Regeneration of Critical-Sized Mandibular Defects Using 3D-Printed Composite Scaffolds: A Quantitative Evaluation of New Bone Formation in In Vivo Studies.

Mandibular tissue engineering aims to develop synthetic substitutes for the regeneration of critical size defects (CSD) caused by a variety of events, including tumor surgery and post-traumatic resections. Currently, the gold standard clinical treatment of mandibular resections (i.e., autologous fibular flap) has many drawbacks, driving research efforts toward scaffold design and fabrication by additive manufacturing (AM) techniques. Once implanted, the scaffold acts as a support for native tissue and facilitates processes that contribute to its regeneration, such as cells infiltration, matrix deposition and angiogenesis. However, to fulfil these functions, scaffolds must provide bioactivity by mimicking natural properties of the mandible in terms of structure, composition and mechanical behavior. This review aims to present the state of the art of scaffolds made with AM techniques that are specifically employed in mandibular tissue engineering applications. Biomaterials chemical composition and scaffold structural properties are deeply discussed, along with strategies to promote osteogenesis (i.e., delivery of biomolecules, incorporation of stem cells, and approaches to induce vascularization in the constructs). Finally, a comparison of in vivo studies is made by taking into consideration the amount of new bone formation (NB), the CSD dimensions, and the animal model.

Significant association between FGFR1 mutation frequency and age in central giant cell granuloma.

Central giant cell granulomas (CGCG) are rare intraosseous osteolytic lesions of uncertain aetiology. Despite the benign nature of this neoplasia, the lesions can rapidly grow and become large, painful, invasive, and destructive. The identification of molecular drivers could help in the selection of targeted therapies for specific cases. TRPV4, KRAS and FGFR1 mutations have been associated with these lesions but no correlation between the mutations and patient features was observed so far. In this study, we analysed 17 CGCG cases of an Italian cohort and identified an interesting and significant (p=0.0021) correlation between FGFR1 mutations and age. In detail, FGFR1 mutations were observed frequently and exclusively in CGCG from young (<18 years old) patients (4/5 lesions, 80%). Furthermore, the combination between ours and previously published data confirmed a significant difference in the frequency of FGFR1 mutations in CGCG from patients younger than 18 years at the time of diagnosis (9/23 lesions, 39%) when compared to older patients (1/31 lesions, 0.03%; p=0.0011), thus corroborating our observation in a cohort of 54 patients. FGFR1 variants in young CGCG patients could favour fast lesion growth, implying that they seek medical attention earlier. Our observation might help prioritise candidates for FGFR1 testing, thus opening treatment options with FGFR inhibitors.

Effects on Muscular Activity after Surgically Assisted Rapid Palatal Expansion: A Prospective Observational Study.

The study aims to investigate the modifications in the temporalis and the masseter activity in adult patients before and after SARPE (Surgically Assisted Rapid Palatal Expansion) by measuring electromyographic and electrokinesographic activity. 24 adult patients with unilateral posterior crossbite on the right side were selected from the Orthodontic Department of the University of Milan. Three electromyographic and electrokinesographic surface readings were taken respectively before surgery (T0) and 8 months after surgery (T1). The electromyographic data of both right and left masseter and anterior temporalis muscles were recorded during multiple tests: standardized maximum voluntary contraction (MVC)s, after transcutaneous electrical nerve stimulation (TENS) and at rest. T0 and T1 values were compared with paired Student's t-test (p < 0.05). Results: Significant differences were found in the activity of right masseter (p = 0.03) and right temporalis (p = 0.02) during clench, in the evaluation of right masseter at rest (p = 0.03), also the muscular activity of masseters at rest after TENS from T0 to T1 (pr = 0.04, pl = 0.04). No significant differences were found in the activity of left masseter (p = 0.41) and left temporalis (p = 0.39) during clench and MVC, in the evaluation of left masseter at rest (p = 0.57) and in the activity during MVC of right masseter (p = 0.41), left masseter (p = 0.34), right temporalis (p = 0.51) and left temporalis (p = 0.77). Results showed that the activity of the masseter and temporalis muscles increased significantly after SARPE during rest and clenching on the side where the cross-bite was treated.

Medication-Related Osteonecrosis of the Jaw in Dental Practice: A Retrospective Analysis of Data from the Milan Cohort.

A retrospective analysis was performed with the aim of understanding whether the risk factors showed in the literature for medication-related osteonecrosis of the jaws (MRONJ) in cancer patients are also relevant in osteoporotic patients taking antiresorptive drugs (ARDs). Data were retrospectively pooled from health records of patients on ARDs who requested a dental visit between January 2006 and April 2020 in the Dental Unit at Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan. A total of 434 patients were included. The following variables were collected: sex, age, smoking habit, type of ARD, duration of treatment, route of administration, therapeutic indication, concurrent systemic therapies and pathologies. Statistical analysis confirmed the relevance of chemotherapy, smoking, and immunosuppressive drugs as risk factors. In addition, a higher frequency of MRONJ in osteoporotic patients was reported in our cohort in association with an immunodeficiency disorder of variable origin. In conclusion, the identification of individual risk-profile before dental treatments is crucial for prevention. Anamnesis should include main risk factors, such as immunosuppression, dental extractions, smoking, trauma, and poor dental health. Nevertheless, our suggestion for dental professionals is to conduct a complete medical history of patients who mention long-term per oral therapies with ARDs for osteoporosis. Osteoporotic, as well as cancer patients, may also benefit from periodic monitoring of the ARDs therapy in order to prevent MRONJ.

Post-Operative Patients' Satisfaction and Quality of Life Assessment in Adult Patients with Obstructive Sleep Apnea Syndrome (OSAS).

BACKGROUND: The treatment for severe OSAS includes maxillomandibular advancement surgical option in selected cases. The aim of this study was to evaluate the post-operative impact of bimaxillary surgery on satisfaction and consequently the quality of life of these patients. METHODS: This study included 18 patients with severe OSAS who received maxillomandibular advancement surgery. Patients were divided into Group A (operated by CAD/CAM) and Group B (conventional surgery). The impact of bimaxillary surgery on satisfaction and quality of life of these patients was evaluated by utilizing post-operative life quality and Rustemeyer's patient-satisfaction-based survey. RESULTS: A total of 18 adult OSAS patients (Group A: 11 patients, Group B: 7 patients) with a mean age of 44.39 years (SD ± 9.43) were included. Mean follow-up period was 32.64 months (SD ± 21.91). No intra-operative complications were seen in any patients. Post-operative complication was seen in one patient and the mandible did not integrate. According to the results, overall post-operative satisfaction score was 79.72% (SD ± 9.96). There was no significant difference among those in Group A and Group B. CONCLUSIONS: Maxillomandibular advancement surgery seems to be beneficial in terms of patients' satisfaction in severe adult OSAS patients and can be considered as a valuable option in selected cases.

Accuracy of splint vs splintless technique for virtually planned orthognathic surgery: A voxel-based three-dimensional analysis.

PURPOSE: This study compared two transferring methods for virtually planned orthognathic surgery - the CAD/CAM intermediate splint and the customized surgical guide with fixation plates. METHODS: This was a prospective clinical study in which participants were consecutively recruited and underwent bimaxillary orthognathic surgery. They were divided into two groups based on the transferring method used. The pre- and postoperative CBCTs were aligned using voxel-based landmark-free registration, and the discrepancies for selected points were compared with the planned displacement of the virtually planned surgery. The maxilla and mandible were analyzed separately, and translation and rotation movements were considered. RESULTS: A total of 16 patients, divided into two groups of eight patients each, were included in this study. The splintless group was significantly more accurate for the translation movement along the x-axes for points A (p = 0.008; mean absolute error 0.527 ± 0.387 for the splint group and 0.137 ± 0.067 for the splintless group) and Ans (p = 0.045; mean absolute error 0.535 ± 0.446 for the splint group and 0.156 ± 0.002 for the splintless group). For the mandible there was a significant difference in accuracy along the x-axes for points B (p = 0.049; mean absolute errors 1.728 ± 1.181 and 0.697 ± 0.519 for the splint and splintless groups, respectively), LL3 (p = 0.049; mean absolute error 1.629 ± 0.912 and 0.851 ± 0.797 for the splint and splintless groups, respectively), LR3 (p = 0.049; mean absolute error 1.711 ± 0.906 and 0.844 ± 0.780 for the splint and splintless groups, respectively), with the splintless group being more accurate. For the rotation the splintless group was significantly more accurate along the y-axes (p = 0.04; mean absolute error 1.62 ± 0.78 and 0.49 ± 0.31 for the splint and splintless groups, respectively) and z-axes (p = 0.04; mean absolute error 0.63 ± 0.45 and 0.17 ± 0.05 for the splint and splintless groups, respectively) for the maxilla, while no significant difference was found for the mandible. CONCLUSIONS: Overall, the customized fixation plate system is more accurate than the intermediate CAD/CAM splint for transferring the virtual plan into the operation room.

Photobiomodulation and Miescher's cheilitis granulomatosa: case report.

BACKGROUND: Miescher's cheilitis granulomatosa (MCG) is a rare chronic inflammatory disease and is known as the monosymptomatic clinical form of Melkersson-Rosenthal syndrome (MRS). It is characterised by swelling of one or both lips and more frequently affects the upper lip. Histopathological findings show the presence of numerous inflammatory infiltrates and granuloma formations. Pharmacological treatments and surgery have provided results that are positive yet insufficiently stable in the long term. The clinical case described is of a 68-year-old female patient with a diagnosis of MCG of the upper lip. CASE PRESENTATION: The patient was diagnosed and treated at the Oral Medicine and Oral Pathology outpatient clinic of Maxillofacial and Odontostomatology Unit, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico. The patient was recommended localised treatments of photobiomodulation (PBM) using a diode laser with a 635 nm and 980 nm dual-wavelength (λ) approach, a 600-micron fibre, and a handpiece with a 1-cm-diameter lens at 300 mW. Three treatments a week were administered for four weeks for a total of 12 treatment sessions (T 1-T 12). After that, the patient had a long follow-up period of about 2 years. The therapeutic results were clear from the initial stages of treatment. There was an immediate, gradual, and consistent reduction in labial swelling. A reduction in the size of the lip by about 35% at T 10-T 12 was observed, returning the size and volume of the upper lip within the normal clinical range. The painful symptoms subsided after the seventh treatment (T 7). The histopathological check at 3 months and the follow-up in particular confirmed the disease was in remission with satisfactorily stable treatment results. Moreover, the patient did not use any other treatments on the area from the early laser treatments through to the end of the follow-up period. CONCLUSIONS: Our experience describes a clinical case of MCG treated with PBM and effectively resolved with a reduction of the lip swelling. The real success of the treatment emerged over time, showing that the tissue healing was stable. In absence of any collateral phenomena, this confirms the effective and documented therapeutic potential of PBM for chronic inflammatory infiltrates.

Dental implant-based oral rehabilitation in patients reconstructed with free fibula flaps: Clinical study with a follow-up 3 to 6 years.

BACKGROUND: Oral rehabilitation of patients after maxillofacial reconstructive surgery represents a challenge and stable prosthetic retention can be achieved with the use of dental implants. PURPOSE: This retrospective report aimed to evaluate implant-based oral rehabilitation following maxillofacial reconstruction with free fibula flaps. MATERIALS AND METHODS: A total of 14 patients who had reconstruction with fibula flaps either by CAD/CAM or conventional surgery were included in this study. A total of 56 implants (40 in flaps, 16 in native bone) were evaluated. Follow-up after reconstructive surgery ranged between 3.25 and 6.3 years. Follow-up after implant surgery ranged between 1.5 and 3.8 years. RESULTS: Overall survival rate was 85.7% in free fibula flaps and 85.6% in dental implants. Eight implants were lost in three patients and all of these failures were in dental implants inserted in free flaps. According to the results on patient basis, the implant survival was not influenced by any variable. CONCLUSIONS: The maxillofacial reconstruction with free fibula flap and oral rehabilitation with implant-supported prostheses after ablative surgery can be considered as an effective and safe procedure with successful aesthetic and functional outcomes.

The Effect of Orthognathic Surgery on Soft-Tissue Facial Asymmetry: A Longitudinal Three-Dimensional Analysis.

In modern orthognathic surgery, the functional results cannot disregard a good aesthetic outcome. In this study, a stereophotogrammetric longitudinal analysis of the symmetry of facial thirds was performed in 18 patients affected by Class III skeletal malocclusion, with clinical asymmetry, treated with a bimaxillary osteotomy. Their 3-dimensional facial images were acquired in the preoperative phase and 6, 12, and 24 months after surgery, and compared to those obtained in a control group of 23 subjects with Class I skeletal occlusion, without clinical asymmetry and no history of traumas or alterations at the maxillo-facial area. Images of the hemi-faces of the subjects were divided into thirds (upper, middle, lower), mirrored and superimposed to their contralateral ones; soft-tissue facial symmetry was obtained as the root mean square distance between the hemi-faces in the three thirds.In patients, no significant differences in facial symmetry (root mean square distance) were found among the study time points (analysis of variance, P > 0.05); the lower facial third was more asymmetric than the upper one (Tukey honestly significant difference P < 0.05). Patients were significantly more asymmetric than the control subjects (Student t, P < 0.05). In conclusion, patients with Class III malocclusion exhibited a higher level of facial asymmetry than control subjects; their asymmetry did not change significantly in the different phases of the surgical and orthodontic treatment and throughout a 24-month follow-up. In skeletal Class III patients, bimaxillary osteotomy did not modify the level of asymmetry in any facial third.

Role of Axial Split Osteotomy of Free Fibula Flap in Mandibular Reconstruction and Dental Rehabilitation.

The fibula free flap (FFF) is regarded as the gold standard in mandibular reconstruction. Dental rehabilitation is important to improve the health-related quality of life of patients undergoing mandibular reconstruction. FFF provides adequate cortical bone osseous tissue for use in dental implantation. The application of "axial split osteotomy" via a double-barrel fibula graft may enable discrepancies between the native mandible and FFF to be avoided, thereby improving the likelihood of early and successful dental rehabilitation.

Computer-Aided Design and Computer-Aided Manufacturing Versus Conventional Free Fibula Flap Reconstruction in Benign Mandibular Lesions: An Italian Cost Analysis.

PURPOSE: The cost of computer-aided design and computer-aided manufacturing (CAD-CAM) technology has created obstacles for its widespread use despite its several advantages. This study compared the cost of CAD-CAM technology with that of the conventional freehand technique in fibula reshaping for mandibular reconstruction. MATERIALS AND METHODS: A retrospective comparative study was conducted at the Maxillofacial and Dental Unit of the Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico (Milan, Italy). The study compared 15 patients in the CAD-CAM group with 10 patients in the conventional freehand group. Only benign pathologic lesions that required at least 3 fibular segments for reconstruction were included. The consumption of resources was estimated using micro-costing analysis (activity-based costing approach). RESULTS: The CAD-CAM group included 15 patients (7 men and 8 women) with a mean age of 42.2 ± 1.5 years, and the conventional freehand group included 10 patients (4 men and 6 women) with a mean age of 40.8 ± 0.9 years. Although CAD-CAM was a statistically expensive procedure in the perioperative phase (P < .0001), no significant difference was shown in total health care costs between the 2 groups (P = .98). CONCLUSION: CAD-CAM technology had a comparable expense to the conventional freehand technique, specifically for defects requiring at least 3 fibular segments.

Accuracy of the Cone Beam Computed Tomography in the Detection of Bone Invasion in Patients with Oral Cancer: A Systematic Review.

This review article aims to analyze the diagnostic accuracy of the cone beam computed tomography (CBCT) with respect to other imaging methods in detection of bone tissue invasion by oral squamous cell carcinoma (OSCC). The review was carried out of English language studies in PubMed Search, National Library of Medicine, between 1990 and 2017. For each study, sensitivity, specificity, and positive (LR+) and negative (LR-) likelihood ratio, as well as the diagnostic accuracy, and positive and negative predictive values were calculated. Of the 62 collected articles, 7 fulfilled the inclusion criteria. Tests and respective articles included were computed tomography (CT, four studies), magnetic resonance imaging (MRI, five studies), C (two studies), single-photon emission tomography (SPECT, two studies), multi-slice computed tomography (MSCT, two studies), and panoramic radiography (PR, two studies). The analytic data show values of LR+ were 14.4 (CT), 37.9 (MRI), 27.8 (CBCT), 25.5 (SPECT), 37.0 (MSCT), 4.8 (PR), respectively. The values of LR- were 0.35 (CT), 0.24 (MRI), 0.10 (CBCT), 0.06 (SPECT), 0.31 (MSCT), and 0.36 (PR), respectively. The positive and negative predictive values for bone tissue invasion by OSCC were 90.31%-74.91% (CT), 90.63%-78.69% (MRI), 80.05%-89.83% (CBCT), 72.97%-95.53% (SPECT), 87.44%-73.74% (MSCT), and 84.245%-69.18% (PR), respectively. The level of scientific evidence available today is weak. To better define the impact of CBCT on clinical decision-making, further studies with uniform methodological approach are needed.

Berberine and Tinospora cordifolia exert a potential anticancer effect on colon cancer cells by acting on specific pathways.

Berberine (BBR) is a natural active principle with potential antitumor activity. The compound targets multiple cell signaling pathways, including proliferation, differentiation, and epithelial-mesenchymal transition. The aim of this study was to elucidate the mechanisms behind the anticancer activity of BBR by comparing the effects of purified BBR with those of the extract of Tinospora cordifolia, a medicinal plant that produces this metabolite. The expression levels of a panel of 44 selected genes in human colon adenocarcinoma (HCA-7) cell line were quantified by real-time polymerase chain reaction (PCR). BBR treatment resulted in a time- and dose-dependent down regulation of 33 genes differently involved in cell cycle, differentiation, and epithelial-mesenchymal transition. The trend was confirmed across the two types of treatment, the two time points, and the different absolute dosage of BBR. These findings suggest that the presence of BBR in T. cordifolia extract significantly contributes to its antiproliferative activity.

Non-syndromic cleft palate: Association analysis on three gene polymorphisms of the folate pathway in Asian and Italian populations.

Periconceptional folic acid supplementation can reduce the risk of inborn malformations, including orofacial clefts. Polymorphisms of MTHFR, TCN2, and CBS folate-related genes seem to modulate the risk of cleft lip with or without cleft palate (CL/P) in some populations. CL/P and cleft palate only (CPO) are different malformations that share several features and possibly etiological causes. In the present investigation, we conducted a family-based, candidate gene association study of non-syndromic CPO. Three single nucleotide polymorphisms, namely, rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were investigated in a sample that included 129 Italian and 65 Asian families. No evidence of association between the three genotyped polymorphisms and CPO was found in the Italian and Asian cases, indeed the transmission disequilibrium test did not detect any asymmetry of transmission of alleles. This investigation, although with some limitation, further supports that CL/P and CPO diverge in their genetic background.

Use of CAD-CAM technology to improve orthognathic surgery outcomes in patients with severe obstructive sleep apnoea syndrome.

INTRODUCTION: Although multilevel surgery is the mainstay treatment for severe obstructive sleep apnoea syndrome (OSAS), bi-maxillary surgery (maxillomandibular advancement [MMA]) is the most efficacious single procedure for the expansion of the whole pharyngeal airway. MMA is an alternative to the gold standard of continuous positive airway pressure and is equivalent to tracheotomy. PATIENTS AND METHOD: Computer-aided design/computer-aided manufacturing (CAD-CAM) technology was used to virtually assess the degree of mandibular and/or maxillary advancement and rotation required to obtain adequate posterior airway space (PAS) in eight patients (seven males, one female). The mean age of the patients was 45.5 years (range, 27-51 years), and the average body mass index was 28.9 kg/m2 (range, 21.9-31.8 kg/m2). RESULTS: The study group showed significant mandibular advancement, widening of the PAS, and reduction of the apnoea hypopnea index (p < 0.0001, p < 0.0001, and p < 0.0002, respectively). Moreover, patient satisfaction scores regarding postoperative facial profile changes showed excellent compliance. CONCLUSION: This study demonstrated that bi-maxillary surgery is an efficient single surgical procedure in patients with multilevel OSAS. CAD-CAM technology aided surgeons in performing this operation precisely and enabled patients to expect specific facial profiles.

Evaluation of the Accuracy of Virtual Planning in Orthognathic Surgery: A Morphometric Study.

BACKGROUND: The purpose of this study was to prospectively test the accuracy of computer-aided orthognathic surgery comparing the virtual surgical planning with the three-dimensional (3D) outcome. METHODS: Patients that underwent computer-assisted orthognathic surgery were retrospectively evaluated. The postoperative results were compared with the surgical plan, superimposing the postoperative computed tomography (CT) scan onto the virtual plan. Surface-based superimpositioning of the postoperative CT scan onto the 3D preoperative plan was carried out to visualize the discrepancy between preoperative virtual plan and postoperative 3D CT result. RESULTS: A total of 17 consecutive patients that underwent two-jaw computer-assisted orthognathic surgery were enrolled in the study.The average linear differences for selected points were <1 mm in 12 patients out of 17. In 5 patients out of 17, the average differences for selected points were <2 mm. CONCLUSIONS: An overall high degree of accuracy between the virtual plan and the postoperative result was found.

In Vitro Anticancer Activity of Extracellular Vesicles (EVs) Secreted by Gingival Mesenchymal Stromal Cells Primed with Paclitaxel.

Interdental papilla are an interesting source of mesenchymal stromal cells (GinPaMSCs), which are easy to isolate and expand in vitro. In our laboratory, GinPaMSCs were isolated, expanded, and characterized by studying their secretome before and after priming with paclitaxel (PTX). The secretome of GinPaMSCs did not affect the growth of cancer cell lines tested in vitro, whereas the secretome of GinPaMSCs primed with paclitaxel (GinPaMSCs/PTX) exerted a significant anticancer effect. GinPaMSCs were able to uptake and then release paclitaxel in amounts pharmacologically effective against cancer cells, as demonstrated in vitro by the direct activity of GinPaMSCs/PTX and their secretome against both human pancreatic carcinoma and squamous carcinoma cells. PTX was associated with extracellular vesicles (EVs) secreted by cells (EVs/PTX), suggesting that PTX is incorporated into exosomes during their biogenesis. The isolation of mesenchymal stromal cells (MSCs) from gingiva is less invasive than that from other tissues (such as bone marrow and fat), and GinPaMSCs provide an optimal substrate for drug-priming to obtain EVs/PTX having anticancer activity. This research may contribute to develop new strategies of cell-mediated drug delivery by EVs that are easy to store without losing function, and could have a superior safety profile in therapy.

Donor-Site Morbidity After Osteocutaneous Free Fibula Transfer: Longitudinal Analysis of Gait Performance.

PURPOSE: The purpose was to evaluate donor-site clinical morbidity and changes in kinematic gait parameters after the harvest of a vascularized free fibula flap for facial reconstruction. MATERIALS AND METHODS: We enrolled 14 patients (aged 50 ± 15 years) in a longitudinal study. Every patient underwent a double evaluation in which a presurgical assessment and 6-month postsurgical assessment were performed. Subjective donor-site evaluation was carried out through unstructured clinical questioning about pain, paresthesia, walking ability, and restrictions in activity. Further subjective evaluations were assessed through the Western Ontario and McMaster Universities Osteoarthritis Index and the Point Evaluation System for Lower Extremity Fibulectomy. A clinical evaluation of the donor site assessed muscular deficits, sensibility disturbance, and wound healing. Temporal and spatial kinematic parameters were measured through gait analysis during overground walking at a comfortable speed. RESULTS: Postsurgical clinical examinations detected 1 patient affected by a neurologic disorder and 3 patients with donor-site pain, whereas 10 patients (71%) declared no residual alterations in the operated leg. On average, the Western Ontario and McMaster Universities Osteoarthritis Index score was 367 of 2,400, and the Point Evaluation System for Lower Extremity Fibulectomy score was 19 of 24. Presurgical versus postsurgical gait analysis comparison showed no significant differences in gait parameters except for a 6% reduction in the double-support phase. Stance values were higher for the operated limb in both evaluations (+1.3% before surgery, +1.8% after surgery). No alterations were detected in the range of motion of the lower-limb joints. CONCLUSIONS: Considering the slight modification of the gait pattern, which is not usually perceived by patients, vascularized free fibula flap harvest was generally associated with successful functional and subjective outcomes of the donor site.

Fibula free flap pedicle ossification: Experience of two centres and a review of the literature.

PURPOSE: The osteogenic potential of vascularized periosteum has been described in a few cases in the literature, and many different factors have been pointed out as plausible. Our aim was to review the literature in order to give a complete overview of this topic and to report on our clinical experience. PATIENTS & METHODS: Our experience includes three patients who underwent maxillectomy and FFF reconstruction. A progressive reduction in mouth opening was noticed in the months after surgery, and CT scans showed calcified tissue around the pedicle. Surgical revisions were performed. No recurrences were noticed. A full systematic literature review was conducted, including studies published on or before September 2016. RESULTS: Clinically, free flap pedicle ossification is presented as trismus, hard swelling, and severe pain during movements, although the diagnosis is scarce and often fortuitous. From January 2010 to January 2016 we performed 68 FFF reconstructions, and the incidence of FFF pedicle ossification in our experience was 4.4%. CONCLUSION: Ossification of FFF pedicle is uncommon, but when it occurs, it has dramatic clinical consequences. Follow-up CT scan can be useful in diagnosis. In our experience, surgery should be performed only when the patient is symptomatic.