Papers by Cedryck Vaquette
Neurotrauma Reports
Neurogenic heterotopic ossifications (NHOs) are incapacitating complications of traumatic brain a... more Neurogenic heterotopic ossifications (NHOs) are incapacitating complications of traumatic brain and spinal cord injuries (SCI) that manifest as abnormal bone formation in periarticular muscles. Using a unique model of NHO after SCI in genetically unmodified mice, we have previously established that the innate immune system plays a key driving role in NHO pathogenesis. The role of adaptive immune cells in NHO pathogenesis, however, remains unexplored in this model. Here we established that B lymphocytes were reduced in the spleen and blood after SCI and increased in muscles of mice in which NHO develops, whereas minimal changes in T cell frequencies were noted. Interestingly, Rag1-/mice lacking mature T and B lymphocytes, developed NHO, similar to wildtype mice. Finally, mice that underwent splenectomy before SCI and muscle damage also developed NHO to the same extent as non-splenectomized SCI controls. Overall, our findings show that functional T and B lymphocytes have minimal influence or dispensable contributions to NHO development after experimental SCI in mice.
Scientific Reports, 2021
The anti-angiogenic effects of bisphosphonates have been hypothesized as one of the major etiolog... more The anti-angiogenic effects of bisphosphonates have been hypothesized as one of the major etiologic factors in the development of medication-related osteonecrosis of the jaw (MRONJ), a severe debilitating condition with limited treatment options. This study evaluated the potential of a gelatine-hyaluronic acid hydrogel loaded with the angiogenic growth factor, vascular endothelial growth factor (VEGF), as a local delivery system to aid in maintaining vascularization in a bisphosphonate-treated (Zoledronic Acid) rodent maxillary extraction defect. Healing was assessed four weeks after implantation of the VEGF-hydrogel into extraction sockets. Gross examination and histological assessment showed that total osteonecrosis and inflammatory infiltrate was significantly reduced in the presence of VEGF. Also, total vascularity and specifically neovascularization, was significantly improved in animals that received VEGF hydrogel. Gene expression of vascular, inflammatory and bone specific ma...
Rupture of the scapholunate interosseous ligament can cause the dissociation of scaphoid and luna... more Rupture of the scapholunate interosseous ligament can cause the dissociation of scaphoid and lunate bones, resulting in impaired wrist function. Current treatments (e.g., tendon-based surgical reconstruction, screw-based fixation, fusion, or carpectomy) may restore wrist stability, but do not address regeneration of the ruptured ligament, and may result in wrist functional limitations and osteoarthritis. Recently a novel multiphasic bone-ligament-bone scaffold was proposed, which aims to reconstruct the ruptured ligament, and which can be 3D-printed using medical-grade polycaprolactone. This scaffold is composed of a central ligament-scaffold section and features a bone attachment terminal at either end. Since the ligament-scaffold is the primary load bearing structure during physiological wrist motion, its geometry, mechanical properties, and the surgical placement of the scaffold are critical for performance optimisation. This study presents a patient-specific computational biomec...
Nanomaterials, 2021
Cells interact with 3D fibrous platform topography via a nano-scaled focal adhesion complex, and ... more Cells interact with 3D fibrous platform topography via a nano-scaled focal adhesion complex, and more research is required on how osteoblasts sense and respond to random and aligned fibers through nano-sized focal adhesions and their downstream events. The present study assessed human primary osteoblast cells’ sensing and response to random and aligned medical-grade polycaprolactone (PCL) fibrous 3D scaffolds fabricated via the melt electrowriting (MEW) technique. Cells cultured on a tissue culture plate (TCP) were used as 2D controls. Compared to 2D TCP, 3D MEW fibrous substrates led to immature vinculin focal adhesion formation and significantly reduced nuclear localization of the mechanosensor-yes-associated protein (YAP). Notably, aligned MEW fibers induced elongated cell and nucleus shape and highly activated global DNA methylation of 5-methylcytosine, 5-hydroxymethylcytosine, and N-6 methylated deoxyadenosine compared to the random fibers. Furthermore, although osteogenic mark...
Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2020
In this study, composite scaffolds based on poly(caprolactone) (PCL) and non-covalently functiona... more In this study, composite scaffolds based on poly(caprolactone) (PCL) and non-covalently functionalized few-layer graphene (FLG) were manufactured by an extrusion-based system for the first time. For that, functionalized FLG powder was obtained through the evaporation of a functionalized FLG aqueous suspension prepared from a graphite precursor. Cryomilling was shown to be an efficient mixing method, producing a homogeneous dispersion of FLG particles onto the PCL polymeric matrix. Thereafter, fused deposition modeling (FDM) was used to print 3D scaffolds and their morphology, thermal, biodegradability, mechanical, and cytotoxicity properties were analysed. The presence of functionalized FLG demonstrated to induce slight changes in the microstructure of the scaffold, did not affect the thermal stability and enhanced significantly the compressive modulus. The composite scaffolds presented a porosity of around 40% and a mean pore size in the range of 300 μm. The cell viability and proliferation of SaOs-2 cells were assessed and the results showed good cell viability and long-term proliferation onto produced composite scaffolds. Therefore, these new FLG/PCL scaffolds comprised adequate morphological, thermal, mechanical, and biological properties to be used in bone tissue regeneration.
Materials Science and Engineering: C, 2020
In order to increase the bone forming ability of MBG-PCL composite scaffold, microporosity was cr... more In order to increase the bone forming ability of MBG-PCL composite scaffold, microporosity was created in the struts of 3D-printed MBG-PCL scaffolds for the manufacturing of a construct with a multiscale porosity consisting of meso-micro-and macropores. 3D-printing imparted macroporosity while the microporosity was created by porogen removal from the struts, and the MBG particles were responsible for the mesoporosity. The scaffolds were 3Dprinted using a mixture of PCL, MBG and phosphate buffered saline (PBS) particles, subsequently leached out. Microporous-PCL (pPCL) as a negative control, microporous MBG-PCL (pMBG-PCL) and non-microporous-MBG-PCL (MBG-PCL) were investigated. Scanning electron microscopy, mercury intrusion porosimetry and micro-computed tomography demonstrated that the PBS removal resulted in the formation of micropores inside the struts with porosity of around 30% for both pPCL and pMBG-PCL, with both constructs displaying an overall porosity of 80-90%. In contrast, the MBG-PCL group had a microporosity of 6% and an overall porosity of 70%. Early mineralisation was found in the pMBG-PCL postleaching out and this resulted in the formation a more homogeneous calcium phosphate layer when using a biomimetic mineralisation assay. Mechanical properties ranged from 5 to 25 MPa for microporous and non-microporous specimens, hence microporosity was the determining factor affecting compressive properties. MC3T3-E1 metabolic activity was increased in the pMBG-PCL along with an increased production of RUNX2. Therefore, the microporosity within a 3D-printed bioceramic composite construct may result in additional physical and biological benefits.
Journal of Orthopaedic Research, 2020
This article has been accepted for publication and undergone full peer review but has not been th... more This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Materials Science and Engineering: C, 2020
Three-dimensional Mesoporous bioactive glasses (MBGs) scaffolds has been widely considered for bo... more Three-dimensional Mesoporous bioactive glasses (MBGs) scaffolds has been widely considered for bone regeneration purposes and additive manufacturing enables the fabrication of highly bioactive patientspecific constructs for bone defects. Commonly, this process is performed with the addition of polymeric binders that facilitate the printability of scaffolds. However, these additives cover the MBG particles resulting in the reduction of their osteogenic potential. The present work investigates a simple yet effective phosphate-buffered saline immersion method for achieving polyvinyl alcohol binder removal while enables the maintenance of the mesoporous structure of MBG 3D-printed scaffolds. This resulted in significantly modifying the surface of the scaffold via the spontaneous formation of a biomimetic mineralized layer which positively affected the physical and biological properties of the scaffold. The extensive surface remodeling induced by the deposition of the apatite-like layer lead to a 3-fold increase in surface area, a 5fold increase in the roughness, and 4-fold increase in the hardness of the PBS-immersed scaffolds when compared to the as-printed counterpart. The biomimetic mineralization also occurred throughout the bulk of the scaffold connecting the MBGs particles and was responsible for the maintenance of structural integrity. In vitro assays using MC3T3-E1 pre-osteoblast like cells demonstrated a significant upregulation of osteogenic-related genes for the scaffolds previously immersed in PBS when compared to the as-printed PVA-containing scaffolds. Although the pre-immersion scaffolds performed equally towards osteogenic cell differentiation, our data suggest that a short immersion in PBS of MBG scaffolds is beneficial for the osteogenic properties and might accelerate bone formation after implantation.
International Journal of Molecular Sciences, 2019
Hemoderivatives have utilized in an empirical manner, driven by clinical considerations, leading ... more Hemoderivatives have utilized in an empirical manner, driven by clinical considerations, leading to the development of a plethora of manufacturing protocols. The purpose of this study was to investigate the composition and bioactivity of four common clinical-grade hemoderivates prepared using standardised methods. Four different hemoderivatives were obtained from sheep blood and divided into two groups: A-PRF/i-PRF (fresh) and P-PRP/L-PRP (anticoagulated). Thrombus (CLOT) was used as a control. Thrombocyte quantification, growth factor composition (IGF-I, VEGF, PDGF-BB, BMP-2), cell viability, migration and mineralization assay were evaluated. Platelet recovery was superior for L-PRP followed by P-PRP. A significant cumulative release of IGF-I and PDGF-BB was noted for A-PRF and L-PRP groups at early time points. Similar release profiles of BMP-2 and VEGF were noted in all protocols. Cell viability and migration assay have demonstrated a detrimental effect when the concentration was...
Materials Science and Engineering: C, 2018
Vertical bone augmentation of the jaws is required when the height of bone is insufficient at the... more Vertical bone augmentation of the jaws is required when the height of bone is insufficient at the site of dental implant placement. In this proof of concept study, we investigated the potential of a biphasic polycaprolactone construct combined with a hyaluronic acid based hydrogel loaded with recombinant human bone morphogenetic growth factor-2 (BMP-2) for vertical bone regeneration. The biphasic scaffold consisted of an outer shell manufactured by fused deposition modelling, mimicking native cortical bone and providing mechanical and space maintenance properties essential for bone formation. Within this shell, a 90% porous melt electrospun microfibrous mesh mimicking the architecture of cancellous bone was incorporated in order to facilitate hydrogel loading and subsequent osteogenesis and angiogenesis. The in vitro performances of the biphasic construct demonstrated that BMP-2 was released in a sustained manner over several weeks and that cell viability was maintained in the hydrogel over 21 days. qRT-PCR demonstrated the upregulation of bone markers such as osteopontin, osteocalcin and collagen 1A1 at day 3 and 14 in the constructs loaded with BMP2. In vivo assessment of the biphasic scaffold was performed using a dose of 30µg of BMP-2 in a rabbit calvarial vertical bone augmentation model. The histology and micro-CT analysis of the elevated space demonstrated that the hydrogel and the presence of BMP-2 enabled bone formation. However, this was limited to the immediate vicinity of the calvarial bone. The amount of newly formed bone was relatively small which was likely due to poor vascularisation of the extraskeletal space. The utilisation of this biomimetic biphasic construct with excellent space maintenance properties can be
Advanced Healthcare Materials, 2018
the mechanical forces experienced during mastication. Periodontitis is a chronic inflammatory dis... more the mechanical forces experienced during mastication. Periodontitis is a chronic inflammatory disease initiated by an oral bacterial biofilm, which results in periodontal hard and soft tissues destruction and can lead to tooth loss. It affects 30-40% of the population [1] and the large impact and burden of this disease on individuals and the community is well recognized not only in terms of compromised quality of life, but also overall health and systemic well-being. [2] 1.1. The Unique Challenges Faced in Achieving Periodontal Regeneration The ultimate objective of periodontal treatment is regeneration of the lost tissues of the periodontium, which involves the functional reattachment of the periodontal ligament onto newly formed cementum and alveolar bone. This requires a highly coordinated spatiotemporal healing response, including cementogenesis concomitant with periodontal ligament fiber reattachment to the previously contaminated root surface, as well as bone formation within the periodontal defect (Figure 1). In addition to the challenges posed by the complex architecture of the periodontium, healing is further complicated by the avascular nature of the tooth surface, which means that all periodontal wound healing occurs by secondary intention. Furthermore, The periodontium, consisting of gingiva, periodontal ligament, cementum, and alveolar bone, is a hierarchically organized tissue whose primary role is to provide physical and mechanical support to the teeth. Severe cases of periodontitis, an inflammatory condition initiated by an oral bacterial biofilm, can lead to significant destruction of soft and hard tissues of the periodontium and result in compromised dental function and aesthetics. Although current treatment approaches can limit the progression of the disease by controlling the inflammatory aspect, complete periodontal regeneration cannot be predictably achieved. Various tissue engineering approaches are investigated for their ability to control the critical temporospatial wound healing events that are essential for achieving periodontal regeneration. This paper reviews recent progress in the field of periodontal tissue engineering with an emphasis on advanced 3D multiphasic tissue engineering constructs (TECs) and provides a critical analysis of their regenerative potential and limitations. The review also elaborates on the future of periodontal tissue engineering, including scaffold customization for individual periodontal defects, TEC's functionalization strategies for imparting enhanced bioactivity, periodontal ligament fiber guidance, and the utilization of chair-side regenerative solutions that can facilitate clinical translation.
Archives of oral biology, 2018
Decellularization aims to harness the regenerative properties of native extracellular matrix. The... more Decellularization aims to harness the regenerative properties of native extracellular matrix. The objective of this study was to evaluate different methods of decellularization of periodontal ligament cell sheets whilst maintaining their structural and biological integrity. Human periodontal ligament cell sheets were placed onto melt electrospun polycaprolactone (PCL) membranes that reinforced the cell sheets during the various decellularization protocols. These cell sheet constructs (CSCs) were decellularized under static/perfusion conditions using a) 20 mM ammonium hydroxide (NH4OH)/Triton X-100, 0.5% v/v; and b) sodium dodecyl sulfate (SDS, 0.2% v/v), both +/- DNase besides Freeze-thaw (F/T) cycling method. CSCs were assessed using a collagen quantification assay, immunostaining and scanning electron microscopy. Residual fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were assessed with Bio-plex assays. DNA removal wit...
Journal of clinical periodontology, 2018
To evaluate the effect of decellularized tissue engineered constructs on cell differentiation in ... more To evaluate the effect of decellularized tissue engineered constructs on cell differentiation in vitro and periodontal regeneration in vivo. Periodontal ligament cell (PDLC) sheets were loaded on polycaprolactone (PCL) scaffolds and then decellularized. Constructs were assessed for their effect on allogenic PDLC and mesenchymal stem cell (MSC) differentiation in vitro, as evaluated by gene expression of bone and periodontal ligament tissue markers post-seeding. Expression of MSC marker STRO-1 was assessed by immunostaining. Decellularized constructs were evaluated in a rat periodontal defect model to assess their biocompatibility and tissue integration. Microcomputed topography (μCT) and histological assessment were performed to assess the regenerative potential of the constructs at 2 and 4 weeks postoperatively. There was upregulation of bone marker gene expression by PDLCs especially on the 14th day. MSCs lacked bone markers expression, but showed increased collagen I marker expre...
Research Integrity and Peer Review, 2017
Background: Winning funding for health and medical research usually involves a lengthy applicatio... more Background: Winning funding for health and medical research usually involves a lengthy application process. With success rates under 20%, much of the time spent by 80% of applicants could have been better used on actual research. An alternative funding system that could save time is using democracy to award the most deserving researchers based on votes from the research community. We aimed to pilot how such a system could work and examine some potential biases. Methods: We used an online survey with a convenience sample of Australian researchers. Researchers were asked to name the 10 scientists currently working in Australia that they thought most deserved funding for future research. For comparison, we used recent winners from large national fellowship schemes that used traditional peer review. Results: Voting took a median of 5 min (inter-quartile range 3 to 10 min). Extrapolating to a national voting scheme, we estimate 599 working days of voting time (95% CI 490 to 728), compared with 827 working days for the current peer review system for fellowships. The gender ratio in the votes was a more equal 45:55 (female to male) compared with 34:66 in recent fellowship winners, although this could be explained by Simpson's paradox. Voters were biased towards their own institution, with an additional 1.6 votes per ballot (inter-quartile range 0.8 to 2.2) above the expected number. Respondents raised many concerns about the idea of using democracy to fund research, including vote rigging, lobbying and it becoming a popularity contest. Conclusions: This is a preliminary study of using voting that does not investigate many of the concerns about how a voting system would work. We were able to show that voting would take less time than traditional peer review and would spread the workload over many more reviewers. Further studies of alternative funding systems are needed as well as a wide discussion with the research community about potential changes.
Journal of biomedical materials research. Part B, Applied biomaterials, Jan 7, 2017
Ligament tissue rupture is a common sport injury. Although current treatment modalities can achie... more Ligament tissue rupture is a common sport injury. Although current treatment modalities can achieve appropriate reconstruction of the damaged ligament, they present significant drawbacks, mostly related to reduced tissue availability and pain associated with tissue harvesting. Stem cell based tissue regeneration combined with electrospun scaffolds represents a novel treatment method for torn ligaments. In this study, a low fiber density polycaprolactone (PCL) electrospun mesh and sheep mesenchymal stem cells (sMSCs) were used to develop tissue engineered ligament construct (TELC) in vitro. The assembly of the TELC was based on the spontaneous capacity of the cells to organize themselves into a cell sheet once seeded onto the electrospun mesh. The cell sheet matured over 4 weeks and strongly integrated with the low fiber density electrospun mesh which was subsequently processed into a ligament-like bundle and braided with two other bundles to develop the final construct. Live/dead as...
Advanced healthcare materials, 2017
Guided bone regeneration (GBR) is a surgical procedure utilizing occlusive membranes for providin... more Guided bone regeneration (GBR) is a surgical procedure utilizing occlusive membranes for providing space maintenance and enabling selective repopulation of the damaged area. While this technique is effective in regenerating bone, bacterial infiltration occurs frequently and can compromise the regenerative outcome. In this study, the authors describe the development and characterization of a GBR membrane made of medical grade polycaprolactone (mPCL) electrospun fibers with antibacterial and immunomodulatory properties. This is achieved by the immobilization of the antibiotic azithromycin into the membrane via a solvent evaporation technique leading to a sustained release of the drug over 14 d. In vitro testing shows that this controlled release of azithromycin is proficient at inhibiting the growth of Staphylococcus aureus for 14 d. Implantation of azithromycin loaded mPCL membrane in a rodent calvarial defect induces macrophage polarization toward the M2 phenotype after one week and...
Annals of biomedical engineering, Jan 29, 2016
Periodontitis is defined as a chronic inflammatory condition, characterized by destruction of the... more Periodontitis is defined as a chronic inflammatory condition, characterized by destruction of the periodontium, composed of hard (i.e. alveolar bone and cementum) and soft tissues (i.e. gingiva and periodontal ligament) surrounding and supporting the teeth. In severe cases, reduced periodontal support can lead to tooth loss, which requires tissue augmentation or procedures that initiate a repair, yet ideally a regenerative response. However, mimicking the three-dimensional complexity and functional integration of the different tissue components via scaffold- and/or matrix-based guided tissue engineering represents a great challenge. Additive biomanufacturing, a manufacturing method in which objects are designed and fabricated in a layer-by-layer manner, has allowed a paradigm shift in the current manufacturing of medical devices and implants. This shift from design-to-manufacture to manufacture-to-design, seen from a translational research point of view, provides the biomedical engi...
Annals of Physical and Rehabilitation Medicine, 2014
Nous avons mené une étude descriptive rétrospective sur les patients de plus de 18 ans ayant subi... more Nous avons mené une étude descriptive rétrospective sur les patients de plus de 18 ans ayant subi une lésion médullaire traumatique de niveau cervical en Haute Normandie, entre 2002 et 2012. Cent huit patients ont été inclus (49,0 ± 21,1 ans), avec une augmentation de la proportion des chutes. Le ratio homme/femme est de 3,9 hommes pour 1 femme, avec comme niveau le plus fréquemment retrouvé le niveau C5, puis le niveau C6, le niveau C4, le niveau C7, le niveau C8 et le niveau C3. 27,8 % des patients étaient passé en unité de sevrage respiratoire, et 40,7 % avaient une trachéotomie, dont 56,8 % ont pu être sevré de leur trachéotomie. Un pourcentage de 6,5 % nécessitait une assistance ventilatoire mécanique permanente. L'incidence des admissions en secteur de réanimation d'une tétraplégie post-traumatique a été calculée à 12,7 et 13,4 cas par million d'habitants en Haute-Normandie, stable pour les années 2009, 2010, 2011 et 2012. Cette étude montre que la prise en compte de la tétraplégie ventilée reste difficile, et que la création d'une filière de santé nationale dédiée permettrait de servir de recours aux patients et aux équipes les prenant en charge à travers tout le territoire.
Proceedings of the 5th International Conference on Advanced Research in Virtual and Rapid Prototyping, Leiria, Portugal, 28 September - 1 October, 2011, 2011
Polycaprolactone-based scaffold plus BMP-2 in a sheep thoracic spine fusion model.
Advanced healthcare materials, Jan 26, 2015
The ability to test large arrays of cell and biomaterial combinations in 3D environments is still... more The ability to test large arrays of cell and biomaterial combinations in 3D environments is still rather limited in the context of tissue engineering and regenerative medicine. This limitation can be generally addressed by employing highly automated and reproducible methodologies. This study reports on the development of a highly versatile and upscalable method based on additive manufacturing for the fabrication of arrays of scaffolds, which are enclosed into individualized perfusion chambers. Devices containing eight scaffolds and their corresponding bioreactor chambers are simultaneously fabricated utilizing a dual extrusion additive manufacturing system. To demonstrate the versatility of the concept, the scaffolds, while enclosed into the device, are subsequently surface-coated with a biomimetic calcium phosphate layer by perfusion with simulated body fluid solution. 96 scaffolds are simultaneously seeded and cultured with human osteoblasts under highly controlled bidirectional p...
Uploads
Papers by Cedryck Vaquette