How AO CMF start-up research grants support your project

There is a large number of cephalometric analyzes, based on the analysis of facial points or based on radiology analyzes. Nowadays new technologies allow us to catch and analyze patients’ faces (thanks to 3D photography) and to get simple access to head CT-scans. Under those circumstances, our cephalometric analyzes should evolve in order to adapt to these features.
There has already been attempts to create 3D cephalometric analyzes based on CT-scans, but none of them were based on a dedicated software. Therefore results were impossible to reproduce. We propose to create a 3D cephalometric analysis free software for research based on CT-scans DICOM files, easy to use and available for everyone.
Our first step after the creation of the software is to plan a comparative study between “classic” radiography analysis and 3D analysis, on a cohort of 100 to 150 patients with a point to point comparison, to show that the 3D analysis is theoriticaly at least as good as the classical radiographic one.
The advantages of this new technology would be a greater precision in cephalometric outline, and so in the analysis of the patient facial lines. By analyzing a 3D volume we also intend to answer some multi-dimensional questions about the chin position, mandibular asymmetry and other complex facial skull movements.

The aim of the proposed clinical study is to change the conventional CT-based 3D virtual planning workflow for CMF tumors by developing a method for MRI-based tumor resection as well as free flap reconstructive planning. In addition the MRI-based workflow is complemented with the quantification of vascular flow in both donor and recipient site, as well as the 3D visualization of perforators. Project description: Multiple types of MRI sequences will be studied for visualizing bone and vascularization. Several MRI- sequences are known to be suitable for segmenting bone for 3D planning, these will be explored within this project. Also MR-Angiogram with flow measurements will be selected for visualizing arteries and to quantify the arterial flow, thereby determining suitability for transplantation. A workflow for MRI-based 3D surgical planning with bone cutting guides will be developed using a four-step approach. Key MRI parameters are defined (phase 1), followed by an application of selected bone and Phase Contrast-MRI sequences on healthy volunteers (phase 2).The most suitable (bone and Phase Contrast) MRI sequences will be chosen for phase 3. These protocols are validated by applying them on patients (n=10) and comparison to corresponding patients CT data, which is the gold standard. The mean deviation values between the MRI- and the CT-based models are determined by 3D comparison analysis as a primary outcome measure.Already for validation of Black Bone sequences approval has been obtained from the local medicalethical board (file number M16.198347).
Phase 4 entails examination of the clinical value during surgery and in pre-op clinical decision making,using bone cutting guides (for mandible/maxilla and fibula) designed from MRI-based models, inpatients with oral cancer who will undergo surgical treatment with free flap reconstruction. Secondary outcome measures are 1) the deviation of the actual bone cutting planes in the CMF region as well asat the bone-free flap, compared to the 3D planning and 2) the fit of the guides to the bone surface. The final result of this project is aimed to be a complete MRI based 3D virtual planning workflow including resection of the tumor and free flap reconstruction planning.

Published articles

Optimisation of three-dimensional lower jaw resection margin planning using a novel Black Bone magnetic resonance imaging protocol.
PLoS One. 2018 Apr 20;13(4):e0196059. doi: 10.1371/journal.pone.0196059. eCollection 2018.

Facial trauma is a common occurrence worldwide which can lead to a plethora of functional, cosmetic, and emotional sequelae. Proper diagnosis of the direction, extent, and displacement of facial fractures by oral surgeons using the gold standard high-resolution CT scanning is imperative to improve patient outcomes and avoid unnecessary complications. Despite the importance of accurate diagnosis, oral surgery residents often receive a variable level of CT interpretation training from a senior resident or staff in an unstructured manner. To address this inconsistency in training, this project aims to create a standardized, scalable training module called CTRead for new residents in oral and maxillofacial surgery everywhere so that they can become competent and confident when interpreting scans and presenting them to their senior residents and staff. CTRead will be a web based training module which will take a student, resident, or even staff member through the reading of a CT Facial Bones scan one step at a time. Users will be shown normal CT scans, taught how to interpret anatomy, and then taught how to identify common fractures in facial trauma patients. To test the effectiveness of CTRead, participants’ confidence level and actual interpretation skill will be assessed via a mandatory short but comprehensive survey and marked CT interpretation quiz at the beginning and end of the training module. This will allow us to gather key information users’ confidence in interpreting CT scans, and their ability to accurately diagnose traumatic fractures as they progress through the module. It is hoped that completion of CTRead will lead to a significant increase in both confidence level and actual interpretation skill level of oral surgery residents when it comes to reading CT Facial Bones scans for trauma patients.

Published articles

Mascarenhas W, Richmond D, Chiasson G. CTRead-A Revolutionary Approach to Training Residents in Computed Tomography Facial Bone Interpretation.
J Oral Maxillofac Surg. 2019 Apr 23. pii: S0278-2391(19)30447-1. doi: 10.1016/j.joms.2019.04.016. [Epub ahead of print]

Investigators: B.P. Jonker / Eppo Wolvius / Mohammad J. Mirzaali / Nasim Shahriari / Marina Vannucci / Amir Zadpoor, Erasmus Mc, Netherlands

Mandibular reconstruction is one of the most complex challenges that cranio-maxillofacial surgeons face. It has been reported that in 2020, there were around 377,000 new cases of oral cancer globally, frequently requiring resection of the mandibular bone followed by reconstructive surgery (Bray et al 2018 doi: 10.3322/caac.21492). Additionally, significant reconstruction of function is necessary for benign tumors, osteomyelitis, osteoradionecrosis, and extensive trauma.

Common mandibular reconstruction surgery techniques include free vascularized osteocutaneous flaps fixated with regular, pre-bend or patient specific plates. These procedures are invasive operations that often lead to considerable donor site morbidity, chronic pain, infection, and does not always yield optimal functional or aesthetic results. Additionally, the use of conventional plates without bone graft is often associated with complications such as screw loosening, plate exposure, and plate fracture (Seol et al. 2014 doi: 10.5125/jkaoms.2014.40.6.266 ). Recently, implantable solutions such as patient specific cages and scaffolds have been explored and have shown promising results in improving surgical techniques in mandibular reconstruction and might prevent the need for a free vascularized osteocutaneous flap.

Meta-biomaterials with their distinct mechanical and biological properties, are a promising method to address all the above-mentioned issues in designing multifunctional implants. The unit cell type, pore size, porosity percentage, and the distribution order of the defined unit cells throughout the implant can tune the mechanical and biological properties of the implants. This proposal, therefore, proposes the state-of-the-art hybrid design of mandibular implants using meta-biomaterials, considering the physiological loading condition of the implant to develop an implant that can withstand the loads applied while promoting cell attachment and bone growth.

In this regard, computational modeling and adaptive bone simulations will be developed to evaluate the effect of various distributions of auxetic and non-auxetic unit cells throughout the implant to optimize their strain distribution, fatigue behavior and osteoconductivity at the mandibular site in the scenario of a segmental defect obtained by surgical resection. Starting form an existing workflow to design patient specific mandibular implants, we propose to create phenomenological prediction models to evaluate bone remodeling process surrounding the implant. The two simulations would then be combined to create a computational model including both mechanical and biological behaviors surrounding a hybrid auxetic non-auxetic mandibular implant. We hypothesize that hybrid implant design can overcome the current issues with the conventional mandibular cages.

Investigators: Idan Redenski / Samer Srouji, Galilee Medical Center, Israel

While in the past 25 years, head and neck cancer has shown a decline due to prevention and early diagnosis, the incidence of oral cancer has been on a rapid rise, especially among young individuals without any known risk factors. Oral cancer and oral squamous carcinoma (OSCC) inflict more than 300,000 new cases and 145,000 deaths annually, with the aggressive nature of SCC necessitating aggressive resections of soft tissues with supporting bony framework with wide tumor-free margins. Spontaneous healing of substantial oro-facial defects, together with compromised vascular support, is unrealistic. Specifically, the adverse microenvironment created at the defect site may hinder the innate regenerative capability of the body, thus forcing external intervention by surgeons to try to repair the damaged tissues. These procedures necessitate the harvest of large, vascularized bone-containing autologous grafts.

The current state-of-the-art techniques utilize vascularized soft and hard tissue flaps, which have improved orofacial reconstruction outcomes in recent decades. However, success rates are still limited by the extent of bone tissue vascularity and lack of oral soft tissues. Autologous grafts are still associated with significant disadvantages, such as limited volume, tissue site morbidity, and substantial post-operative complications. Titanium alloys, despite excellent biocompatibility and high mechanical strength, are not biodegradable, cannot replace the missing bulk volume of bone tissue, and remain as permanent implants within the body. Moreover, these biomaterials can only bond with native bone tissue through mechanical interlocking with no bioactivity, which can result in loosening and wear, adversely affecting reconstructed soft tissues. Thus, maxillofacial surgeons and tissue engineers are confronted with the same substantial challenges in the field – creating biologically inspired, human-sized tissue replacements while minimizing the harvest of patients' tissues.

Recently, 3D-printed bone scaffolds have been experimented with to reconstruct significant defects, and different material deposition strategies have been able to recapitulate complex anatomies. Moreover, human-scaled mandibular bone was fabricated by using a tissue-engineered approach based on a biomimetic ECM-based bone matrix, harnessing the innate regenerative potential of the host's body. Still, Survival of tissue grafts at a surgical site critically depends on host capillary invasion into the tissue constructs. Laboratory-made 3D-printed engineered grafts are still discrete elements, without an arteriovenous blood supply and lacking constant connectivity with the host circulation. Despite the progress in both tissue engineering approaches and the development of new biomaterials, the lack of initial post-implantation vascularization and host-to-graft vascular connectivity is a primary cause of failure in the engraftment of bioengineered constructs.

Herein, we propose to employ accurate 3D printing to fabricate soft and hard tissue constructs, whereby a printed provisional mold will be used to manufacture engineered grafts for craniofacial rehabilitation. First, 3D printed constructs will be populated with a biomimetic hydrogel loaded with human mesenchymal and endothelial cells, which will support both vascularization and osteogenesis in vitro. Engineered grafts will be further vascularized by inducing axial vascularization, guided by a predefined architecture within constructs. Finally, the composite grafts, now in the form of soft and hard neo-tissues, will be used to rehabilitate soft and hard tissue defects in an in-vivo murine model. Achievement of this translational proof-of-concept study holds the potential to provide a solution for a clinical unmet need to reduce morbidity and improve recovery of SCC patients following resection operations.