Are Cellular Bone Matrix Allografts a Viable Option for Mandibular Tissue Engineering and Reconstruction?

BACKGROUND: Traditional mandibular reconstruction has relied on the use of vascularized and non-vascularized autografts. The use of allografts and tissue engineering modalities has risen as an alternative. PURPOSE: The purpose of this study was to determine the success of a cellular bone matrix (CBM) allograft composed of lineage committed bone forming cells for mandibular tissue engineering and reconstruction. STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study was implemented using data from subjects treated with a CBM at the University of Louisville from 2019 to 2023. Subjects were excluded if they were not treated with a CBM, data were not complete, or postoperative follow-up time was less than 3 months. PREDICTOR VARIABLES: The predictor variables were composed of heterogenous variables grouped into the following categories: demographics (age, sex), medical history (history of penicillin [PCN] allergy, history of diabetes mellitus [DM] and tobacco use), etiology (benign tumor, ballistic trauma, nonballistic trauma, odontogenic cyst, osteomyelitis/ medication-related osteonecrosis of the jaw), mandibular resection length (cm) and type (marginal, segmental), delayed versus immediate reconstruction, and whether an autograft (proximal tibia) with platelet-rich fibrin was used in combination with the CBM. MAIN OUTCOME VARIABLE: The primary outcome variable was graft success (yes or no). Success was defined as bony union and defect fill (demonstrated on panoramic radiograph) and mandibular stability (based on postoperative clinical examination at 3 months). COVARIATES: Not applicable. ANALYSES: Descriptive statistics were calculated for each variable. To measure the associations between the risk factors and graft success, Fisher's exact test for categorical variables and the Wilcoxon rank sum test for numeric data were used. A P value of <.05 was considered significant. RESULTS: The sample included 38 subjects. The median age of all subjects was 46 (interquartile range 32.6) years. Overall, 28 (73.7%) cases were successful. Subjects with a reported PCN allergy or a history of DM had significantly lower success (2, 7.1% with PCN allergy or DM) compared to those who did not (P = .008, PCN allergy; P = .03, DM). CONCLUSIONS AND RELEVANCE: This is the largest case series of CBM based mandibular reconstruction relative to the available maxillofacial surgery literature. The clinician should consider confirmation of PCN allergy so PCN-type antibiotics can be used. CBMs may be an alternative to autografts.

Can a Point-of-Care 3D Printing Workflow Produce Accurate and Successful Results for Craniomaxillofacial Trauma?

BACKGROUND: Computer-aided design and manufacturing (CAD/CAM) is having a profound impact on craniomaxillofacial surgery, and point-of-care (POC) solutions for repairing facial trauma are starting to emerge. PURPOSE: The purpose of this study was to demonstrate the success and accuracy of a POC 3D printing workflow for craniomaxillofacial trauma. STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study was undertaken to analyze subjects presenting to a level 1 trauma center after sustaining facial trauma and were then treated using the POC 3D printing workflow. Subjects were excluded if they were not treated with the POC 3D printing workflow, were lost to follow-up, or if clinical data were incomplete. PREDICTOR VARIABLE: Predictor variables included the cause of trauma (mechanism), location of the mandibular fracture, type of fracture, mandibular severity score, and repair error (ie, root mean square error (RMSE) value for planned vs actual outcome). MAIN OUTCOME VARIABLE(S): The primary outcome variables were case success and case error. Success was defined as clinical and radiographic evidence of bony stability at 3 months. Case accuracy was calculated overlaying preoperative plan data to postoperative data generating a numerical value (RMSE value, mm). COVARIATES: Covariates included age (years), gender (male/female), surgery time (mins), and CAD/CAM time (preoperative). ANALYSES: Descriptive statistics were calculated for each variable. Dependence between rates or counts was established using the Wilcoxon rank sum or Fisher's exact test. Linear regression model was computed to discern how predictor variables influence RMSE. A P value < .05 was considered statistically significant. RESULTS: The sample included 27 subjects (19 male/8 female). The average age of all subjects was 46.4 ± 18.0 years. Common mechanisms of injury were assault (33%) and self-inflicted gunshots (SIGSW; 30%), and the average severity score for mandible injury was (13.5 ± 3.3). Ninety-three percent of cases were deemed successful. The average repair accuracy (RMSE value) was 3.4 ± 1.8 mm. A linear regression model indicated those injured by a fall (ß-coefficient 1.99; P = .010), motor vehicle collision (ß-coefficient 1.49; P = .043), or SIGSW (ß-coefficient 2.82; P < .001) correlated with RMSE. CONCLUSION AND RELEVANCE: In-house CAD/CAM technologies can be utilized at the POC to repair complex facial trauma accurately and successfully.

Intermaxillary Fixation in the Primary and Mixed Dentition.

Anatomic differences of the primary dentition may hinder traditional methods of intermaxillary fixation. Furthermore, the presence of both the primary and permanent dentition can complicate establishing, and maintaining, the preinjury occlusion. The treating surgeon must be aware of these differences for optimal treatment outcomes. This article discusses and illustrates methods that facial trauma surgeons can use to establish intermaxillary fixation in children aged 12 years and younger.

Anatomical Location of Initial and Repeat Mandible Fractures: A 5-Year, Multi-Institution Retrospective Study.

PURPOSE: The purpose of the present study was to investigate new fracture patterns resulting from low velocity mechanisms in subjects who had previously fractured their mandible and had been treated with open reduction and internal fixation (ORIF) or closed reduction. METHODS AND MATERIALS: A multi-institutional retrospective cohort study was designed to analyze subjects presenting at 2 tertiary care centers with mandibular fractures with specific interest in subjects who had repeat mandible fractures. Variables recorded included demographic (age, sex, etc) data, fracture location of all fractures treated, and the location of previous fracture. Descriptive and bivariate analyses were completed of the data. RESULTS: The sample included a total of 492 subjects and 875 total fractures from both institutions. Four hundred fourty-four (91.1%) were male. The average age of all subjects was 36.4 ± 14.9 years. Twenty-six (5.28%) subjects were previously treated for a mandible fracture. All subjects' subsequent fractures occurred outside of previous ORIF except for 1 subject. Original fracture location (P = .596) and previous ORIF type (P = .689) did not influence if the subsequent fracture was within a site of previous ORIF. CONCLUSIONS: The present study demonstrates that repeat mandible fractures are relatively rare, likely to occur only 5% of the time at large tertiary care centers. The repeat fracture is not likely to occur in a site of previous ORIF, regardless of the ORIF modality. Furthermore, the fracture is likely to occur on the contralateral side. This is 1 of the largest data sets on repeat mandible fractures, which, given their rarity, are difficult to study.

Immediate Reconstruction of Segmental Mandibular Defects With Nonvascular Bone Grafts: A 30-Year Perspective.

PURPOSE: The use of nonvascular bone grafts for immediate mandibular reconstruction has remained a controversial topic. The purpose of the present study was to investigate the variables that might influence graft survival examining the outcomes from 30 years of experience. MATERIALS AND METHODS: We designed a retrospective cohort study to analyze the data from patients at a tertiary university medical center who had undergone segmental mandibular resection with immediate reconstruction with a nonvascularized free bone graft with or without adjuncts from 1989 to 2019. The predictor variables recorded included general demographic data, pathologic diagnosis, resection length, reconstruction modality, bone graft type, and inferior alveolar nerve procedures. The primary outcome variable was graft success, defined as bony union demonstrated on panoramic radiographs and mandibular stability demonstrated on clinical examination at 4 months postoperatively. Descriptive, bivariate, and linear regression models were computed. RESULTS: The sample included 47 subjects with a mean age of 43 ± 16 years; 51.1% were men. Of the 47 patients, 25 had a tissue diagnosis of benign tumor, most of which were ameloblastoma (n = 16) or ossifying fibroma (n = 6), and 22 had a tissue diagnosis of osteomyelitis or medication-related osteonecrosis of the jaw (MRONJ). The average resection size for all the patients was 6.9 ± 2.5 cm and was 6.1 ± 1.5 cm for those with a benign tumor and 7.8 ± 3.1 cm for those with osteomyelitis or MRONJ. The mean defect size of grafts that failed was 10.7 ± 3.5 cm and 6.5 ± 2.0 cm for those that succeeded (P ≤ .001). A linear regression model revealed that graft length correlated significantly with graft outcome (ß-coefficient, -0.548; 95% confidence interval, 0.905 to 1.542; P ≤ .001). CONCLUSIONS: The results of our study have shown that nonvascular bone grafts can be used to immediately reconstruct mandibular defects greater than 6 cm from benign pathologic lesions; however, larger grafts are more likely to fail.

Are Psychiatric History and Substance Use Predictors of Mortality in Self-Inflicted Gunshot Wounds to the Face?

PURPOSE: Self-inflicted gunshot wounds to the face are one of the most challenging clinical scenarios encountered by oral and maxillofacial surgeons. Knowledge is lacking regarding which factors might influence survival after these devastating injuries, especially pertaining to psychiatric history and substance use. The purpose of the present study was to evaluate the risk factors that might influence the survival of subjects with self-inflicted gunshot wounds to the face. MATERIALS AND METHODS: A retrospective cohort study was designed to analyze the data from subjects presenting to the University of Louisville Trauma Center with self-inflicted gunshot wounds to the face from February 2010 to September 2019. The predictor variables included demographic (eg, age, gender, race), medical and psychiatric history, and toxicology test results. The primary outcome variable was death before hospital discharge. Descriptive, bivariate, and logistic regression models were computed. RESULTS: The sample included 120 subjects, with an age range of 16 to 85 years old (average age, 43.5 years); 90.8% were male, and 56.7% had survived their suicide attempt. Of the 120 patients, 35% had a history of depression, 23.3% tested positive for benzodiazepines, and 33% had a social history positive for smoking, alcohol use, and/or drug use. Depression was the single largest predictor of mortality. Patients with depression were significantly more likely to survive their injuries than were patients without depression (odds ratio, 0.230; P = .003). The presence of benzodiazepines in toxicology tests was also a significant predictor of mortality (odds ratio, 0.297; P = .018); patients testing positive were more likely to survive than were patients with negative test results or positive test results for other drugs. CONCLUSIONS: Subjects who attempt suicide via self-inflicted gunshot wounds to the face were more likely to survive their injury if they had a reported history of depression or test results positive for a benzodiazepine.

In-House Digital Workflow for the Management of Acute Mandible Fractures.

Computer-aided design and additive manufacturing are revolutionizing oral and maxillofacial surgery. Current methods use virtual surgical planning sessions and custom plate milling via third-party vendors, which is costly and time-consuming, negating the effectiveness in acute facial trauma. This technical note describes a state-of-the-art in-house expedited digital workflow for computer-aided virtual fracture reduction, 3-dimensional printing, and preoperative reconstruction plate adaptation for the management of an acute mandible fracture. This process uses the computed tomographic scan a patient receives in the emergency department or clinic. The DICOM (Digital Imaging and Communications in Medicine) data are transferred into US Food and Drug Administration-approved software, in which the fracture is segmented and virtually reduced based on condylar position, midline symmetries, and occlusion if present. The reduced mandible is then printed, which serves as a template for preoperative reconstruction plate adaptation. This method facilitates a virtually reduced fractured mandible, 3-dimensionally printed model, and ideally adapted plates ready for sterilization before surgery within 2 hours after DICOM upload.

Management of Mandibular Osteomyelitis With Segmental Resection, Nerve Preservation, and Immediate Reconstruction.

PURPOSE: The purpose was to present our experience with management of mandibular osteomyelitis with segmental resection, nerve preservation, and immediate reconstruction with nonvascularized bone grafts. PATIENTS AND METHODS: We completed a retrospective analysis of 18 cases overseen by a single practitioner at a university medical center from June 2011 to July 2018. All patients had osteomyelitis and were treated with segmental mandibular resection, inferior alveolar nerve (IAN) preservation, and immediate reconstruction with autogenous bone graft from the tibia. Data obtained from medical records included the chief complaint at initial presentation, resection size, and IAN neurosensory recovery at 6 months, as well as descriptive statistics of the patient cohort. The university institutional review board granted this study exempt status. RESULTS: The patient cohort had a mean age of 50.9 years, ranging from 29 to 70 years, and included 11 female and 7 male patients. The mean follow-up time was 15 months. The most common chief complaint at initial presentation was pathologic fracture (39%), followed closely by abscess (33%). The average mandibular resection size of all patients was 8.1 cm (standard deviation [SD], 3.3 cm). The resection size measured 7.1 cm (SD, 2.6 cm) in patients with successful bone grafts (n = 15) and 13.1 cm (SD, 2.0 cm, P = .0016) in those with graft failure (n = 3). IAN neurosensory testing showed that 54% of patients had no meaningful recovery at 6 months, 25% had partial recovery, and 21% had full recovery. Finally, osteomyelitis was eliminated in all patients. CONCLUSIONS: Segmental mandibular resection is an effective method for eradicating mandibular osteomyelitis. Furthermore, immediate reconstruction via nonvascularized grafts is successful in cases with large defects, with a mean defect size of 7.1 ± 2.6 cm. However, IAN-sparing surgery is not effective for preserving patient IAN function. Taken together, our findings show that mandibular resection with immediate reconstruction is a viable method in the treatment of mandibular osteomyelitis. This method removes infection and shortens the disease course.

Aggressive histologic features do not predict biologic behavior in melanotic neuroectodermal tumor of infancy.

While generally benign, occasional aggressive histologic features in the melanotic neuroectodermal tumor of infancy (MNTI) have been used to justify a diagnosis of malignancy; this could lead to overtreatment. We report a case with presumed aggressive histologic features that did not recur following conservative treatment. This adds evidence that histologic features are not predictive of clinical behavior in MNTI.

Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF164.

Clinical trials of therapeutic angiogenesis by vascular endothelial growth factor (VEGF) gene delivery failed to show efficacy. Major challenges include the need to precisely control in vivo distribution of growth factor dose and duration of expression. Recombinant VEGF protein delivery could overcome these issues, but rapid in vivo clearance prevents the stabilization of induced angiogenesis. Here, we developed an optimized fibrin platform for controlled delivery of recombinant VEGF, to robustly induce normal, stable, and functional angiogenesis. Murine VEGF164 was fused to a sequence derived from α2-plasmin inhibitor (α2-PI1-8) that is a substrate for the coagulation factor fXIIIa, to allow its covalent cross-linking into fibrin hydrogels and release only by enzymatic cleavage. An α2-PI1-8-fused variant of the fibrinolysis inhibitor aprotinin was used to control the hydrogel degradation rate, which determines both the duration and effective dose of factor release. An optimized aprotinin-α2-PI1-8 concentration ensured ideal degradation over 4 wk. Under these conditions, fibrin-α2-PI1-8-VEGF164 allowed exquisitely dose-dependent angiogenesis: concentrations ≥25 µg/mL caused widespread aberrant vascular structures, but a 500-fold concentration range (0.01-5.0 µg/mL) induced exclusively normal, mature, nonleaky, and perfused capillaries, which were stable after 3 mo. Optimized delivery of fibrin-α2-PI1-8-VEGF164 was therapeutically effective both in ischemic hind limb and wound-healing models, significantly improving angiogenesis, tissue perfusion, and healing rate. In conclusion, this optimized platform ensured (i) controlled and highly tunable delivery of VEGF protein in ischemic tissue and (ii) stable and functional angiogenesis without introducing genetic material and with a limited and controllable duration of treatment. These findings suggest a strategy to improve safety and efficacy of therapeutic angiogenesis.

Long-term biostability and bioactivity of "fibrin linked" VEGF121in vitro and in vivo.

Despite major advances in understanding angiogenesis over the last few years, the ability to induce angiogenesis in ischemic wounds or larger tissue-engineering constructs remains elusive. Serious risks and limited control over dose, duration, and localization of growth factor delivery make materials-based approaches viable alternatives. In an effort to minimize passive diffusion and control the release profile of delivered growth factors, matrix properties have been engineered with regard to pore size, growth factor affinity or stable growth factor binding. Recently, fibrin or biomimetic hydrogels have been engineered towards the covalent immobilization of vascular endothelial growth factor (VEGF). Most of the studies pertaining to VEGF delivery by fibrin gel constructs have focused on characterizing release profiles, receptor activation, and the angiogenic response in vitro and in vivo. Herein we demonstrate that gels containing covalently-linked VEGF (α2PI1-8-VEGF121), compared to diffusible VEGF, elicit stronger and longer-lasting angiogenic responses in subcutaneous implants of mice. This superior angiogenic response was due to both the sustained release and significant retention of bioactivity (80%) of the delivered engineered VEGF over a 12-day period. To the best of our knowledge, this is the first report to characterize long-term matrix liberated α2PI1-8-VEGF121 bioactivity, important for future efforts in angiogenesis research.