Publications by authors named "Giacomo Oteri"

49 Publications

Clinical validation of 13-gene DNA methylation analysis in oral brushing samples for detection of oral carcinoma: An Italian multicenter study.

Head Neck 2021 Jan 28. Epub 2021 Jan 28.

Department of Biomedical and Neuromotor Sciences, Section of Oral Sciences, University of Bologna, Bologna, Italy.

Background: The aim of this Italian multicenter study was to evaluate the diagnostic performance of a minimally invasive method for the detection of oral squamous cell carcinoma (OSCC) based on 13-gene DNA methylation analysis in oral brushing samples.

Methods: Oral brushing specimens were collected in 11 oral medicine centers across Italy. Twenty brushing specimens were collected by each center, 10 from patients with OSCC, and 10 from healthy volunteers. DNA methylation analysis was performed in blindness, and each sample was determined as positive or negative based on a predefined cutoff value.

Results: DNA amplification failed in 4 of 220 (1.8%) samples. Of the specimens derived from patients with OSCC, 93.6% (103/110) were detected as positive, and 84.9% (90/106) of the samples from healthy volunteers were negative.

Conclusion: These data confirmed the diagnostic performance of our novel procedure in a large cohort of brushing specimens collected from 11 different centers and analyzed in blindness.
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http://dx.doi.org/10.1002/hed.26624DOI Listing
January 2021

Medication-Related Osteonecrosis of the Jaws and CDK4/6 Inhibitors: A Recent Association.

Int J Environ Res Public Health 2020 12 18;17(24). Epub 2020 Dec 18.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98122 Messina, Italy.

The purpose of the present study was to estimate the prevalence of cyclin-dependent kinase (CDK) 4/6 inhibitors use among cancer patients from the medication-related osteonecrosis of the jaw (MRONJ) cohort of the University of Messina. We retrospectively reviewed the records of all patients with either intravenous bisphosphonates or denosumab-related MRONJ reported in the electronic health records of the Unit of Oral Surgery, School of Dentistry, University of Messina between the first quarter of 2018 and the first quarter 2020 to identify eligible patients. We observed six cases of MRONJ associated with CDK4/6 inhibitors concomitantly with intravenous bisphosphonates and/or denosumab in breast cancer patients. The CDK4/6 inhibitors registered were palbociclib (n = 5) and abemaciclib (n = 1). Data of cancer patients diagnosed with MRONJ in the same period (n = 10) were extracted for comparison. The comparative assessment with this group of patients showed a similar distribution of MRONJ stage ranged and clinical course after treatment. The degree of risk for osteonecrosis in patients taking these new classes of drugs is uncertain but warrants awareness and close monitoring. The role of premedication dental evaluation as a prevention strategy has been acknowledged for cancer patients about to initiate intravenous bisphosphonates and/or denosumab for treatment of bone metastasis, but additional attention should be paid to whom are assuming CDK4/6 inhibitors because of their oral adverse events.
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http://dx.doi.org/10.3390/ijerph17249509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767118PMC
December 2020

Comparison between Additive and Subtractive CAD-CAM Technique to Produce Orthognathic Surgical Splints: A Personalized Approach.

J Pers Med 2020 Dec 11;10(4). Epub 2020 Dec 11.

Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via S. Sofia 78, 95124 Catania, Italy.

The present study aimed to evaluate the accuracy of digitally designed surgical splints generated with milling technology (material subtractive procedure) and with 3D printing technology (material additive procedure) through a customized approach in the planning of surgical orthognathic splints. Cone beam computed tomography (CBCT) examinations and scanned dental models of 10 subjects who had required surgical treatment of skeletal malocclusion were included. Simulation of the orthognathic surgery was performed according to dento-skeletal and aesthetic characteristics of the subjects and the visual treatment objective (VTO), using Dolphin3D software (Dolphin Imaging, version 11.0, Chatsworth, CA, USA). Afterward, the Appliance Designer software (3Shape A/S, Copenhagen, Denmark) was used to digitally design the surgical splints that were generated twice using laser stereolithography technology (DWS 0.29D, DWS, Vicenza, Italy) and milling technology (Sirona inLab MC X5). Finally, each physical splint was digitalized using a desktop scanner (D500 3D, 3Shape A/S, Copenhagen, Denmark) in order to perform deviation analysis using the original project as a reference. The relative percentage of matching (trueness) was calculated (Geomagic Control X software (3D Systems, version 2018.1.1, 3D Systems, Rock Hill, SC, USA). An Independent Student's -test was used to statistically analyze the data. The milled splints showed a lower value of root to mean square (RMS) relative to the original project (0.20 mm ± 0.018) compared to the prototyped splints (0.31 ± 0.021) ( < 0.001). According to the present findings, surgical splints generated with milling technology present higher trueness compared with 3D printing technology.
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http://dx.doi.org/10.3390/jpm10040273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768501PMC
December 2020

Preclinical and Clinical Applications of Biomaterials in the Enhancement of Wound Healing in Oral Surgery: An Overview of the Available Reviews.

Pharmaceutics 2020 Oct 24;12(11). Epub 2020 Oct 24.

Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, Via C. Valeria, 98125 Messina, Italy.

Oral surgery has undergone dramatic developments in recent years due to the use of biomaterials. The aim of the present review is to provide a general overview of the current biomaterials used in oral surgery and to comprehensively outline their impact on post-operative wound healing. A search in Medline was performed, including hand searching. Combinations of searching terms and several criteria were applied for study identification, selection, and inclusion. The literature was searched for reviews published up to July 2020. Reviews evaluating the clinical and histological effects of biomaterials on post-operative wound healing in oral surgical procedures were included. Review selection was performed by two independent reviewers. Disagreements were resolved by a third reviewer, and 41 reviews were included in the final selection. The selected papers covered a wide range of biomaterials such as stem cells, bone grafts, and growth factors. Bioengineering and biomaterials development represent one of the most promising perspectives for the future of oral surgery. In particular, stem cells and growth factors are polarizing the focus of this ever-evolving field, continuously improving standard surgical techniques, and granting access to new approaches.
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http://dx.doi.org/10.3390/pharmaceutics12111018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692581PMC
October 2020

Finite Element Method and Von Mises Investigation on Bone Response to Dynamic Stress with a Novel Conical Dental Implant Connection.

Biomed Res Int 2020 7;2020:2976067. Epub 2020 Oct 7.

Department of Biomedical and Dental Sciences, Morphological and Functional Images, University of Messina, Policlinico G. Martino, Via Consolare Valeria, 98100 Messina, Italy.

The bioengineering and medical and biomedical fields are ever closer, and they manage to obtain surprising results for the development of new devices. The field of simulations and studies in silica has undergone considerable development in recent years, favoring the advancement of medicine. In this manuscript, a study was carried out to evaluate the force distribution on the implant components (In-Kone® Universal) and on the peri-implant tissues subjected to loading. With the finite element analysis and the Von Mises method, it was possible to evaluate this distribution of forces both at 0 degrees (occlusal force) and at 30 degrees; the applied force was 800 N. The obtained results on this new type of connection and on all the implant components are satisfactory; the distribution of forces appears optimal even on the peri-implant tissues. Surely, studies like this help to obtain ever more performing devices, improving both the clinic and the predictability of rehabilitations.
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http://dx.doi.org/10.1155/2020/2976067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568164PMC
October 2020

Medication-Related Osteonecrosis of Jaws (MRONJ) Prevention and Diagnosis: Italian Consensus Update 2020.

Int J Environ Res Public Health 2020 08 18;17(16). Epub 2020 Aug 18.

IAC-ONJ (Italian Allied Committee on ONJ), Temporary Chair at University of Palermo, 90100 Piazza Marina, Italy.

The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference-held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)-after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.
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http://dx.doi.org/10.3390/ijerph17165998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460511PMC
August 2020

Altered Long Noncoding RNA Expression Profile in Multiple Myeloma Patients with Bisphosphonate-Induced Osteonecrosis of the Jaw.

Biomed Res Int 2020 2;2020:9879876. Epub 2020 Jul 2.

Department of Biochemical and Dental Sciences and Morphofunctional Images, University of Messina, Messina, Italy.

Bisphosphonates (BPs) are inhibitors of osteoclast-mediated bone resorption used for the treatment of multiple myeloma (MM) patients with osteolytic lesions. Bisphosphonate-induced osteonecrosis of the jaw (BONJ) is an infrequent drug-caused adverse event of these agents. Long noncoding RNAs (lncRNAs) are a set of more than 200 base pairs, noncoding RNA molecules, which are critical posttranscriptional regulators of gene expression. Our study was aimed at evaluating 17 lncRNAs, whose targets were previously validated as key elements in MM, bone metabolism, and angiogenesis in MM subjects without BONJ (MM group), in MM subjects with BONJ (BONJ group), and a group of healthy controls (CTRL group). Our results demonstrated a different lncRNA profile in BONJ patients compared to MM patients and controls. Two lncRNAs (DANCR and MALAT1) were both downregulated compared to controls and MM, twelve (HOTAIR, MEG3, TP73-AS1, HOTTIP, HIF1A-AS2, MANTIS, CTD-2201E18, CTD1-2003C8, R-471B22, RP1-43E13, RP11-553L6.5, and RP1-286D6) were overexpressed in MM with BONJ, and one (H19) was upregulated compared with only MM. Two lncRNAs (JHDMD1 and MTMR9LP) had higher expression, but these differences were not statistically significant. The examined lncRNAs target several genes and metabolic pathways. An altered lncRNA signature could contribute to the onset of BONJ or have a protective action. Targeting these lncRNAs could offer a possibility for the prevention or therapy of BONJ.
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http://dx.doi.org/10.1155/2020/9879876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354644PMC
July 2020

Oral Surgical Management of Bone and Soft Tissues in MRONJ Treatment: A Decisional Tree.

Life (Basel) 2020 Jun 29;10(7). Epub 2020 Jun 29.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98124 Messina, Italy.

Background: The aim of the present work was to analyze a 10-year retrospective series of surgically treated medication-related osteonecrosis of the jaws (MRONJ) cases, reporting the clinical outcome and success rate for each adopted procedure in order to draw a treatment algorithm that is able to standardize clinical decision making and maximize the success of oral surgical treatment of MRONJ.

Methods: Different surgical approaches were categorized taking into consideration two variables a) hard tissue management (defined as debridement, saucerization or marginal resective surgery of maxillary necrotic bone) and b) soft tissue management (defined as type of flap design and related modality of wound-healing).

Results: For the retrospective cohort study, 103 MRONJ patients were enrolled and a total of 128 surgical procedures were performed. The role of radical-intended surgery using local flaps in MRONJ treatment was investigated, as well as palliative treatments. All stage I-II patients completely healed when a combination of radical necrotic bone surgery associated with a first intention healing of soft tissues was obtained. In stage III, when a patient was not eligible for maxillo-facial surgery, the use of palliative surgical strategies was effective in symptom relief in order to maintain a better quality of life for the duration of the patient's life.

Conclusions: Oral surgery with radical intent associated with a flap design able to ensure first intention healing might represent a valid option for the majority of MRONJ patients. The designed decision tree allows clinicians to assess individual surgical approaches for MRONJ treatment in accordance with patient-centered outcomes and surgical skills.
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http://dx.doi.org/10.3390/life10070099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399969PMC
June 2020

β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors.

Biomedicines 2020 Jun 17;8(6). Epub 2020 Jun 17.

Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy.

Human gingival fibroblasts (GF) and human oral mucosa epithelial cells (EC) with an inflammatory phenotype represent a valuable experimental paradigm to explore the curative activity of agents to be used in oral mucositis. The role of cannabinoid receptor 2 (CB2) has not yet been investigated in oral mucositis. The aim of this study was to evaluate the therapeutic potential of β-Caryophyllene (BCP), a CB2 agonist, in an in vitro model of oral mucositis. GF and EC were stimulated with LPS (2 µg/mL) alone or in combination with BCP; a group of LPS challenged GF and EC were treated with BCP and AM630, a CB2 antagonist. LPS increased the inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-17A whereas it decreased the anti-inflammatory cytokine IL-13. The upstream signals were identified in an augmented expression of NF-κB and STAT-3 and in reduced mRNA levels of PPARγ and PGC-1α. BCP blunted the LPS-induced inflammatory phenotype and this effect was reverted by the CB2 antagonist AM630. These results suggest that CB2 receptors are an interesting target to develop innovative strategies for oral mucositis and point out that BCP exerts a marked curative effect in a preclinical model of oral mucositis which deserves to be confirmed in a clinical setting.
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http://dx.doi.org/10.3390/biomedicines8060164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344807PMC
June 2020

COVID-19 Pandemic and Telephone Triage before Attending Medical Office: Problem or Opportunity?

Medicina (Kaunas) 2020 May 20;56(5). Epub 2020 May 20.

Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, Messina University, 1-98100 Messina, Italy.

During the COVID-19 emergency, the medical operating protocols have been largely modified for reducing any type of contamination risk, for working in a safe way and for making the patient feel in a safe environment. Telemedicine, smart phones and apps could represent important devices for the community, in order to prevent virus trasmission and to perform quick diagnosis and management at medical offices. This manuscript could be useful for clinicians with regard to the current state of the effectiveness of the telephone triage in this COVID-19 epidemic period. Therefore, it could be an important starting point for future perspectives about telemedicine and virtual patient management.
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http://dx.doi.org/10.3390/medicina56050250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279364PMC
May 2020

Dentistry during the COVID-19 Epidemic: An Italian Workflow for the Management of Dental Practice.

Int J Environ Res Public Health 2020 05 11;17(9). Epub 2020 May 11.

Postgraduate School of Oral Surgery, Department of Biomedical, Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy.

The COVID-19 outbreak has raised concerns about infection control all over the world. Among health workers, dentists are particularly exposed to the COVID-19 infection risk. The aim of this paper is to present a workflow to manage dental procedures already in use at the Dental Unit of the University Hospital of Messina. The proposed workflow accounts for the many aspects of dental practitioners' risk in the COVID-19 era, and focuses on the assessment of patient risk level, a two-phase dental procedure management (remote and face-to-face), and the use of specific preventive measures. No cases of COVID-19 infection were detected among patients and staff of the dental unit in a two-month period of time while using this protocol. This workflow seems a promising and effective solution to manage dental procedures during the COVID-19 outbreak, and could be implemented in both public and private practices until the emergency is contained.
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http://dx.doi.org/10.3390/ijerph17093325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246688PMC
May 2020

Role of Local Flaps to Achieve Primary Wound Closure in Medication-Related Osteonecrosis of the Jaws Osseous-Resective Surgery.

J Craniofac Surg 2020 Jun;31(4):e347-e352

Department of Biomedical, Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.

The aim of the present work is to evaluate the most suitable surgical technique in relation to location and extent of medication-related osteonecrosis of the jaws (MRONJ) through comparison of success rate between the routinely used mucoperiostal flaps and different local flaps designs and propose a standardization of surgical procedures according to MRONJ stage and localization with 2 objectives: to provide the surgeon with an algorithm of treatment according to MRONJ localization and extension; to maximize the success of surgical treatment.Thirteen consecutive patients affected by focal MRONJ were surgically treated with radical osteotomy at the Center for Treatment of the Osteonecrosis of the Jaws (University of Messina, Italy).Initial defects were classified according to the classification of the Italian Societies of Oral Medicine and Maxillofacial Surgery (the SICMF-SIPMO staging system) which consider not only bone exposure but also radiological bone involvement. Treatment outcome was retrospectively assessed according to the different adopted surgical procedure: mucoperiostal flaps (GROUP A) advanced mucoperiostal flaps or rotation flaps (GROUP B) local flaps (GROUP C).Outcome after surgical treatment of focal MRONJ was positive in every group irrespective of MRONJ localization and extension. This may be due to the appropriate selection of surgical procedure.The results obtained demonstrated that focal MRONJ surgical treatment is a reliable procedure irrespective of the initial clinical situation. Radical osteotomy combined with appropriate selection of soft tissue management is crucial.
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http://dx.doi.org/10.1097/SCS.0000000000006288DOI Listing
June 2020

Early Diagnosis on Oral and Potentially Oral Malignant Lesions: A Systematic Review on the VELscope Fluorescence Method.

Dent J (Basel) 2019 Sep 4;7(3). Epub 2019 Sep 4.

Multidisciplinary Department of Medical-Surgical and Dental Specialties, Second University of Naples, 34109 Naples, Italy.

The fluorescence method is an innovative technique used by pathologists for examining body mucosa, and for the abnormalities tissue screening, potentially leading to the earlier discovery of pre-cancer, cancer or other disease processes. The early detection is one of the best mechanisms for enabling treatment success, increasing survival rates and maintaining a high quality of life. The purpose of this review is to evaluate the clinical efficiency of this diagnostic tool applied to the oral cavity (VELscope). A literature systematic review has been performed. The initial research provided 53 results after applying the inclusion and exclusion criteria, and after a manual screening of the abstracts by the authors, only 25 results were eligible for review. The results and data contained in all the researches, no older than 10 years, were manually evaluated, and provided useful information on this diagnostic method. The VELscope mean value about sensitivity and specificity resulted of 70.19% and 65.95%, respectively, by results analysis, but despite this some studies disagree about its clinical effectiveness, and this diagnostic method is still much debated in scientific and clinical medical literature. Surely being able to have efficient and effective tools from this point of view could help the clinician in the diagnosis, and also make timelier the pharmacological or surgical therapy, improving the quality of life of the patient, and in some cases guaranteeing a longer survival term.
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http://dx.doi.org/10.3390/dj7030093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784481PMC
September 2019

Role of Antioxidants in Minor Salivary Glands Cancer in the Elderly.

J Craniofac Surg 2019 May/Jun;30(3):823-828

Department of Biomorphology.

Background: Minor salivary gland tumors (MSGTs) are infrequent, representing 10% to 15% of all salivary neoplasms. Despite this low frequency, a significant increase in the incidence of these tumors has been reported in the lasts 30 years. While tumors of the salivary glands can appear at any age, different authors consider the peak of incidence to be associated with old age (60+). The etiopathogenesis of MSGTs remains unclear. In this context, the aim of this study was to explore the hypothesis that age-related changes in salivary antioxidant capacity are involved in the pathogenesis of minor salivary glands tumors to identify possible preventive measures.Furthermore the study aimed to describe the clinico-pathological features of a multi-institutional case series of MSGTs which results are consistent with data in the literature.

Methods: An electronic search of the English language literature was performed using PubMed and Google scholar (). Databases were screened for papers using a number of search strings constructed using relevant terms (minor salivary glands tumors, elderly, diet, antioxidant, saliva, salivary glands).

Results: According to the world literature, the peak of incidence of MSGTs is between the fifth and seventh decades of life. To date, the only confirmed risk factor for salivary gland tumors is the exposure to ionizing radiation. The significantly reduced salivary antioxidant capacity in old people may explain the higher prevalence of these tumors in the elderly population.

Conclusions: Further investigation is required to determine the real etiopathogenesis of MSGTs and why these tumors result more frequent in elderly patients.
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http://dx.doi.org/10.1097/SCS.0000000000005172DOI Listing
July 2019

Bone and cortical bone characteristics of mandibular retromolar trigone and anterior ramus region for miniscrew insertion in adults.

Am J Orthod Dentofacial Orthop 2019 Mar;155(3):330-338

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Section of Orthodontics, School of Dentistry, University of Messina, Messina, Italy.

Introduction: The aim of this study was to evaluate bone depth, cortical bone thickness, and vestibulolingual bone dimension of the mandibular retromolar trigone and anterior ramus region to evaluate what are its most suitable sites for miniscrew insertion in adults.

Methods: The sample included cone-beam computerized tomography (CBCT) records of 60 adult subjects retrospectively evaluated. All CBCT examinations were performed with the use of an i-CAT CBCT scanner (Imaging Sciences International). Each exam was converted into DICOM format and processed with the use of Osirix Medical Imaging software. On reproducible sagittal scan views, bone depth and cortical bone thickness were evaluated on specific lines parallel and at a 45° angle to the occlusal plane, and at 3 mm and at 6 mm distance from it. Vestibulolingual bone dimension was computed in 4 different cross-section scans and at 3 different levels of depth (0, 6, and 11 mm).

Results: All of the considered insertion sites showed on average more than 10 mm of bone depth. Inferential statistics showed significantly (P <0.05) greater bone depth (+3 mm) in cross-sectional scans parallel to the occlusal plane compared with those at a 45° angle to it. Cortical bone thickness showed average values from 3 mm to 5 mm. Vestibulolingual bone dimension showed a significant (P <0.05) reduction (-10 mm) in the posterior region of retromolar region. No significant differences were found between subjects with and without third molars.

Conclusions: The retromolar trigone and anterior ramus region showed enough bone quantity and adequate bone quality for safe miniscrew insertion in adults.
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http://dx.doi.org/10.1016/j.ajodo.2018.04.025DOI Listing
March 2019

Treatment With a Flavonoid-Rich Fraction of Bergamot Juice Improved Lipopolysaccharide-Induced Periodontitis in Rats.

Front Pharmacol 2018 17;9:1563. Epub 2019 Jan 17.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.

In this study, we investigated the effects of a flavonoid-rich fraction of Bergamot juice (BJe) in rats subjected to experimental periodontitis induced by a single intragingival injection of lipopolysaccharides (LPS). Periodontitis was induced by a single intragingival injection of 1 μl LPS (10 μg/μl) derived from in sterile saline solution. The injection was made in the mesolateral side at the interdental papilla between the first and the second molar. Fourteen days after LPS injection, we performed radiographic analyses and then we surgically removed the gingivomucosal tissue surrounding the mandibular first molar for histological, immunohistochemical and molecular analysis. LPS significantly induced oedema, tissue damage and increased neutrophil infiltration. At molecular level, we found increased NF-κB translocation as well as raised both TNF-α and IL-1β expression, other than modulation of apoptosis-associated proteins. Moreover, the increased myeloperoxidase activity was associated with up-regulation of adhesion molecules. Immunohistochemical analysis for nitrotyrosine and poly ADP-ribose displayed an intense staining in the gingivomucosal tissue. Oral administration of BJe for 14 consecutive days reduced tissue injury and several markers of gingival inflammation including nuclear NF-κB translocation, cytokines expression, myeloperoxidase activity and the expression of some adhesion molecules such as ICAM and -selectin. BJe also decreased both nitrosative stress and PARP positive staining. Moreover, it caused down-regulation of Bax and up-regulation of Bcl-2 expression. Our findings demonstrate that BJe improves LPS-induced periodontitis in rats by reducing the typical markers of inflammation, thus suggesting its potential in the treatment of periodontal diseases.
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http://dx.doi.org/10.3389/fphar.2018.01563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345201PMC
January 2019

Appropriateness in Dentistry: A Survey Discovers Improper Procedures in Oral Medicine and Surgery.

Int J Dent 2018 4;2018:3245324. Epub 2018 Apr 4.

Department of Surgical, Oncological and Oral Sciences, University of Palermo, via Liborio Giuffrè 5, 90123 Palermo, Italy.

Objectives: The aim of this study was to assess appropriateness of diagnostic exams, treatments, and procedures among Italian dental practitioners.

Materials And Methods: A questionnaire with multiple responses on topics of dentistry and oral medicine was administered to a sample of 198 Italian dental practitioners. Information on characteristics of the respondents was also collected. Descriptive statistics and multiple correspondence analysis (MCA) were applied. Data were analyzed using R software (version 3.3.2).

Results: The survey respondents included Doctors of Medicine (MD) (54/198 = 27%) with or without specialty in dentistry (33% versus 67%), Doctors of Dental Surgery (DDS) (144/198 = 73%), DDS with specialty in orthodontics (7%), and DDS with specialty in oral surgery (4%). Mandatory procedures in dental and oral medicine education and training include (a) prescription of antibiotics before/after oral surgery procedures; (b) prevention strategies for oral cancer, and (c) prescription of dental X-ray examinations (41%, 52%, and 48%, resp.).

Conclusion: On examining the results of the survey, it is evident that information and implementation of the above mentioned procedures are crucially needed. Our results confirm the necessity to reduce inappropriate practices in dentistry, implementing formation and information, leading to correct prescriptions, and optimizing patients' oral health. This coincides with the Italian Slow Medicine program entitled "," which has also motivated this study.
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http://dx.doi.org/10.1155/2018/3245324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079469PMC
April 2018

Micronized palmitoylethanolamide reduces joint pain and glial cell activation.

Inflamm Res 2018 Oct 18;67(10):891-901. Epub 2018 Aug 18.

Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Viale Ferdinando Stagno d'Alcontres 31, 98166, Messina, Italy.

Objective And Design: Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation.

Materials And Subject: TMJ was induced in rats with the injection of complete Freund's adjuvant (CFA) emulsion into the left TMJ capsule.

Treatment: The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity.

Methods: Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection.

Results: CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1.

Conclusions: The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.
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http://dx.doi.org/10.1007/s00011-018-1179-yDOI Listing
October 2018

Could the Combined Administration of Bone Antiresorptive Drug, Taxanes, and Corticosteroids Worsen Medication Related Osteonecrosis of the Jaws in Cancer Patients?

Biomed Res Int 2018 29;2018:4021952. Epub 2018 May 29.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.

The study presents a report of 58 metastatic cancer patients who developed osteonecrosis of the jaws after being treated with zoledronic acid and taxanes, plus corticosteroids. A retrospective analysis of data registered in the archives of two Italian osteonecrosis of the jaws treatment centers, who are based at the University of Messina and at the University of Palermo, was performed in order to study, in these patients, demographic data and characteristics such as frequency of cancer location, lines of therapy, frequency of cancer drugs, presence/absence of oral trigger, number, location, and stage of jaw osteonecrosis. It was found that the majority of patients developed advanced stages of osteonecrosis, frequently complicated with infection. It was hypothesized that the concurrent administration of chemotherapeutic agents could be eventually considered as a factor able to allow a faster worsening of the clinical manifestation through the exacerbation of soft tissue defects, due to chemotherapy drugs.
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http://dx.doi.org/10.1155/2018/4021952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996467PMC
January 2019

Impact of electro-neuro-feedback on postoperative outcome of impacted lower third molar surgery.

Eur J Dent 2018 Jan-Mar;12(1):77-88

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Policlinic "Gaetano Martino", Messina, Italy.

Objective: The purpose of this study was to evaluate the impact of a treatment with electro-neuro-feedback (ENF), a portable transcutaneous electrical nerve stimulation (TENS) device, on the clinical outcome and inflammatory biochemical parameters related to the impacted lower third molar surgery.

Materials And Methods: A randomized, split-mouth, and single-blind study was conducted on 32 patients requiring lower third molars extractions and referred to the Oral Surgery Unit of the School of Dentistry of the University of Messina. Every patient underwent surgical removal of both lower third molars. The first extraction included a placebo (electrodes placement with turned-off device) treatment following the surgery, while the second had the ENF used next to the avulsion and the following days. Clinical parameters were collected 4 days before, immediately after, 2, 4, and 7 days after the surgical procedure. Biochemical parameters were obtained 1 day before the surgical removal and 7 days after. Data were processed using Wilcoxon-Mann-Whitney test, with significance being set at < 0.05.

Results: Clinical outcome parameters showed a significant improvement after the ENF treatment, while considered inflammatory markers expressed different patterns.

Conclusions: ENF, a reliable portable TENS device, has demonstrated to be a useful tool in the managing of the postsurgical phases, reducing edema, pain, and consequent pain-killers consumption.
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http://dx.doi.org/10.4103/ejd.ejd_296_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883481PMC
April 2018

Altered microRNA expression profile in the peripheral lymphoid compartment of multiple myeloma patients with bisphosphonate-induced osteonecrosis of the jaw.

Ann Hematol 2018 Jul 15;97(7):1259-1269. Epub 2018 Mar 15.

Department of Biomedical, Dental Science and Morphological and Functional Images, Dental School, Messina, Italy.

Bisphosphonates are formidable inhibitors of osteoclast-mediated bone resorption employed for therapy of multiple myeloma (MM) subjects with osteolytic lesions. Osteonecrosis of the jaw (ONJ) is an uncommon drug-induced adverse event of these agents. MicroRNAs (miRNAs) are a group of small, noncoding RNAs nucleotides, which are essential post-transcriptional controllers of gene expression. They have a central role in the normal bone development. The goal of our study was to investigate 18 miRNAs, whose targets were previously validated and described in MM subjects without ONJ, in peripheral lymphocytes of MM subjects with bisphosphonate-induced ONJ. Utilizing reverse transcription quantitative polymerase chain reaction, we evaluated miRNAs in five healthy subjects and in five MM patients with ONJ. Our experimental data revealed that a diverse miRNA signature for ONJ subjects emerged with respect to control subjects. Using the filter for in silico analysis, among the 18 miRNAs, we recognized 14 dysregulated miRNAs. All these miRNAs were significantly over-expressed in patients vs controls (MIR-16-1, MIR-21, MIR-23A, MIR-28, MIR-101-1, MIR-124-1, MIR-129, MIR-139, MIR-145, MIR-149, MIR-202, MIR-221, MIR-424, MIR-520). Among them, six were strongly upregulated (fourfold upregulated and more). These miRNAs target numerous pathways and genes implicated in calcium ion binding, bone resorption, mineralization of bone matrix, and differentiation and maintenance of bone tissue. A modified microRNA expression profile after zoledronate therapy could participate to the onset of ONJ. Targeting these miRNAs could provide a new opportunity for the prevention or treatment of ONJ.
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http://dx.doi.org/10.1007/s00277-018-3296-7DOI Listing
July 2018

Anti-inflammatory effect of ATB-352, a H2S -releasing ketoprofen derivative, on lipopolysaccharide-induced periodontitis in rats.

Pharmacol Res 2018 06 26;132:220-231. Epub 2017 Dec 26.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, no 31, Messina, 98166, Italy; Department of Pharmacological and Physiological Science, Saint Louis University, USA. Electronic address:

Periodontal disease is the most common cause of tooth loss in humans, is an inflammatory disease initiated by oral microbial biofilm. Given the involvement of the inflammatory pathway in this type of pathology, the main pharmacological strategy for the treatment of periodontitis, is the inhibition of the inflammatory process in order to prevent tissue destruction and bone resorption, a condition associated with a painful state. To do this, the best class of drugs are Non-steroidal anti-inflammatory drugs (NSAIDs), however, the presence of side effects, especially at the gastrointestinal tract, limits their use for long-term therapy. Recently, some evidence shows that derivatives of NSAIDs capable of releasing hydrogen sulphide exhibit lower collateral effects, particularly at the gastric level. In fact, H2S is an endogenous gaseous mediator with a cytoprotective role at the gastric level. In this study, we have compared the protective effects of ketoprofen with ATB-352, a hydrogen sulfide-releasing derivative of ketoprofen, in an experimental model of periodontitis in rat. Periodontitis was induced by a single intragingival injection of 1 μl LPS (10 μg/μl), Our results show that 14 h after intragingival injection of LPS, there was a high tissue damage associated with bone resorption, and in gingivomucosal tissues there was a significant expression of NF-kb p65 and pro-inflammatory cytokine as well as a higher expression of COX-2 and iNOS, activation of the apoptotic process, and also increased levels of NGF expression, often associated with a higher nociceptive perception. Treatment with ATB-352 at the dose of 20mg\kg, was able to reduce the inflammatory process associated with intragingival LPS injection and also had a positive effect on bone resorption and tissue damage.
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http://dx.doi.org/10.1016/j.phrs.2017.12.022DOI Listing
June 2018

Oral-Health-Related Quality of Life After Surgical Treatment of Osteonecrosis of the Jaws.

J Craniofac Surg 2018 Mar;29(2):403-408

Department of Biomedical, Dental Science and Morphological and Functional Images, Dental School, Messina, Italy.

The aim of this study is to analyze the clinical outcome and the change in oral-health-related quality of life (QoL) of osteoporotic patients affected by medication-related osteonecrosis of the jaws (MRONJ). Forty-one patients, consecutively treated for a 10-year period, were retrospectively analyzed. All the patients underwent a marginal osseous resective jaw surgery. A clinical 12 months postoperative evaluation has been performed and the complete mucosal healing, the absence of swelling and suppuration, and no signs of disease recurrence were defined like success parameters. Quality-of-life surveys tests like EORTC QQ-C30 and QLQ-HN35 appendices in conjunction with a perceived oral health visual analog scale (VAS) were administered before (time of diagnosis of MRONJ) and after surgery (at least 6 months) in order to record the different oral health status of the treated patients. The majority of MRONJ-diagnosed patients complained symptoms like pain, eating discomfort, and sense problems, with occasional involvement of the social dimension. There was a prevalence of troubles with social eating and social contact.The complete mucosal healing was achieved in 100% of the patients and the administered survey tests reported a significant improvement in all the investigated spheres. Similarly, an increased mean score of perceived oral health VAS was reported.Marginal-resective surgery of the necrotic jaw bone can be an effective treatment of osteoporotic patients affected by localized MRONJ. Quality-of-life parameters are demonstrated to be useful for recording the patient-centered outcome of MRONJ treatment.
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http://dx.doi.org/10.1097/SCS.0000000000004087DOI Listing
March 2018

Adenosine Receptor Stimulation Improves Glucocorticoid-Induced Osteoporosis in a Rat Model.

Front Pharmacol 2017 5;8:558. Epub 2017 Sep 5.

Department of Clinical and Experimental Medicine, University of MessinaMessina, Italy.

Glucocorticoid-induced osteoporosis (GIO) is a secondary cause of bone loss. Bisphosphonates approved for GIO, might induce jaw osteonecrosis; thus additional therapeutics are required. Adenosine receptor agonists are positive regulators of bone remodeling, thus the efficacy of adenosine receptor stimulation for treating GIO was tested. In a preventive study GIO was induced in Sprague-Dawley rats by methylprednisolone (MP) for 60 days. Animals were randomly assigned to receive polydeoxyribonucleotide (PDRN), an adenosine A2 receptor agonist, or PDRN and DMPX (3,7-dimethyl-1-propargylxanthine, an A antagonist), or vehicle (0.9% NaCl). Another set of animals was used for a treatment study, following the 60 days of MP-induction rats were randomized to receive (for additional 60 days) PDRN, or PDRN and DMPX (an adenosine A2 receptor antagonist), or zoledronate (as control for gold standard treatment), or vehicle. Control animals were administered with vehicle for either 60 or 120 days. Femurs were analyzed after treatments for histology, imaging, and breaking strength analysis. MP treatment induced severe bone loss, the concomitant use of PDRN prevented the developing of osteoporosis. In rats treated for 120 days, PDRN restored bone architecture and bone strength; increased b-ALP, osteocalcin, osteoprotegerin and stimulated the Wnt canonical and non-canonical pathway. Zoledronate reduced bone resorption and ameliorated the histological features, without significant effects on bone formation. Our results suggest that adenosine receptor stimulation might be useful for preventing and treating GIO.
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http://dx.doi.org/10.3389/fphar.2017.00558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591884PMC
September 2017

Spontaneous Healing of Clodronate-Related Osteonecrosis of the Jaw.

J Craniofac Surg 2017 Oct;28(7):e687-e689

Department of Biomedical, Dental Science and Morphological and Functional Images, Dental School, University of Messina, Messina, Italy.

Cases of medication-related osteonecrosis of the jaw (MRONJ) have been more commonly associated with aminobiphosphonate therapy than with alkylbiphosphonate treatment. Here, we report a case of MRONJ in a subject who received an alkylbiphosphonate, clodronate, for the treatment of osteoporosis, and discuss the pathogenic mechanisms of alkylbiphosphonates and the possible reasons for the spontaneous and rapid remission of MRONJ occurring in our patient.
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http://dx.doi.org/10.1097/SCS.0000000000003837DOI Listing
October 2017

Treatment of Medication-Related Osteonecrosis of the Jaw and its Impact on a Patient's Quality of Life: A Single-Center, 10-Year Experience from Southern Italy.

Drug Saf 2018 01;41(1):111-123

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, 98125, Messina, Italy.

Introduction: No official guidelines are available for the management of medication-related osteonecrosis of the jaw (MR-ONJ). The additional benefit of surgery after pharmacological treatment is debated by both clinicians and patients.

Objective: The aim of this study was to evaluate the changes in patients' MR-ONJ-related quality of life (QoL) after pharmacological treatment with or without surgery in a large cohort affected by MR-ONJ.

Methods: Anonymized data on patients diagnosed with MR-ONJ were extracted from the database of the Osteonecrosis of the Jaw Treatment Center (University of Messina, Italy) in the years 2005-2015. QoL was evaluated at the moment of MR-ONJ diagnoses (T0), after pharmacological treatment with or without surgery (T1 and T2, respectively), based on scores from the European Organisation for Research and Treatment of Cancer (EORTC) QOL Module for Head and Neck Cancer (global oral health status [GOHS]) and a visual analog scale (VAS), stratified by indication for use.

Results: Among 100 patients, 36% were affected by osteoporosis (OSTEO group) and 64% were affected by cancer (ONC group). Considering T0, QoL scores were higher in the OSTEO group then in the ONC group. At T1, GOHS and VAS increased in both groups (OSTEO group: +9.9% and +39.9%; ONC group: +35.4 and +97.2%, respectively). Pharmacological treatment was effective in reducing pain (OSTEO group: -22.0%; ONC group: -44.8%), and social contact troubles (OSTEO group: -40.3%; ONC group: -26.7%). At T2, GOHS and VAS further increased. Scores related to 'pain' and the troubles related to the 'social dimension' also decreased (OSTEO group: -91.3% and -72.0%; ONC group: 50.8% and -16.4%, respectively).

Conclusions: MR-ONJ-related QoL increased after pharmacological treatment and, more notably, after surgery, which may offer benefits to selected patients. QoL data may help clinicians in promoting tailored management of MR-ONJ.
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http://dx.doi.org/10.1007/s40264-017-0582-6DOI Listing
January 2018

Does Vitamin D3 Have an Impact on Clinical and Biochemical Parameters Related to Third Molar Surgery.

J Craniofac Surg 2016 Mar;27(2):469-76

*Department of Experimental Medical-Surgical Sciences and Dentistry †Department of Odontostomatology, School of Dentistry ‡Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

The purpose of this study was to evaluate the clinical effect on the biochemical inflammatory markers of a single oral high dose of cholecalciferol in vitamin D-deficient patients undergoing the surgical removal of lower third molars.A randomized, split-mouth, single-blind study was conducted on 25 vitamin D-deficient patients ranging between 18 and 40 years of age requiring lower third molars extraction and referred at the Oral Surgery Unit of the School of Dentistry of the University of Messina.All patients, with vitamin D3 blood levels ≦30 ng/mL, underwent bilateral surgical removal. The first extraction (control group) being conducted with the administration of a placebo, the second one (test group) being conducted with the preliminary administration of 300,000 IU of cholecalciferol 4 days before the procedure.At each surgery, clinical indexes, such as pain, edema and any functional limitation have been recorded. Clinical and biochemical parameters were registered 4 days before, immediately after, 3 and 7 days after the surgical procedure. The data obtained were processed using paired t-test. The clinical outcome parameters showed a slight to moderate improvement between the control and the vitamin-D treatment group, with statistical significance being obtained regarding the edema at defined time points. Interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha values were significantly lower (P < 0.01) for the test group after the surgery. The increase of vitamin D serum levels showed an impact on the outcome of the third molar surgery, eliciting a reduced inflammatory response and leading to a more favorable clinical course.
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http://dx.doi.org/10.1097/SCS.0000000000002389DOI Listing
March 2016

Peripheral desmoplastic ameloblastoma in adolescent age: clinico-pathological and immunohistochemical analisys of a case.

Open Dent J 2014 29;8:159-63. Epub 2014 Sep 29.

Department of Human Pathology, University of Messina, Italy.

The Extraosseous or Peripheral Ameloblastoma (PA) is a rare and benign odontogenic tumour, representing 1% to 5% of all ameloblastomas. It is usually localized in the soft oral tissues, without deep bone involvement. Its biological behaviour is specific, and several authors define PA as a non-infiltrating hamartomatous lesion. Indeed, recurrences rarely occur and progression in malignant tumors appears to be rare. The PA originates from the tooth-forming apparatus and it consists of proliferating odontogenic epithelium, exhibiting the same histological cell types and patterns of the intraosseous counterpart or infiltrating ameloblastoma. The peripheral desmoplastic ameloblastoma (PDA) can be classified as a newly recognized and very rare histological variant. To our knowledge, only a few cases of adult patients affected by PDA have been published. The aim of this paper is to report a case of PDA affecting an adolescent patient. The clinical-pathological and immunohistological features are discussed in order to improve knowledge regarding a correct diagnosis and to differentiate PDA lesions from similar diseases.
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http://dx.doi.org/10.2174/1874210601408010159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192832PMC
October 2014

Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed.

Br J Oral Maxillofac Surg 2015 Jan 2;53(1):13-7. Epub 2014 Oct 2.

University and Hospital Trust of Verona, Department of Surgery, Section of Oral and Maxillofacial Surgery, Verona, Italy.

Recent data suggest that the traditional definition of bisphosphonate-associated osteonecrosis of the jaw (ONJ) may exclude patients who present with the non-exposed variant of the condition. To test the hypothesis that a proportion of patients with ONJ remain undiagnosed because their symptoms do not conform to the traditional case definition, we did a secondary analysis of data from MISSION (Multicentre study on phenotype, definition and classification of osteonecrosis of the jaws associated with bisphosphonates), a cross-sectional study of a large population of patients with bisphosphonate-associated ONJ who were recruited in 13 European centres. Patients with exposed and non-exposed ONJ were included. The main aim was to quantify the proportion of those who, according to the traditional case definition, would not be diagnosed with ONJ because they had no exposed necrotic bone. Data analysis included descriptive statistics, median regression, and Fisher's exact test. A total of 886 consecutive patients were recruited and 799 were studied after data cleaning (removal or correction of inaccurate data). Of these, 607 (76%) were diagnosed according to the traditional definition. Diagnosis in the remaining 192 (24%) could not be adjudicated, as they had several abnormal features relating to the jaws but no visible necrotic bone. The groups were similar for most of the phenotypic variables tested. To our knowledge this is the first study in a large population that shows that use of the traditional definition may result in one quarter of patients remaining undiagnosed. Those not considered to have ONJ had the non-exposed variant. These findings show the importance of adding this description to the traditional case definition.
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http://dx.doi.org/10.1016/j.bjoms.2014.09.001DOI Listing
January 2015

Polyethylene glycol formulations show different soft tissue remodeling and angiogenesis features.

Tissue Eng Part A 2015 Feb 12;21(3-4):580-5. Epub 2014 Nov 12.

1 Department of Dentistry and Medical and Surgical Experimental Sciences, University of Messina , Messina, Italy .

Background: Soft tissue regeneration and remodeling is fundamental in periodontal surgery, thus we investigated the angiogenic response elicited in the subcutaneous tissue of rats by a proprietary, polyethylene glycol hydrogel formulation (PEG) alone or conjugated with specific amelogenins (EMD) or nanobioglass particles (NBG).

Methods: Discs with three different formulations (PEG, PEG-EMD, and PEG-NBG) were inserted into four unconnected subcutaneous pouches, produced on the back of Sprague-Dawley rats (n=56, divided into three groups), and used for blood flow evaluation by Laser Doppler analysis at 1, 2, 4, 8, and 16 weeks or for histological and immunohistochemical analysis at 1, 2, 4, 8, and 16 weeks.

Results: All formulations showed tissue integration, absence of inflammatory reaction (as revealed by myeloperoxidase staining), and increased vascularization (by counting microvascular density following CD31 staining). Laser Doppler analysis revealed a statistically significant increase in blood flow after 1 week for PEG-EMD and after 2 weeks for PEG-NBG. The angiogenic response was significantly increased at 1, 2, and 8 weeks for PEG-EMD, but only at 4 weeks for PEG-NBG.

Conclusions: The studied biomaterials revealed equal biocompatibility and tissue integration properties. PEG-EMD showed the most pronounced and consistent angiogenic response in the early phases of wound healing, while the PEG-NBG formulation provided a slower and delayed, but relevant, response.
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http://dx.doi.org/10.1089/ten.TEA.2014.0260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333316PMC
February 2015