Computer-aided designed 3D-printed polymeric scaffolds for personalized reconstruction of maxillary and mandibular defects: a proof-of-concept study.

PURPOSE: To investigate the potential reconstruction of complex maxillofacial defects using computer-aided design 3D-printed polymeric scaffolds by defining the production process, simulating the surgical procedure, and explore the feasibility and reproducibility of the whole algorithm. METHODS: This a preclinical study to investigate feasibility, reproducibility and efficacy of the reconstruction algorithm proposed. It encompassed 3 phases: (1) scaffold production (CAD and 3D-printing in polylactic acid); (2) surgical simulation on cadaver heads (navigation-guided osteotomies and scaffold fixation); (3) assessment of reconstruction (bone and occlusal morphological conformance, symmetry, and mechanical stress tests). RESULTS: Six cadaver heads were dissected. Six types of defects (3 mandibular and 3 maxillary) with different degree of complexity were tested. In all case the reconstruction algorithm could be successfully completed. Bone morphological conformance was optimal while the occlusal one was slightly higher. Mechanical stress tests were good (mean value, 318.6 and 286.4 N for maxillary and mandibular defects, respectively). CONCLUSIONS: Our reconstructive algorithm was feasible and reproducible in a preclinical setting. Functional and aesthetic outcomes were satisfactory independently of the complexity of the defect.

Assessment of Atlanto-Axial and Mandibular Rotation by Cone Beam Computed Tomography.

The cranial portion of the vertebral segment together with the atlanto-occipital joint represents a very complex area. Since this system could be influenced by different atlas and mandibular position, the aim of this work was to assess atlanto-axial and mandibular rotation. Scanora 3-dimensional cone bean computed tomography images from 205 patients without signs or symptoms of temporomandibular disorder were evaluated. Using a digitalized images analyzer, the axial rotations of atlas and mandible rotation were calculated, measuring the angle with respect to the frontal plane. The same direction for the axial rotation of the mandible and for the atlanto-axial rotation (consistent group) was observed in 80.98% of the patients; opposite directions (inconsistent group) were observed in 19.02%. Among the consistent group, the left rotation was observed in 71.08% of the patients and the right rotation in 28.92%. Absolute values showed a more marked rotation for atlas than mandible and higher values for the left rotation were reported for both.Taking together these data represents important starting points for the knowledge of atlas and mandible relationship and its functional and clinical implication.

Quantitative Anatomical Comparison of Surgical Approaches to Meckel's Cave.

BACKGROUND: Meckel's cave is a challenging surgical target due to its deep location and proximity to vital neurovascular structures. Surgeons have developed various microsurgical transcranial approaches (MTAs) to access it, but there is no consensus on the best method. Newer endoscopic approaches have also emerged. This study seeks to quantitatively compare these surgical approaches to Meckel's cave, offering insights into surgical volumes and exposure areas. METHODS: Fifteen surgical approaches were performed bilaterally in six specimens, including the pterional approach (PTA), fronto-temporal-orbito-zygomatic approach (FTOZA), subtemporal approach (STA), Kawase approach (KWA), retrosigmoid approach (RSA), retrosigmoid approach with suprameatal extension (RSAS), endoscopic endonasal transpterygoid approach (EETPA), inferolateral transorbital approach (ILTEA) and superior eyelid approach (SEYA). All the MTAs were performed both with 10 mm and 15 mm of brain retraction, to consider different percentages of surface exposure. A dedicated navigation system was used to quantify the surgical working volumes and exposure of different areas of Meckel's cave (ApproachViewer, part of GTx-Eyes II, University Health Network, Toronto, Canada). Microsurgical transcranial approaches were quantified with two different degrees of brain retraction (10 mm and 15 mm). Statistical analysis was performed using a mixed linear model with bootstrap resampling. RESULTS: The RSAS with 15 mm of retraction offered the maximum exposure of the trigeminal stem (TS). If compared to the KWA, the RSA exposed more of the TS (69% vs. 46%; p = 0.01). The EETPA and ILTEA exposed the Gasserian ganglion (GG) mainly in the anteromedial portion, but with a significant 20% gain in exposure provided by the EETPA compared to ILTEA (42% vs. 22%; p = 0.06). The STA with 15 mm of retraction offered the maximum exposure of the GG, with a significant gain in exposure compared to the STA with 10 mm of retraction (50% vs. 35%; p = 0.03). The medial part of the three trigeminal branches was mainly exposed by the EETPA, particularly for the ophthalmic (66%) and maxillary (83%) nerves. The EETPA offered the maximum exposure of the medial part of the mandibular nerve, with a significant gain in exposure compared to the ILTEA (42% vs. 11%; p = 0.01) and the SEY (42% vs. 2%; p = 0.01). The FTOZA offered the maximum exposure of the lateral part of the ophthalmic nerve, with a significant gain of 67% (p = 0.03) and 48% (p = 0.04) in exposure compared to the PTA and STA, respectively. The STA with 15 mm of retraction offered the maximum exposure of the lateral part of the maxillary nerve, with a significant gain in exposure compared to the STA with 10 mm of retraction (58% vs. 45%; p = 0.04). The STA with 15 mm of retraction provided a significant exposure gain of 23% for the lateral part of the mandibular nerve compared to FTOZA with 15 mm of retraction (p = 0.03). CONCLUSIONS: The endoscopic approaches, through the endonasal and transorbital routes, can provide adequate exposure of Meckel's cave, especially for its more medial portions, bypassing the impediment of major neurovascular structures and significant brain retraction. As far as the most lateral portion of Meckel's cave, MTA approaches still seem to be the gold standard in obtaining optimal exposure and adequate surgical volumes.

Association between Peri-Implant Soft Tissue Health and Different Prosthetic Emergence Angles in Esthetic Areas: Digital Evaluation after 3 Years' Function.

BACKGROUND: The aim of the present retrospective study was to assess peri-implant soft tissue health for implants restored with different prosthetic emergence profile angles. METHODS: Patients were treated with implants supporting fixed dentures and were followed for 3 years. Buccal emergence angle (EA) measured at 3 years of follow-up visits (t1) were calculated for two different groups: Group 1 (153 implants) for restorations with angle between implant axis and prosthetic emergence angle from ≥30°, and Group 2 (67 implants) for those with angle ≤30°, respectively. Image J software was used for the measurements. Moreover, peri-implant soft tissue parameters such as pocket probing depth (PPD), plaque index (PI) and gingival index (GI) were assessed, respectively. RESULTS: A total of 57 patients were included in the analysis and a total of 220 implants were examined. Mean (±SD) EA in Groups 1 and 2 was 46.4 ± 12.2 and 24.5 ± 4.7 degrees, respectively. After 3 years of follow-up, a PPD difference of 0.062 mm (CI95% -0.041 mm; 0.164 mm) was calculated between the two groups and was not statistically significant (p = 0.238). Similar results were found for PI (OR = 0.78, CI95% 0.31; 1.98, p = 0.599). Furthermore, GI scores of 2 and 3 were found for nine implants (5.9%) in Group 1, and for five implants in Group 2 (7.5%). A non-significant difference (p = 0.76) was found. CONCLUSIONS: Peri-implant soft-tissue health does not seem to be influenced by EA itself, when a proper emergence profile is provided for implant-supported reconstructions in anterior areas.

Peripheral Purinergic Modulation in Pediatric Orofacial Inflammatory Pain Affects Brainstem Nitroxidergic System: A Translational Research.

Physiology of orofacial pain pathways embraces primary afferent neurons, pathologic changes in the trigeminal ganglion, brainstem nociceptive neurons, and higher brain function regulating orofacial nociception. The goal of this study was to investigate the nitroxidergic system alteration at brainstem level (spinal trigeminal nucleus), and the role of peripheral P2 purinergic receptors in an experimental mouse model of pediatric inflammatory orofacial pain, to increase knowledge and supply information concerning orofacial pain in children and adolescents, like pediatric dentists and pathologists, as well as oro-maxillo-facial surgeons, may be asked to participate in the treatment of these patients. The experimental animals were treated subcutaneously in the perioral region with pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a P2 receptor antagonist, 30 minutes before formalin injection. The pain-related behavior and the nitroxidergic system alterations in the spinal trigeminal nucleus using immunohistochemistry and western blotting analysis have been evaluated. The local administration of PPADS decreased the face-rubbing activity and the expression of both neuronal and inducible nitric oxide (NO) synthase isoforms in the spinal trigeminal nucleus. These results underline a relationship between orofacial inflammatory pain and nitroxidergic system in the spinal trigeminal nucleus and suggest a role of peripheral P2 receptors in trigeminal pain transmission influencing NO production at central level. In this way, orofacial pain physiology should be elucidated and applied to clinical practice in the future.

Step-by-Step Cadaver Dissection and Surgical Technique for Compartmental Tongue and Floor of Mouth Resection.

BACKGROUND: The aim of oral cancer surgery is tumor removal within clear margins of healthy tissue: the latter definition in the literature, however, may vary between 1 and 2 cm, and should be intended in the three dimensions, which further complicates its precise measurement. Moreover, the biological behavior of tongue and floor of mouth cancer can be unpredictable and often eludes the previously mentioned safe surgical margins concept due to the complexity of tongue anatomy, the intricated arrangements of its intrinsic and extrinsic muscle fibers, and the presence of rich neurovascular and lymphatic networks within it. These structures may act as specific pathways of loco-regional tumor spread, allowing the neoplasm to escape beyond its visible macroscopic boundaries. Based on this concept, in the past two decades, compartmental surgery (CS) for treatment of oral tongue and floor of mouth cancer was proposed as an alternative to more traditional transoral resections. METHODS: The authors performed three anatomical dissections on fresh-frozen cadaver heads that were injected with red and blue-stained silicon. All procedures were documented by photographs taken with a professional reflex digital camera. RESULTS: One of these step-by-step cadaver dissections is herein reported, detailing the pivotal points of CS with the aim to share this procedure at benefit of the youngest surgeons. CONCLUSIONS: We herein present the CS step-by-step technique to highlight its potential in improving loco-regional control by checking all possible routes of tumor spread. Correct identification of the anatomical space between tumor and nodes (T-N tract), spatial relationships of extrinsic tongue muscles, as well as neurovascular bundles of the floor of mouth, are depicted to improve knowledge of this complex anatomical area.

A comparative pilot study of two dental implant metals in a pig model.

PURPOSE: Successful implant treatment is based on implant stability, absence periimplant inflammation, and a functional interface between implant and bone tissue (direct bone-implant contact). The aim of this preliminary study on a pig model was to investigate how implant osseointegration was influenced by a new implant alloy. MATERIALS: Cobalt-chrome experimental implants were compared clinically and histologically with titanium implants, after a loaded healing period of 6 months. RESULTS: The clinical analyses showed absence of mobility, abscesses, or inflammation, whereas the histological analysis showed the apposition of new bone tissue that established a direct contact with implants. The comparison of different implant alloys revealed no statistical differences between the osseointegration process of tested implants and control titanium implants. CONCLUSION: This study revealed no significant short-term difference between the use of titanium and a chrome-cobalt alloy in implant effectiveness in the process of osseointegration.

Periodontitis Stage III-IV, Grade C and Correlated Factors: A Histomorphometric Study.

BACKGROUND: Periodontitis is a disease that leads to serious functional and esthetic dysfunctions. Periodontitis exists in different forms, and its etiology is related to multiple component causes. Two key processes involved in the evolution of this pathology are angiogenesis and inflammatory infiltrate. The aim of this study was to understand if important factors such as smoking, gender, age, plaque, pus, and probing pocket depth could influence the histomorphological pattern of generalized stage III-IV, grade C periodontitis (GPIII-IVC), which is a particular form of periodontitis. METHODS: Eighteen subjects with GPIII-IVC were enrolled in this study. The percentage of inflammatory cells and the vascular area were measured and evaluated in relation to each periodontal disease-associated factor. RESULTS: Females showed a significant increase in the percentage of inflammatory cells compared to males (6.29% vs. 2.28%, p-value = 0.020) and it was higher in non-smokers than in smokers (4.56% vs. 3.14%, p-value = 0.048). Young patients showed a significant increase in vascular area percentage compared to older patients (0.60% vs. 0.46%, p-value = 0.0006) and this percentage was also higher in non-smokers compared to smokers (0.41% vs. 0.55%, p-value = 0.0008). The vascular area was also more than halved in subjects with residual plaque on tooth surfaces (0.74% vs. 0.36%, p-value = 0.0005). CONCLUSIONS: These results suggested that even if these factors are commonly related to the worsening of periodontal status, some of them (pus and periodontal probing depth (PPD)) do not affect the inflammatory and vascular patterns.

Beneficial Effects of Concentrated Growth Factors and Resveratrol on Human Osteoblasts In Vitro Treated with Bisphosphonates.

Bisphosphonates are primary pharmacological agents against osteoclast-mediated bone loss and widely used in the clinical practice for prevention and treatment of a variety of skeletal conditions, such as low bone density and osteogenesis imperfecta, and pathologies, such as osteoporosis, malignancies metastatic to bone, Paget disease of bone, multiple myeloma, and hypercalcemia of malignancy. However, long-term bisphosphonate treatment is associated with pathologic conditions including osteonecrosis of the jaw, named BRONJ, which impaired bone regeneration process. Clinical management of BRONJ is controversy and one recent approach is the use of platelet concentrates, such as Concentrated Growth Factors, alone or together with biomaterials or antioxidants molecules, such as resveratrol. The aim of the present study was to investigate the in vitro effects of Concentrated Growth Factors and/or resveratrol on the proliferation and differentiation of human osteoblasts, treated or not with bisphosphonates. Human osteoblasts were stimulated for 3 days in complete medium and for 21 days in mineralization medium. At the end of the experimental period, the in vitro effect on osteoblast proliferation and differentiation was evaluated using different techniques such as MTT, ELISA for the quantification/detection of osteoprotegerin and bone morphogenetic protein-2, immunohistochemistry for sirtuin 1 and collagen type I, and the Alizarin Red S staining for the rate of mineralization. Results obtained showed that Concentrated Growth Factors and/or resveratrol significantly increased osteoblast proliferation and differentiation and that the cotreatment with Concentrated Growth Factors and resveratrol had a protective role on osteoblasts treated with bisphosphonates. In conclusion, these data suggest that this approach could be promised in the clinical management of BRONJ.

Anterior superior alveolar nerve injury after extended endoscopic medial maxillectomy: a preclinical study to predict neurological morbidity.

BACKGROUND: Endoscopic medial maxillectomies (EMMs) are used to optimize exposure of the maxillary sinus and retromaxillary areas. Although in type D EMM (Sturmann-Canfield procedure) the anterior superior alveolar nerve (ASAN) is always at risk of injury, only 29% of patients complained of alveolar process and dental anesthesia. The purpose of this anatomical study is to assess the neural anastomotic network of the ASAN (ASAN-NAN) and describe different extensions of type D EMMs in a preclinical setting. METHODS: The ASAN and its medial anastomotic branches (MABs) and lateral anastomotic branches (LABs) were evaluated by cone-beam computerized tomography (CBCT). Five different extensions of type D (D1 to D5) EMMs were identified and nerves at risk of injury in each type were assessed by CBCT. Moreover, quantification of surgical corridors was performed on cadaver heads with a neuronavigation system. RESULTS: Fifty-seven CBCT scans were analyzed. The ASAN would be spared in 16.3% of cases with a type D1 EMM, while it would be injured in the majority of type D2 to D5 resections. At least 1 nerve of the ASAN-NAN was spared in 96.6%, 93%, 74.6%, 0%, and 65.8% of type D1 to D5 EMMs, respectively. Two cadaver heads were dissected and the incremental volume and number of maxillary subsites exposed was assessed in type D1 to D5 EMMs. CONCLUSION: ASAN function impairment is probably compensated by LABs and MABs. If this hypothesis will be validated in a prospective study on patients, preoperative CBCT evaluation could predict neurological morbidity after type D EMM, and allow tailoring the procedure to minimize impairment of the ASAN-NAN.

Sodium-DNA for Bone Tissue Regeneration: An Experimental Study in Rat Calvaria.

Surgical techniques in dental and maxillofacial surgery request fast bone tissue regeneration, so there is a significant need to improve therapy for bone regeneration. Several studies have recently underlined the importance of nucleotides and nucleosides to increase cell proliferation and activity; in particular, the ability of polydeoxyribonucleotide (PDRN) to induce growth and activity of human osteoblasts was demonstrated. Sodium-DNA is the deoxyribonucleic acid (DNA) extracted from the gonadic tissue of male sturgeon and then purified, depolymerized, and neutralized with sodium hydroxide. To date, there are no evidences about the use of Sodium-DNA for bone tissue regeneration. Consequently, our question is about the efficacy of Sodium-DNA in bone healing. For testing the role of Sodium-DNA in bone healing we used a rat calvarial defect model. Sodium-DNA at different concentrations used alone or in association with Fibrin and/or Bio-Oss was used for healing treatments and the bone healing process was evaluated by histomorphometric and immunohistochemical analyses. Our results suggested a positive effect of Sodium-DNA in bone regeneration, providing a useful protocol and a model for the future clinical evaluation of its osteogenic properties.

Piezoelectric ultrasonic bone surgery system in the extraction surgery of supernumerary teeth.

INTRODUCTION: The anterior maxillary region is a common site for supernumerary teeth. The aim of this study was to compare the use of piezoelectric ultrasonic bone surgery for the extraction of supernumerary teeth and the use of traditional method using bone chisels. METHODS: 60 patients with supernumerary anterior maxillary teeth were considered in this study. They were randomly divided into two groups: 1) the control group, in which the supernumerary teeth were extracted using the traditional bone chisels method; 2) the experimental group, in which the supernumerary teeth were extracted using a piezoelectric ultrasonic bone surgery system. The operative time, amount of bleeding and post-operative pain were quantified and compared; in addition, the post-operative swelling was evaluated. RESULTS: We observed a significant decrease (P < 0.01) in the amount of bleeding and post-operative pain in the experimental group respect to the control group; but the operative time was significantly increased (P < 0.01) with the use of piezoelectric system. In addition, post-operative swelling resolved more quickly in the experimental group. CONCLUSION: Although the operative time for the extraction of the maxillary anterior supernumerary teeth was longer using the piezoelectric ultrasonic bone surgery system, the amount of bleeding and the post-operative complications were less, so this system could be considered an appropriate surgical method for the extraction of supernumerary teeth.

AQP1 expression in human gingiva and its correlation with periodontal and peri-implant tissue alterations.

Aquaporins (AQPs) are a family of hydrophobic integral membrane proteins that function as transmembrane channels and play an important role in tissue homeostasis. Aquaporin-1 (AQP1), in particular, has been reported to be involved in several biological processes including inflammation, angiogenesis, wound healing and others. Periodontitis and peri-implantitis can be defined as inflammatory processes that affect the tissues surrounding a tooth or an osseointegrated implant, respectively. To date, there are limited data about the involvement of AQPs in these diseases. The aim of this study was to evaluate the possible link between the histomorphological alterations and the expression of AQP1 in healthy, pathological and healed periodontal and peri-implant gingival tissues. The results obtained showed that changes in organization of collagen fibers were observed in periodontitis and peri-implantitis, together with an increase in the percentage of area occupied by inflammatory cell infiltration and an increase of AQP1 immunostaining, which was located in the endothelial cells of the vessels within the lamina propria. Moreover, in healed periodontal and peri-implant mucosa a restoration of histomorphological alterations was observed together with a concomitant decrease of AQP1 immunostaining. These data suggested a possible link between the degree of inflammatory state and the presence of AQP1, where the latter could be involved in the chain of inflammatory reactions triggered at periodontal and peri-implant levels.

Histomorphometrical evaluation of fresh frozen bone allografts for alveolar bone reconstruction: preliminary cases comparing femoral head with iliac crest grafts.

PURPOSE: In the past few years, the use of fresh frozen bone (FFB) grafts has significantly increased. The aim of this study was to evaluate the reconstruction of alveolar bone using femoral head and iliac crest FFB grafts. MATERIALS AND METHODS: The study included 10 patients who need endosseous implant insertion in severe atrophic maxillae. The patients were treated with FFB grafts collected from the femoral head or iliac crest. Bone regeneration was evaluated 6 months after surgery by macroscopic and microscopic analyses. RESULTS: Our results showed good regenerative capacity, both with the FFB from the femoral head and iliac crest. In particular, similar percentages of new-bone formation and graft residual were observed, whereas differences between the percentage of total bone (higher for the iliac crest) and the percentage of non-mineralized tissue (higher for the femoral head) were present. A significantly higher percentage of CD34-positive vessels in the FFB allograft from the femoral head than in the iliac crest were observed. CONCLUSIONS: These findings suggest that FFB allografts could represent a reliable option in oral and maxillofacial surgery. Nevertheless, differences between the use of femoral head or iliac crest bone allografts linked with their different structures should be considered for a more effective surgery.

Role of mast cells in wound healing process after glass-fiber composite implant in rats.

Glass-fiber composites are frequently used in dentistry. In order to evaluate their biocompatibility we tested, in an experimental model "in vivo", their tissue response pointing our attention on presence of mast cells (MCs) and fibrotic process. Sprague Dawley rats were used for the experimental design. The fibers were introduced in a subcutaneous pocket along the middle dorsal line between the two scapulas for 7, 14 or 21 days. At the end of the treatments the skins were excised and then processed for Toluidine Blue, to determine the presence of MCs, and Picrosirius Red staining, to evaluate the presence of fibrotic tissue. Our preliminary results showed and increase of both MC number and deposition of collagen type I, which characterized the fibrotic tissue. So, subsequent aims of our study were to evaluate the role played by MCs in tissue fibrosis and to give a possible explanation regarding the mechanisms that were responsible of biological response observed, through the analyses of some proteins, such as metalloproteinase-2 (MMP-2), its inhibitor (TIMP-2) and transforming growth factor-beta (TGF-beta). Our data confirmed the involvement of TGF-beta, released by MCs, in the disruption of the equilibrium between MMP-2 and TIMP-2 that were implicated in the enhancement of fibrosis. In summary, this study demonstrate that this type of materials induced an inflammatory response at the site of implant and help to clarify what type of mechanism and which proteins are involved in this biological response. Nevertheless, more extensive investigations are in progress to better evaluate the inflammatory process.