A Preclinical Trial Protocol Using an Ovine Model to Assess Scaffold Implant Biomaterials for Repair of Critical-Sized Mandibular Defects.

The present work describes a preclinical trial (in silico, in vivo and in vitro) protocol to assess the biomechanical performance and osteogenic capability of 3D-printed polymeric scaffolds implants used to repair partial defects in a sheep mandible. The protocol spans multiple steps of the medical device development pipeline, including initial concept design of the scaffold implant, digital twin in silico finite element modeling, manufacturing of the device prototype, in vivo device implantation, and in vitro laboratory mechanical testing. First, a patient-specific one-body scaffold implant used for reconstructing a critical-sized defect along the lower border of the sheep mandible ramus was designed using on computed-tomographic (CT) imagery and computer-aided design software. Next, the biomechanical performance of the implant was predicted numerically by simulating physiological load conditions in a digital twin in silico finite element model of the sheep mandible. This allowed for possible redesigning of the implant prior to commencing in vivo experimentation. Then, two types of polymeric biomaterials were used to manufacture the mandibular scaffold implants: poly ether ether ketone (PEEK) and poly ether ketone (PEK) printed with fused deposition modeling (FDM) and selective laser sintering (SLS), respectively. Then, after being implanted for 13 weeks in vivo, the implant and surrounding bone tissue was harvested and microCT scanned to visualize and quantify neo-tissue formation in the porous space of the scaffold. Finally, the implant and local bone tissue was assessed by in vitro laboratory mechanical testing to quantify the osteointegration. The protocol consists of six component procedures: (i) scaffold design and finite element analysis to predict its biomechanical response, (ii) scaffold fabrication with FDM and SLS 3D printing, (iii) surface treatment of the scaffold with plasma immersion ion implantation (PIII) techniques, (iv) ovine mandibular implantation, (v) postoperative sheep recovery, euthanasia, and harvesting of the scaffold and surrounding host bone, microCT scanning, and (vi) in vitro laboratory mechanical tests of the harvested scaffolds. The results of microCT imagery and 3-point mechanical bend testing demonstrate that PIII-SLS-PEK is a promising biomaterial for the manufacturing of scaffold implants to enhance the bone-scaffold contact and bone ingrowth in porous scaffold implants. MicroCT images of the harvested implant and surrounding bone tissue showed encouraging new bone growth at the scaffold-bone interface and inside the porous network of the lattice structure of the SLS-PEK scaffolds.

A Comparison of In Vivo Bone Tissue Generation Using Calcium Phosphate Bone Substitutes in a Novel 3D Printed Four-Chamber Periosteal Bioreactor.

Autologous bone replacement remains the preferred treatment for segmental defects of the mandible; however, it cannot replicate complex facial geometry and causes donor site morbidity. Bone tissue engineering has the potential to overcome these limitations. Various commercially available calcium phosphate-based bone substitutes (Novabone®, BioOss®, and Zengro®) are commonly used in dentistry for small bone defects around teeth and implants. However, their role in ectopic bone formation, which can later be applied as vascularized graft in a bone defect, is yet to be explored. Here, we compare the above-mentioned bone substitutes with autologous bone with the aim of selecting one for future studies of segmental mandibular repair. Six female sheep, aged 7-8 years, were implanted with 40 mm long four-chambered polyether ether ketone (PEEK) bioreactors prepared using additive manufacturing followed by plasma immersion ion implantation (PIII) to improve hydrophilicity and bioactivity. Each bioreactor was wrapped with vascularized scapular periosteum and the chambers were filled with autologous bone graft, Novabone®, BioOss®, and Zengro®, respectively. The bioreactors were implanted within a subscapular muscle pocket for either 8 weeks (two sheep), 10 weeks (two sheep), or 12 weeks (two sheep), after which they were removed and assessed by microCT and routine histology. Moderate bone formation was observed in autologous bone grafts, while low bone formation was observed in the BioOss® and Zengro® chambers. No bone formation was observed in the Novabone® chambers. Although the BioOss® and Zengro® chambers contained relatively small amounts of bone, endochondral ossification and retained hydroxyapatite suggest their potential in new bone formation in an ectopic site if a consistent supply of progenitor cells and/or growth factors can be ensured over a longer duration.

Ex Vivo Preservation of Ovine Periosteum Using a Perfusion Bioreactor System.

Periosteum is a highly vascularized membrane lining the surface of bones. It plays essential roles in bone repair following injury and reconstruction following invasive surgeries. To broaden the use of periosteum, including for augmenting in vitro bone engineering and/or in vivo bone repair, we have developed an ex vivo perfusion bioreactor system to maintain the cellular viability and metabolism of surgically resected periosteal flaps. Each specimen was placed in a 3D printed bioreactor connected to a peristaltic pump designed for the optimal flow rates of tissue perfusate. Nutrients and oxygen were perfused via the periosteal arteries to mimic physiological conditions. Biochemical assays and histological staining indicate component cell viability after perfusion for almost 4 weeks. Our work provides the proof-of-concept of ex vivo periosteum perfusion for long-term tissue preservation, paving the way for innovative bone engineering approaches that use autotransplanted periosteum to enhance in vivo bone repair.

Expanding the digital workflow for a prefabricated prelaminated fibula flap: A dental technique.

The workflow for a prefabricated prelaminated fibula free flap has been almost entirely digitized. One of the last 2 remaining steps is the impression making in stage 1 surgery. This article describes a novel computed-tomography based digital scanning technique with an assessment of the resultant accuracy.

Occlusal comparison of hand-articulation versus digital articulation in orthognathic surgery.

The aim of the present study was to develop measurement methods to evaluate occlusal differences in digitally-articulated and hand-articulated models in final occlusal planning for orthognathic surgery. A total of 10 (five class II and five class III) previously treated orthognathic cases were analysed by three oral and maxillofacial surgeon investigators, creating a total of thirty cases. Investigators used physical models to create a preferred hand-held final occlusion, which were then scanned and saved utilising a Trios 3® scanner (3Shape). Models were digitally disarticulated and sent back to investigators after a period of at least a month for digital articulation. Novel measurements of dental roll, pitch, and translational differences were performed by an independent engineer using Materialise 3-Matic® software. Statistical analysis was used to evaluate translational differences, the effect of deformity, and inter-investigator variation. A mean (SD) translational difference of 1.58 mm (1.14) mm was seen between the thirty digital and hard-articulated cases analysed. Minimal difference was seen in roll and pitch between hand articulation and digital articulation. A significant translational difference was seen in class III cases compared with class II (p = 0.0006) but not in roll or pitch. There was no significant difference seen between investigators related to translation (p = 0.18), roll (p = 0.09), or pitch (p = 0.17). Digital articulation yielded similar results to hand held in this pilot study. Using measurement techniques described in larger cohorts, its accuracy can be validated using currently available technology.

Primary Assessment of the Patient With Orbital Fractures Should Include Pupillary Response and Visual Acuity Changes to Detect Occult Major Ocular Injuries.

PURPOSE: Sight-threatening injuries associated with orbital fractures are of major concern to maxillofacial surgeons whom are often the first asked to assess these patients. Eliciting signs and symptoms that are predictive of these injuries would allow expedited ophthalmic consultation and appropriate management. We hypothesized that abnormal pupillary response is predictive of major ocular injuries. PATIENTS AND METHODS: A retrospective cohort study of patients with facial fractures was instituted with review of all associated ophthalmic injuries. The primary predictor variables were the presence or absence of post-traumatic ocular symptoms and signs (visual acuity change, diplopia, flashes and floaters, pain on globe movement, abnormal pupillary response, restriction of eye movement, and visual field defects). Secondary predictors were pattern of fracture and mechanism of fracture. The primary outcome variable was the presence or absence of major ocular injury assessed during formal ophthalmology consultation. Descriptive statistics were calculated as categorical values. Correlation between the presence or absence of predictors and outcome (major ocular injury) was calculated using χ2 analysis, with the significance value set at P ≤ .01. RESULTS: The study included 75 patients (25% of whom were female patients) with a mean age of 41 ± 22 years. We recorded 165 minor ocular injuries and 43 major ocular injuries. The mechanisms of injury included assault (48%, n = 36), motor vehicle accident (21%, n = 16), fall (17%, n = 13), sport (11%, n = 8), and occupational (3%, n = 2). The fracture pattern included zygomaticomaxillary (36%, n = 27), isolated orbital floor (25%, n = 19), complex (20%, n = 15), and isolated orbital nonfloor (19%, n = 14). Of the primary outcome predictors, only abnormal pupillary response (odds ratio, 36; P < .001) and subjective visual acuity changes (odds ratio, 10; P < .001) were predictive of major ocular injury. The mechanism of injury and pattern of fracture were not predictive of major ocular injury. CONCLUSIONS: During primary assessment of the patient with orbital fractures, abnormal pupillary response and subjective visual acuity changes are key predictors of occult major ocular injury.

Factors affecting incidence of dry socket: a prospective community-based study.

Dry socket, or alveolar osteitis, can occur because of the removal of teeth. No clear etiology has been acknowledged; however, numerous risk factors have been proposed and tested. We report on the results of a prospective, multicenter study of the incidence and factors affecting the occurrence of alveolar osteitis at the Royal Dental Hospital of Melbourne and Community Dental Clinics in Melbourne, Australia. Ethics approval was gained from the University of Melbourne and Dental Health Services Victoria. The data were analyzed in a descriptive fashion, and the factors affecting alveolar osteitis were assessed using logistic regression analysis. The incidence of alveolar osteitis was 2.3% of all teeth extracted, with 4.2% of all patients experiencing alveolar osteitis in a public dental setting. Multivariate analysis revealed operator experience, perioperative crown and root fractures, periodontal disease, posterior teeth, and, interestingly, the use of mental health medications to be significant independent risk factors for the development of alveolar osteitis. No alveolar osteitis was reported in patients taking antibiotics, the oral contraceptive pill, bisphosphonates, or oral steroid drugs. Smoking and extraction technique (either operative or nonoperative) were also not found to significantly affect the development of alveolar osteitis.