms of both amount and variety. Most of them were not originally designed for dental applications but for other medical applications or, sometimes, for no medical purposes. Among these materials, biodegradable materials play an important role, especially in bone regeneration and in periodontal surgery. This paper briefly reviews some degradable polymers developed as tools for the treatment of periodontal and bone diseases. We discuss materials previously applied in other industrials contexts, such as polyesters, methylcellulose, and chitosan and we provide perspectives for their use in periodontal regeneration.

Two kinds of hydroxyapatite (HA) crystals were studied as subcutaneous fillers in order to evaluate how their different degree of crystallinity and dimensions influence in vivo resorption. By appropriately adjusting the synthesis temperature, poorly crystalline HA (HApc) and highly crystalline HA (HAhc) were synthesized into clusters of needle-shaped crystals of about 50 nm and plate-shaped crystals of about 100 nm, respectively. The clusters of HApc had larger dimensions (30 µm) than those of HAhc (3 µm). Subcutaneous in vivo inoculations were performed in ten 6-month-old FVB female mice. HAhc underwent complete macroscopic resorption already 4 weeks after the implantation while HApc still showed agglomerates at the eighth week. This unexpected finding may be ascribed to the different size and morphology of the HAhc nanocrystals responsible for a lower aggregation and microcluster dimension than HApc nanocrystals.