AO CMF Start-up Grants
The call for AO CMF Start-up Grants 2021 is now closed.
AO CMF Start-up Funded Research Projects
The abstracts of the latest funded projects under the start-up grant
Project title: Creation and validation of a 3D cephalometric software based on Delaire’s analysisThere 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.
Project title: Fully MRI based 3D virtual planning of CMF tumour resection and free flap reconstruction
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.
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.
Project title: CTRead - A revolutionary approach to training residents in CT Facial Bones interpretation
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.
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]
Project title: Antibacterial nano-biomaterials for the purposes of cranio- maxillofacial surgery
Infections associated with implantable devices, also known as biomaterial associated infections (BAIs) pose a real problem in contemporary regenerative medicine and traumatology. In the head and neck area extraoral BAIs manifest as “pin sites infections” (PSI), while intraoral are known as peri-implant mucositis and/or peri-implantitis, which affects the underlying alveolar bone. Despite efforts in bioengineering to improve the biocompatibility of the metallic biomaterials, which constitute a major part of the reconstructive surgery, the problem of bacterial settlement and infection development still poses a serious threat for the treatment outcome. Along with nanotechnology evolution, antibacterial approaches with the use of different nanoparticles (NPs) were taken into concern. However, studies showed that such devices exhibited some limitations, mostly due to a restricted effective release rate, an initial burst release, cytotoxicity and unknown interactions of NPs with the host’s biomolecules. The aim of this study is twofold. First is to evaluate antibacterial activity of nano-sized zinc compounds against the bacteria responsible for infections around the biomaterials in the head and neck area. Second is to evaluate the stability of the nano-colloidal suspensions in the human and artificial saliva, and physico-chemical properties of the nano-particle-protein-sugar complexes, known as protein-coronas (PCs), in such environments which determine the activity of the NPs in the living organisms.
2019 - Pokrowiecki R, Wojnarowicz J, Zareba T, Koltsov I, Lojkowski W, Tyski S, Mielczarek A, Zawadzki P. Nanoparticles and human saliva: a step towards drug delivery systems for dental and craniofacial biomaterials. International Journal of Nanomedicine (Future Medicine). 2019:14, 9235-9257 Manuscript number NNM-2019-0189 (original article). doi: 10.2147/IJN.S221608
Pokrowiecki R. The paradigm shift for drug delivery systems for oral and maxillofacial implants. Drug Deliv. 2018 Nov;25(1):1504-1515. doi: 10.1080/10717544.2018.1477855.
Palka K, Pokrowiecki R, Krzywicka M. Chapter 13: Porous titanium materials and applications in “Titanium for Consumer Applications” Book. 1st Ed. ISBN: 9780128158203. Elsevier, 2019.
Project title: Investigating effects of BMPER on osteogenic and chondrogenic differentiationBone morphogenetic proteins (BMPs) 2 and 7 have been approved for clinical use, yet complications limit their application. In addition, the supraphysiological doses applied would indicate that their use has not yet been optimized. BMP binding endothelial regulator (BMPER) also known as Crossveinless 2 was first identified as critical mediator in vein development (Conley, Silburn et al. 2000). Today it is known that BMPER is a BMP modulator, similar to Chordin, Noggin or Gremlin and interacts with BMP 2, 4, 6, 7, 9 and 10. In humans, the syndrome Diaphanospondylodysostosis (DSD) is caused by a lack / mutation of the BMPER protein. Characteristics are absent or severely delayed ossiﬁcation of vertebral bodies and other bone defects, a short broad thorax, a short neck and respiratory insufﬁciency. The severe bone phenotype suggests that BMPER plays a major role in osteogenesis, yet it has been largely overlooked. No studies have been performed to assess whether BMPER as BMP modulator might be as osteoinductive as BMPs themselves nor whether BMPER is able to potentiate the osteoinductive effects of BMPs. The aim of our study is therefore to identify the osteogenic and chondogenic potential effects of BMPER and to establish whether BMPER is promising as a new factor for promoting bone and/ or cartilage regeneration. As a first step the effects of BMPER on MSCs (Mesenchymal stem cells) will be investigated in vitro.
Project title: Trilineage differentiation potential of periosteal cells from endochondral and intramembranous originThe periosteum is a highly vascularized bilayer membrane covering the surfaces of bone. The outer “fibrous” layer consists of fibroblasts abundant amounts of extracellular components such as collagens and elastin giving stability and elasticity to the periosteum. In contrast, the inner “cambium” layer contains progenitor cells which are crucial for bone formation and repair.
The periosteum exhibits osteogenic potential and has received considerable attention as a promising cell source for bone regeneration strategies. The high proliferation capacity and the simple availability compared to other sources of mesenchymal progenitor cells display big advantages as in vitro cell expansion is often a prerequisite for tissue engineered constructs. However, if and to which extent the harvest location affects the function of the periosteal derived cells is still unclear.
In the framework of this project we aim to compare the in vitro differentiation potential of human periosteum derived cells (hPDC) from endochondral and intramembranous origin. We hypothesize that differences in the developmental origin of the periosteum will influence the behavior and/or potency of hPDCs. We assume that due to the natural tendency for intramembranous ossification and the uniquely high bone remodeling occurring within the jaw, human JPDCs (jaw periosteal derived cells) represent a progenitor cell source with superior osteogenic properties. This would make hJPDCs more favorable for tissue engineering and regenerative medicine (TERM) of intramembranous bone.
This study is crucial for the characterization of hPDCs and can be used to guide clinical strategies that exploit periostea for tissue engineering and clinical applications. The present project may foster translational approaches for bone constructs which is of major interest for cranio-maxillofacial-, trauma- and orthopedic surgery.
Project title: Osteoinductive potential of local administration of recombinant BMP9 in the bone defects in mice systemically treated with a monoclonal RANKL antibody drugThe monoclonal antibodies against Receptor Activator for Nuclear Factor Kappa-B Ligand (RANKL) such as denosumab, are used for the antibody mediated anti-resorptive therapies (AMARTs) in patients with metastatic cancer of the bone or osteoporosis. Bone augmentation procedures in the patients having AMARTs should be carefully considered due to the risk of antiresorptive agent-related osteonecrosis of the jaw (ARONJ). Therefore, the promising bone regeneration procedure is demanded for the patients with ARONJ risk.
In the past years, BMP9 has been characterized as one of most osteogenic bone-inducers among the BMP family. Our previous in vitro and in vivo reports revealed that recombinant human (rh)BMP9 demonstrated higher osteoinductive potential when compared to rhBMP2. Furthermore, our previous preliminary data interestingly showed positive effect of rhBMP2 on bone formation in mice after anti-murine monoclonal RANKL antibody (mAb) treatment. It is hypothesized that the local administration of rhBMP9 could further promote bone regeneration in animals having AMARTS.
In this project, the recently commercially available mAb is used to create an AMART model in mice. Thereafter, rhBMP9 combined with collagen scaffold will be implanted in calvarial defects. After 4 weeks, the systemic effect of mAb and/or rhBMP9 treatment will be tested by measuring serum ALP level, TRAP-5b level and bone mineral density (BMD). The bone formation in the defects will be evaluated by microCT analysis, histomorphometry and immunohistochemical approach.
This project will show for the first time the effect of the rhBMP9 on bone regeneration potential in an AMART animal model. The results will contribute future bone regenerative therapy for the patients having AMARTS.
Project title: MRRead – A Novel Approach to Training Residents in MRI TMJ InterpretationTemporomandibular disorders (TMD) are a common occurrence worldwide which can lead to a plethora of functional and emotional sequelae. Proper diagnosis of the direction, extent, and displacement of TMJ disorders by oral surgeons using the gold standard MRI TMJ Open and Closed views 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 MRI 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 MRRead for all residents in oral and maxillofacial surgery so that they can become competent and confident when interpreting MRIs of the TMJ and presenting them to their fellow residents and staff. MRRead will be a web-based training module which will take a student, resident, or even staff member through the reading of a MRI scan one step at a time. Users will be shown normal MRI scans, taught how to interpret anatomy, and then taught how to identify common disorders in temporomandibular joints such as anterior disc displacement, joint effusion, osteoarthritis, etc. To test the effectiveness of MRRead, participants’ confidence level and actual interpretation skill will be assessed via a mandatory short but comprehensive survey and marked MRI interpretation quiz at the beginning and end of the training module. This will allow us to gather key information users’ confidence in interpreting MRI scans, and their ability to accurately diagnose traumatic fractures as they progress through the module. It is hoped that completion of MRRead will lead to a significant increase in both confidence level and actual interpretation skill level of oral surgery residents when it comes to reading MRI TMJs for patients.
Project title: Development of Virtual Reality based training in orthognathic surgery for CMF surgeonsThorough understanding of the spatial relationship of 3D anatomical structures is of paramount importance for physicians in general, and for surgeons operating on patients in particular. In craniomaxillofacial (CMF) surgery, the anatomy is complex and many important structures run in close proximity.
Nowadays, knowledge and understanding of these complex 3D shapes have to be learnt largely from images in books and screens, which lack the real 3D nature, and also do not permit interaction. It is well known that 3D interaction and immersion can contribute to a better understanding of objects around us. This accounts for all areas of the CMF surgery, but in particular for orthognathic surgery. The purpose of this project therefore, is to develop a Virtual Reality (VR)-based application that permits CMF residents to visualize and interact with facial skeleton in an immersive environment performing the LeFort I osteotomy and the bilateral sagittal split osteotomy (BSSO). More specifically, we will develop an application that allows them to: 1) provide insight in anatomical structures in the maxillary and mandibular region in a VR environment; 2) interact with these models by performing a leFort I osteotomy and a BSSO. While cutting through the bones the surgeons receive feedback from their handling via scoring. In this feedback, accuracy of the osteotomy and overall progress of handling can be reported.
There is a rapidly growing interest in the use of intelligent tools in virtual simulation of various applications for different training purposes. However, to the best of our knowledge there are none in the CMF-field. Aiming to simulate orthognathic surgery and effectively train clinicians to perform surgeries properly, we will develop in the VR-simulator for orthognathic surgery also a new tool to test the efficacy of the VR-simulator. The tool in the VR-simulator can provide the participants with real-time feedback to assist with training. The presented study aims to investigate evidence of validity of the tool while acquiring meaningful feedback regarding the potential use of the simulator and to get feedback from participants how they evaluate the use of VR in their training of orthognathic surgery.
Project Title: The Orbital Index: A Quantitative Tool for Prediction of Delayed Enophthalmos in Orbital Floor Fracture ManagementEarly identification of surgical indication is critical to optimizing outcomes in orbital floor fracture management. Delay of repair in this cohort risks persistent diplopia, persistent facial deformity, and infraorbital nerve injury. While muscle entrapment and acute globe malposition are widely accepted as absolute indications for repair, it has remained a challenge to identify those patients at risk for developing delayed enophthalmos and requiring subsequent surgery. The objective of this project is thus to validate a novel comprehensive quantitative clinically applicable prediction tool that guides orbital floor fracture management by stratifying risk for enophthalmos and establishing a threshold value for surgical intervention.