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Microbeads consisting of pullulan and dextran supplemented with hydroxyapatite have recently been developed for bone tissue engineering applications. Here, we evaluate the bone formation in two different preclinical models after injection of microbeads reconstituted with either saline buffer or autologous blood. Addition of saline solution or autologous blood to dried microbeads packaged into syringes allowed an easy injection. In the first rat bone defect model performed in the femoral condyle, microcomputed tomography performed after 30 and 60 days revealed an important mineralization process occurring around and within the core of the microbeads in both conditions. Bone volume/total volume measurements revealed no significant differences between the saline solution and the autologous blood groups. Histologically, osteoid tissue was evidenced around and in contact of the microbeads in both conditions. Using the sinus lift model performed in sheep, cone beam computed tomography revealed an important mineralization inside the sinus cavity for both groups after 3 months of implantation. Representative Masson trichrome staining images showed that bone formation occurs at the periphery and inside the microbeads in both conditions. Quantitative evaluation of the new bone formation displayed no significant differences between groups. In conclusion, reconstitution of microbeads with autologous blood did not enhance the regenerative capacity of these microbeads compared to the saline buffer group. This study is of particular interest for clinical applications in oral and maxillofacial surgery.

Purpose The aim of this study was to evaluate and compare bone growth and implant integration in circumferential defects with two commercially available bone substitutes (demineralized bovine bone mineral [DBBM]). Materials and methods Circumferential defects were created in the mandibles of minipigs (n = 10), and Bone Level Tapered implants (Straumann Roxolid with SLActive surface) were placed. The defects (4-mm-deep circumferential defect, 2 mm around each implant) were augmented with either sintered bovine bone mineral (test, cerabone) or natural bovine bone mineral (control, Bio-Oss). Bone formation and tissue composition in augmented sites were histomorphometrically assessed after 8 and 12 weeks of healing time (n = 5 each), respectively, in terms of the percentage of area of newly formed bone to total area, bone-to-implant contact (BIC), and crestal bone height relative to the implant shoulder (first bone-to-implant contact [fBIC]). Results Bone formation in all defect sites was adequate and equivalent for both groups at individual healing time points. The amount of residual graft material was comparable in both groups after 8 and 12 weeks, with no significant resorption in either group. The mean newly formed bone area in the test group amounted to 46.7% ± 5.1% and 48.7% ± 4.0% after 8 and 12 weeks vs 47.0% ± 4.8% and 47.8% ± 7.3% in the control group, respectively. BIC and fBIC as individually assessed for the lingual and buccal aspects were comparable at both healing time points without any statistically significant differences between the groups. A slightly greater variability of fBIC was observed within the test group. Conclusion The results of this study indicate that test and control materials both represent viable bovine bone graft material that equivalently support the formation of new and stable bone volume specifically when used for simultaneous augmentation around implants.

Introduction: The diagnosis of and risks associated with oral potentially malignant disorders (OPMD) have been widely reported, but little has been published on the management of OPMDs in a primary dental care setting. Hospital services face ongoing pressures due to long-term follow-up, with a need for surveillance to be jointly undertaken with primary dental care clinicians. In a primary care setting, identification and surveillance of OPMDs can be challenging as no universal guidance exists on recommended recall intervals. Corpus: In this article, an update on OPMDs is provided and, based on the practices of six Oral Medicine units in Europe (London (United Kingdom), Milan (Italy), Bordeaux (France), Porto (Portugal), Zagreb (Croatia) and Santiago de Compostela (Spain)), aiming to provide guidance on monitoring in a primary care setting in Europe. Conclusion: Oral medicine clinicians can provide guidance to general dental practitioners (GDPs) on recommended recall intervals. It is important that they feel confident in monitoring these conditions and, when concerned, to arrange referral to a hospital or appropriate specialist. GDPs should document descriptions of lesions and, if possible, take clinical photographs. Patients should be counselled on modifiable lifestyle factors and directed to oral medicine society websites to access patient information leaflets.

Introduction The aim of this study was to assess the knowledge and clinical experience of oral potentially malignant disorders (OPMDs) in undergraduate dental students in six European countries (Croatia, France, Italy, Portugal, Spain and United Kingdom) and assess student’s attitude and preference to future education on the topic. A secondary aim was to identify gaps in student’s knowledge and clinical practice. The study was a part of the Erasmus+ project “Oral Potentially Malignant Disorders: Healthcare Professionals Training“ (Grant No: 2020-1-UK01-KA202-078917). Materials and Methods An online questionnaire was distributed to all final-year students in six partner universities. This consisted of four parts assessing: (1) knowledge on OPMDs, (2) clinical experience with this group of patients, (3) self-rated competence in the management of OPMDs and (4) preferences with regard to future education. Results Two hundred and sixty final-year dental students from six partner universities responded to the questionnaire. Response rates varied from 12% to 92% between partner universities. Significant differences in clinical experience and knowledge were found between students. Students with more clinical exposure to OPMDs rated their knowledge and competence in the management of OPMDs higher than students with less clinical experience. The majority of students were interested in future education on OPMDs, preferably via short educational videos. Conclusion The majority of students have received theoretical knowledge of OPMDs during their undergraduate studies, however, not all had clinical exposure to this group of patients. Students were open to further education on OPMDs. Important deficiencies in knowledge were identified that need to be addressed and it is anticipated that the e- learning platform and e-book that are in development by partner institutions will help to improve overall knowledge of OPMDs.

Objective:This study aimed to assess the influence of mandibular third molar surgical removal on the periodontal status of adjacent second molars and to investigate the potential impact of the flap design.Methods:A systematic review of the literature, registered in PROSPERO, has been carried out from Pubmed and Scopus databases following PRISMA guidelines from January 2010 to January 2022. PICO method was used to select the relevant articles. Studies comparing the periodontal status of the second molar before and after mandibular third molar removal were considered.Results:Twenty-three studies involving 1067 patients were included. The two main parameters studied were periodontal pocket depth and clinical attachment level. The envelope flap and the triangular flap were the most commonly used flap techniques. Periodontal health of adjacent second molar was maintained or improved in most of the included studies. The flap design did not seem to have a significant influence either.Conclusion:Avulsion of impacted third molar in healthy young adults does not impair the periodontal health of adjacent second molars. Further studies, with higher levels of evidence, are needed to confirm these results and to identify possible risk factors (such as age, impaction depth or periodontal disease) responsible for poorer healing.

When considering regenerative approaches, the efficient creation of a functional vasculature, that can support the metabolic needs of bioengineered tissues, is essential for their survival after implantation. However, it is widely recognized that the post-implantation microenvironment of the engineered tissues is often hypoxic due to insufficient vascularization, resulting in ischemia injury and necrosis. This is one of the main limitations of current tissue engineering applications aiming at replacing significant tissue volumes. Here, we have explored the use of a new biomaterial, the cell-assembled extracellular matrix (CAM), as a biopaper to biofabricate a vascular system. CAM sheets are a unique, fully biological and fully human material that has already shown stable long-term implantation in humans. We demonstrated, for the first time, the use of this unprocessed human ECM as a microperforated biopaper. Using microvalve dispensing bioprinting, concentrated human endothelial cells (30 millions ml−1) were deposited in a controlled geometry in CAM sheets and cocultured with HSFs. Following multilayer assembly, thick ECM-based constructs fused and supported the survival and maturation of capillary-like structures for up to 26 d of culture. Following 3 weeks of subcutaneous implantation in a mice model, constructs showed limited degradative response and the pre-formed vasculature successfully connected with the host circulatory system to establish active perfusion.This mechanically resilient tissue equivalent has great potential for the creation of more complex implantable tissues, where rapid anastomosis is sine qua non for cell survival and efficient tissue integration.

Implants made of ceramics, and more particularly of calcium phosphates (hydroxyapatite: HA, mainly), promoting intimate contact with natural bone are nowadays merging. Addition of copper ions in bio-ceramics is expected to increase the biological compatibilities of bone graft substitutes. Previous works have shown that copper-doped hydroxyapatite (Cu-doped HA) ceramics can be prepared by solid-state sintering between HA and CuO powder mixtures at about 1100 °C; but, copper-substituted HA was found to be metastable leading to apatitic grains and Cu-rich grain boundaries during the sintering process. Ultra-rapid sintering is so needed. Selective laser sintering (SLS) is an additive manufacturing process that possesses the advantage to be based on ultra-fast sintering process under laser irradiation. SLS being used in literature for the application of laser on polymer-ceramic or poymer-metal composites the proper term all along the paper is Ceramic Powder Bed Laser Sintering (CPBLS). To achieve densification of Cu-doped HA ceramics from CPBLS process, one should control the composition/morphology/structure of the powder bed as well as three other important CPBLS parameters: (i) the applied energy from the laser beam, (ii) the laser power and the laser scanning speed, (iii) the distance between two successive lased lines. In this paper, the impact of all the main CPBLS parameters controlling the sintering of dip-coated Cu-doped HA layers on glass substrates is carefully investigated. Possibility of the creation of thin consolidated Cu-doped HA ceramic patterns, using the ultra-fast CPBLS process, is finally shown.

International audience; Layer-by-layer (LBL) BioAssembly method was developed to enhance the control of cell distribution within 3D scaffolds for tissue engineering applications. The objective of this study was to evaluate in vivo the development of blood vessels within LBL bioassembled membranes seeded with human primary cells, and to compare it to cellularized massive scaffolds. Poly(lactic) acid (PLA) membranes fabricated by fused deposition modeling were seeded with monocultures of human bone marrow stromal cells or with cocultures of these cells and endothelial progenitor cells. Then, four cellularized membranes were assembled in LBL constructs. Early osteoblastic and endothelial cell differentiation markers, alkaline phosphatase, and von Willebrand's factor, were expressed in all layers of assemblies in homogenous manner. The same kind of LBL assemblies as well as cellularized massive scaffolds was implanted subcutaneously in mice. Human cells were observed in all scaffolds seeded with cells, but not in the inner parts of massive scaffolds. There were significantly more blood vessels observed in LBL bioassemblies seeded with cocultures compared to all other samples. LBL bioassembly of PLA membranes seeded with a coculture of human cells is an efficient method to obtain homogenous cell distribution and blood vessel formation within the entire volume of a 3D composite scaffold.

Thanks to its biological properties, the human amniotic membrane (HAM) combined with a bone substitute could be a single-step surgical alternative to the two-step Masquelet induced membrane (IM) technique for regeneration of critical bone defects. However, no study has directly compared these two membranes. We first designed a 3D-printed scaffold using calcium phosphate cement (CPC). We assessed its suitability in vitro to support human bone marrow mesenchymal stromal cells (hBMSCs) attachment and osteodifferentiation. We then performed a rat femoral critical size defect to compare the two-step IM technique with a single-step approach using the HAM. Five conditions were compared. Group 1 was left empty. Group 2 received the CPC scaffold loaded with rh-BMP2 (CPC/BMP2). Group 3 and 4 received the CPC/BMP2 scaffold covered with lyophilized or decellularized/lyophilized HAM. Group 5 underwent a two- step induced membrane procedure with insertion of a polymethylmethacrylate (PMMA) spacer followed by, after 4 weeks, its replacement with the CPC/BMP2 scaffold wrapped in the IM. Micro-CT and histomorphometric analysis were performed after six weeks. Results showed that the CPC scaffold supported the proliferation and osteodifferentiation of hBMSCs in vitro. In vivo, the CPC/BMP2 scaffold very efficiently induced bone formation and led to satisfactory healing of the femoral defect, in a single-step, without autograft or the need for any membrane covering. In this study, there was no difference between the two-step induced membrane procedure and a single step approach. However, the results indicated that none of the tested membranes further enhanced bone healing compared to the CPC/BMP2 group.

The aim of this study was to perform a systematic review on the clinical applications where chorion membrane (CM) and amnion/chorion membrane (ACM) were used for oral tissue regeneration procedures. Selection of articles was carried out by two evaluators in Pubmed and Scopus databases, and Outcomes (PICO) method was used to select the relevant articles. Clinical studies reporting the use of CM or ACM for oral soft and hard tissue regeneration were included. The research involved 21 studies conducted on 375 human patients. Seven clinical applications of CM and ACM in oral and periodontal surgery were identified: gingival recession treatment, intrabony and furcation defect treatment, alveolar ridge preservation, keratinized gum width augmentation around dental implants, maxillary sinus membrane repair, and large bone defect reconstruction. CM and ACM were compared to negative controls (conventional surgeries without membrane) or to the following materials: collagen membranes, dense polytetrafluoroethylene membranes, platelet-rich fibrin membranes, amnion membranes, and to a bone substitute. Several studies support the use of CM and ACM as an efficient alternative to current techniques for periodontal and oral soft tissue regeneration procedures. However, further studies are necessary to increase the level of evidence and especially to demonstrate their role for bone regeneration.

International audience; Additive manufacturing is a rising field in bone tissue engineering. Additive fabrication offers reproducibility, high precision and rapid manufacture of custom patient-specific scaffolds. The development of appropriate composite materials for biomedical applications is critical to reach clinical application of these novel biomaterials. In this work, medical grade poly(lactic-co-glycolic) acid (PLGA) was mixed with hydroxyapatite nanoparticles (nHA) to fabricate 3D porous scaffolds by Fused Deposition Modeling. We have first confirmed that the composite material could be printed in a reproductive manner. Physical characterization demonstrated a low degradation of the material during manufacturing steps and an expected loading and homogeneous distribution of nHA. In vitro biodegradation of the scaffolds showed modifications of morphological and physicochemical properties over time. The composite scaffolds were biocompatible and high cell viability was observed in vitro, as well as a maintain of cell proliferation. As expected, the addition of nHA displayed a positive impact on osteodifferentiation in vitro. Furthermore, a limited inflammatory reaction was observed after subcutaneous implantation of the materials in the rat. Overall, this study suggests that this composite material is suitable for bone tissue engineering applications.

Introduction: White Sponge Nevus (WSN) is a leukokeratosis characterized by white lesions of the oral mucosa. These lesions are bilateral, thickened and raised compared to the adjacent mucosa. Their aspect are folded and spongy. It is a benign disorder with asymptomatics lesions which often appear during the childhood or the adolescence. The interest of this case report is that the diagnostic of WSN had been established directly, thanks to the presence of the patient's father. Observation: A twelve years old patient was examined in the unity of the oral mucosa pathology and oro-facials pain, of the oral surgery service of Bordeaux hospital (CHU de Bordeaux, France). He presented typical WSN lesions. His father was examined and presented the same lesions. Discussion: Diagnostic of WSN is mainly a clinical examination. There are a lot of differential diagnosis, and leukoplakia is the principal. In case of doubt about the diagnostic, a histological examination can be done. Nowadays, there is no consensus about the therapeutic. But the lesions are mainly asymptomatics, so any treatment has to be planed. Conclusion: An early WSN diagnosis avoids to patients a non adapted treatment and reassures young patients and their parents.

International audience; An important component of tissue engineering (TE) is the supporting matrix upon which cells and tissues grow, also known as the scaffold. Scaffolds must easily integrate with host tissue and provide an excellent environment for cell growth and differentiation. Human amniotic membrane (hAM) is considered as a surgical waste without ethical issue, so it is a highly abundant, cost-effective, and readily available biomaterial. It has biocompatibility, low immunogenicity, adequate mechanical properties (permeability, stability, elasticity, flexibility, resorbability), and good cell adhesion. It exerts anti-inflammatory, antifibrotic, and antimutagenic properties and pain-relieving effects. It is also a source of growth factors, cytokines, and hAM cells with stem cell properties. This important source for scaffolding material has been widely studied and used in various areas of tissue repair: corneal repair, chronic wound treatment, genital reconstruction, tendon repair, microvascular reconstruction, nerve repair, and intraoral reconstruction. Depending on the targeted application, hAM has been used as a simple scaffold or seeded with various types of cells that are able to grow and differentiate. Thus, this natural biomaterial offers a wide range of applications in TE applications. Here, we review hAM properties as a biocompatible and degradable scaffold. Its use strategies (i.e., alone or combined with cells, cell seeding) and its degradation rate are also presented.

International audience; Additive manufacturing (AM), especially powder bed laser sintering (PBLS), has been an increasingly popular field since the 1980s. Direct SLS is particularly challenging with ceramic materials due to their low thermal conductivity, high melting point, and brittle mechanical behaviour. In addition, they require longer processing times for a reliable sintering degree. In this work, the impact of some crucial parameters in SLS applied to a copper-doped hydroxyapatite bioceramic was studied. Incorporating copper ions into the hydroxyapatite matrix by thermal treatment can stimulate blood vessel formation, simultaneously improving the material's mechanical integrity and antibacterial properties. Moreover, it facilitates laser power absorption by the material at the laser wavelength. Thin films were prepared with controlled thicknesses using dip-coating on glass substrates, and they were irradiated by an ytterbium laser (1.070 µm wavelength). Experimental laser irradiation was systematically compared to numerical models to predict the maximum temperature produced on the film surface by laser irradiation. The evaluated parameters are the absorptivity from the copper concentration, the film thickness, and the laser source (scanning velocity and power). Combining low laser scanning speeds with low film thickness and optimised absorption tuned by the copper concentration has made possible the development of well-sintered ceramics by the PBLS technique.

Introduction:Frenectomy is an oral surgical procedure usually performed with a scalpel. Several authors recently reported the interest of laser, as a minimally invasive and efficient alternative tool to perform frenectomy. This study aimed to compare the perioperative management of patients requiring a frenectomy using scalpelversuslaser.Materials and methods:A systematic review of the literature has been carried out from Pubmed and Scopus databases following PRISMA guidelines. PICO method was used to select the relevant articles. Clinical studies comparing the perioperative outcomes of patients requiring frenectomies using scalpelversuslaser were included.Results:Ten articles involving 375 patients were included. Pre-operative parameter (anxiety before surgery) and per-operative data such as anesthesia, surgery duration, bleeding, suture and difficulty were assessed. The post-operative outcomes investigated were pain, analgesics use, functional discomfort, edema, healing and satisfaction of patients. Laser achieved satisfactory peri-operative outcomes such as shorter operative time, without suturing requirement, as well as less post-operative pain and functional discomfort.Discussion:The low number of eligible studies, the different type of lasers used and heterogeneity across the methodology of the selected studies were the limits of the study.Conclusion:Laser-assisted surgery became an attractive tool to perform oral soft tissue surgery.

International audience; Background: Bisphosphonates (BPs) are widely used for the prevention or treatment of osteoporosis. One of the most serious complications associated with BPs is medication-related osteonecrosis of the jaw (MRONJ) but its incidence in patients with osteoporosis is very low ranging from 0.001-0.15%. A major predisposing factor for MRONJ is tooth extraction (TE). Controversies persist about the influence of current BP therapy regarding socket healing after TE. The aims of this study were to investigate prospectively, (i) alveolar bone healing, i.e., filling of the bony socket by new bone and (ii) mucosal healing, i.e., closure of the overlying mucosa, after TE in women receiving current BP therapy for the prevention or the treatment of postmenopausal osteoporosis. Methods: Women with osteoporosis under current treatment with BPs (BP+ group) or other anti-osteoporotic medications (BP-group) undergoing single TE were included in this study. No antibiotic prophylaxis was prescribed solely for the BP therapy, but antibiotic treatment may have been required for local infectious conditions. Chlorohexidine mouthwashes were systematically prescribed in all study patients for one week after TE. New bone height (NBH) and rate of socket filling (RSF) were recorded using intraoral standardized radiographs one month and 3 months after TE (T30 and T90 respectively). The closure of the overlying mucosa was assessed by measuring the wound extent with an electronic caliper at 1 week and at 1 month after TE (T7 and T30 respectively). Results: At T30, NBH was not statistically different between the BP+ and BP-groups (p = .76). At T90, more than a twofold in NBH increase was recorded for both groups with no statistically significant difference between them (p = .76). At T30 and T90, RSF was similar in both groups (p = .58 and p = .32 respectively). More than a twofold RSF increase was founded between T30 and T90 in both groups. No demographic or BPs-related factors were correlated with the RSF at T90. At T7, the mucosa wound extent was reduced by more than twofold with no statistically significant difference between both groups (p = .80). At this time, mucosa healing was achieved in 11.9% of the BP+ group and 10% of the BP-group (p = .99). At T30, mucosal healing was achieved in all patients but two, and at T90 it was achieved in all patients. Conclusion: This study provides new insights into bone and mucosal healing in patients with osteoporosis taking BPs after TE. In this population, TE can be managed successfully with an appropriate surgical protocol and without discontinuation of BP treatment.

3D organization of cells and biomaterials (scaffolds) for tissue engineering enhances cell-to-cell communication through growth factor secretion and extracellular matrix formation. The main limitation of tissue engineering is the low penetration of cells in inner parts of large engineered products, due to the insufficient diffusion of oxygen and nutrients. The layer-by-layer bioassembly approach consists of combinations of different smaller scaffolds in the form of porous membranes seeded with cells in order to obtain final tissue engineering constructs with controlled 3D organization. Membranes for tissue engineering can be of natural (animal or human) and synthetic (biopolymers) origin. Disadvantages of human origin membranes are the possibility of immune response or pathogenic transmission, and lack of availability, which are overcome in the case of synthetic biopolymers. There is a wide range of possibilities in combinations of membranes seeded with cells to fabricate final complex tissue engineered products with controlled 3D microarchitecture and microenvironment.

International audience; Hydroxyapatite coatings have been currently used on hip prostheses for their ability to promote faster osseointe- gration and bone growth. Nevertheless, post-operative infections remain a recurring problem. To overcome this issue, doping with antibacterial elements has become a new trend. In this work, hydroxyapatite coatings elab- orated by radio-frequency suspension plasma spraying (rf-SPS) were doped with silver and strontium. Several doping strategies were explored thanks to the versatility offered by SPS compared with conventional spraying. First way: calcium phosphate doped powders were synthesized by coprecipitation and then dispersed into water before plasma spraying; second way: undoped powder was dispersed into aqueous medium in which nitrates or nanoparticles of the dopant(s) were respectively dissolved/dispersed. XRD revealed a high level of crystallinity ratio (ISO 13 779) and hydroxyapatite proportion for most of the coatings, with the presence of Ag/Ag 2 O nanopar- ticles whatever the doping route. SEM-EDS and STEM have demonstrated a more homogeneous distribution of the strontium within the coating made from the doped powder. Adherence of the coatings was estimated via a 3-point bending test, while bacteriological tests with S. aureus and proliferation of mesenchymal stem cells (hMSC) were performed. The results indicated a preferential incorporation of strontium into the secondary phases, showed efficient bactericidal properties, excellent mechanical properties in comparison with an APS reference coating, and no evidence of cytotoxic effect. This opens the way of a new type of coatings with a finer structure and a higher homogeneity through a better control of physicochemical properties using a suspension as the precursor.

Introduction: Direct tissue autofluorescence (AF) visualization devices such as VELscope® are gaining interest to improve early detection of oral potentially malignant disorders (OPMD) and cancers. The main objective of this study was to assess inter-observer reproducibility of incandescent light (IL) and AF observations for OPMD and cancer. Materials and methods: High risk patients (exposed to alcohol or tobacco) were screened by two independent operators with a conventional oral examination (IL) followed by AF examination. The primary endpoint was the inter-observer agreement on the decision to biopsy assessed by kappa coefficients.Accuracy of IL and AF were estimated by the relative true positive rate (RTPR, increase of sensitivity), relative false positive rate (RFPR, loss of specificity) and their ratio. Results: 179 patients were included. 833 lesions were identified after IL and AF. Indication for biopsy was retrieved for 41 patients (61 lesions). Inter-observer agreement on the indications for biopsy was 93.3% after IL (Kappa coefficient 0.88 [0.80, 0.97]) and 96.1% after IL and AF (Kappa coefficient 0.78 [0.66, 0.90]). RTPR was 1.2, RFPR was 1 and their ratio was 1.2. Conclusion: IL and AF examination has shown good inter-observer reproducibility. Adjunction of AF allowed diagnosing more leukoplakia without dysplasia.

Introduction: Post-traumatic painful trigeminal neuropathy is a chronic facial pain secondary to trigeminal nerve injury. The treatment of this pain is a therapeutic issue due to the alteration of quality of life that it generates. Observation: A 58-year-old man whose main history of facial trauma has been consulted in the Odontology Department for bilateral trigeminal neuropathic pain that has been evolving for several months. The interrogation revealed continuous pain like electric shocks in the canine areas and daily painful exacerbations. Hyperesthesia and allodynia were found on clinical examination. The patient had received several treatments, oral and local, without significant improvement. As a last resort, injections of ropivacaine every 2 weeks associated with pregabalin (200 mg/day) were performed. At 6 months, there was a clear decrease in the burning sensation and a complete disappearance of painful exacerbations. Discussion: Two studies have recently shown the benefit of the combination of an antiepileptic and a local analgesic in the treatment of classical trigeminal neuralgia, justifying their use in a context of post-traumatic neuropathic pain. Conclusion: Further studies with higher levels of evidence are needed to confirm these preliminary results.

International audience; Objective: Polysaccharide-based composite matrices consisting of natural polysaccharides, pullulan and dextran supplemented with hydroxyapatite (Matrix-HA) have recently been developed. The principal objective of this study was to evaluate the capacities of this composite material to promote new bone formation in a sinus lift model in the sheep. Secondary objectives were to evaluate in vitro properties of the material regarding cell adhesion and proliferation.Methods: In this report, once such composite matrix was prepared as injectable beads after dispersion in a physiological buffer, and evaluated using a large animal model (sheep) for a sinus lift procedure.Results: In vitro studies revealed that these microbeads (250-550μm in diameter) allow vascular cell adhesion and proliferation of Endothelial Cells (EC) after 1 and 7 days of culture. In vivo studies were performed in 12 adult sheep, and newly formed tissue was analyzed by Cone Beam Computed Tomography (CBCT scanning electron microscopy (SEM) and by histology 3 and 6 months post-implantation. CBCT analyses at the implantation time revealed the radiolucent properties of these matrices. Quantitative analysis showed an increase of a dense mineralized tissue in the Matrix-HA group up to 3 months of implantation. The mineralized volume over total volume after 6 months reached comparable values to those obtained for Bio-Oss® used as positive control. Histological examination confirmed that the Matrix-HA did not induce any long term inflammatory events, and promoted direct contact between the osteoid tissue and lamellar bone structures and beads. After 6 months, we observed a dense network of osteocytes surrounding both biomaterials as well as a newly vascularized formed tissue in close contact to the biomaterials.Significance: In conclusion, the absence of animal components in Matrix-HA, the osteoconductive property of Matrix-HA in sheep, resulting in a dense bone and vascularized tissue, and the initial radiolucent property to follow graft integration offer great promises of this composite material for clinical use.

Abstract: By utilizing the ‘stages of change’ approach to smoking cessation an individual's willingness to quit smoking can be ascertained, with provision of knowledge on potential interventions empowering patients to make their own decisions on cessation modalities. Nicotine Replacement Therapy (NRT) can reduce physical cravings, pharmacotherapies can reduce the desire to smoke, stop smoking services can provide smokers with interpersonal support and electronic cigarettes are increasing in popularity but cannot be recommended as a completely safe way of delivering nicotine. Interpersonal support in combination with NRT and/or pharmacotherapy is the safest and most successful method of smoking cessation. The authors are developing an online resource to assist with smoking cessation advice. It is available at http://www.smokingcessationtraining.com/ . CPD/Clinical Relevance: For a patient who is amenable to brief cessation advice, the stages of change model allows the dentist to adapt brief advice to the patient's current circumstances. By improving knowledge of smoking cessation modalities, the dentist can answer any simple questions the patient may have, signposting them towards specialist cessation centres when appropriate.

Abstract: In Europe, 29% of individuals identify as smokers, with tobacco use directly related to 650,000 mortalities each year across the continent; roughly 14% of all deaths. From a dental perspective, smoking is directly implicated in numerous chronic, and potentially life-threatening, sequelae which exclusively affect the oral cavity. By familiarizing the dental team with gold-standard cessation advice, it can be ensured that smokers are assisted at every available opportunity. Dentists should aim to give cessation advice to smokers based on how willing they are to change their smoking habit. The authors are developing an online resource to assist with smoking cessation advice. It is available at http://www.smokingcessationtraining.com/ CPD/Clinical Relevance: Dentists will see many smokers regularly, and advice should be given routinely to this cohort of patients. By improving understanding of potential oral sequelae and identifying individuals who may wish to quit, targeted advice can be offered to increase cessation success. Brief patient-centred advice ensures the highest chance of delivering successful smoking cessation, alongside safeguarding time for the dentist to examine and treat the individual.

Introduction: Von Willebrand Disease is the most common inherited bleeding disorder. In the general population, 1/8000 patients are affected. Primary hemostasis (platelet adhesion) and coagulation (protection of Factor VIII) are altered. Among several bleeding symptoms, these patients suffer from excessive bleeding of oral mucosa and dental management requires a close collaboration between haematologists and oral surgeons. Materials & Methods: Guided implant surgery can be used to increase the accuracy of implant placement and to reduce the overall morbidity of this surgical procedure by using a flapless surgery technique. Case Report: We report the case of a 49 years old woman having a Type 2A von Willebrand disease and who presented to replace tooth #.46 because of interradicular fracture and peri-apical infection. After planning the implant surgery using Codiagnostix® software, a surgical guide was prepared. The patient received 4 injections of von Willebrand factor (Willfactin®) for this particular surgical procedure. The implant was placed immediately after tooth removal and local haemostasis was performed. Discussion: The follow-up was uneventful and the implant was restored by a crown 4 months later. Two cases of implant placement in haemophiliac patients have been reported before in the literature. Conclusion: As far as we know, this is the first case report of implant placement in a patient having a von Willebrand disease. The use of guided surgery allowed to perform a mini-invasive procedure and thus contributed to prevent bleeding complications in this patient.

Autografts remain the gold standard for orthopedic transplantations. However, to overcome its limitations, bone tissue engineering proposes new strategies. This includes the development of new biomaterials such as synthetic polymers, to serve as scaffold for tissue production. The objective of this present study was to produce poly(lactic) acid (PLA) scaffolds of different pore size using fused deposition modeling (FDM) technique and to evaluate their physicochemical and biological properties. Structural, chemical, mechanical, and biological characterizations were performed. We successfully fabricated scaffolds of three different pore sizes. However, the pore dimensions were slightly smaller than expected. We found that the 3D printing process induced decreases in both, PLA molecular weight and degradation temperatures, but did not change the semicrystalline structure of the polymer. We did not observe any effect of pore size on the mechanical properties of produced scaffolds. After the sterilization by γ irradiation, scaffolds did not exhibit any cytotoxicity towards human bone marrow stromal cells (HBMSC). Finally, after three and seven days of culture, HBMSC showed high viability and homogenous distribution irrespective of pore size. Thus, these results suggest that FDM technology is a fast and reproducible technique that can be used to fabricate tridimensional custom-made scaffolds for tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 887-894, 2018.

Resume Un mauvais etat bucco-dentaire maternel est associe a certaines complications de la grossesse et predispose l’enfant a naitre a l’apparition de caries precoces. Il est donc important que les femmes enceintes ne negligent pas leur hygiene et sante dentaires. Le pharmacien doit sensibiliser ses patientes a cette prise en charge.

International audience; Human amniotic membrane (hAM) is considered as an attractive biological scaffold for tissue engineering. For this application, hAM has been mainly processed using cryopreservation, lyophilization and/or decellularization. However, no study has formally compared the influence of these treatments on hAM properties. The aim of this study was to develop a new decellularization-preservation process of hAM, and to compare it with other conventional treatments (fresh, cryopreserved and lyophilized). The hAM was decellularized (D-hAM) using an enzymatic method followed by a detergent decellularization method, and was then lyophilized and gamma-sterilized. Decellularization was assessed using DNA staining and quantification. D-hAM was compared to fresh (F-hAM), cryopreserved (C-hAM) and lyophilized/gamma-sterilized (L-hAM) hAM. Their cytotoxicity on human bone marrow mesenchymal stem cells (hBMSCs) and their biocompatibility in a rat subcutaneous model were also evaluated. The protocol was effective as judged by the absence of nuclei staining and the residual DNA lower than 50 ng/mg. Histological staining showed a disruption of the D-hAM architecture, and its thickness was 84% lower than fresh hAM (p < 0.001). Despite this, the labeling of type IV and type V collagen, elastin and laminin were preserved on D-hAM. Maximal force before rupture of D-hAM was 92% higher than C-hAM and L-hAM (p < 0.01), and D-hAM was 37% more stretchable than F-hAM (p < 0.05). None of the four hAM were cytotoxic, and D-hAM was the most suitable scaffold for hBMSCs proliferation. Finally, D-hAM was well integrated in vivo. In conclusion, this new hAM decellularization process appears promising for tissue engineering applications.

International audience; Purpose: Only limited information on the effect of implant surface hydrophilicity in conjunction with simultaneous bone augmentation is available. In this study, new bone growth around implants with a superhydrophilic modSLA (SLActive) and hydrophobic SLA (SLA) surface were compared in circumferential defects when grafted in conjunction with mineralized cancellous bone allograft (MCBA, maxgraft) or sintered bovine bone mineral (SBBM, cerabone).Materials and methods: The osseointegration and bone formation in circumferential defects in minipig mandibles around Straumann Roxolid, Ø 3.3 mm, length 8 mm; either SLA or SLActive, were evaluated. Following implant placement, the 2-mm circumferential defects around the implants were filled with MCBA or SBBM. Distance from implant shoulder to first bone-to-implant contact (f-BIC), percentage of bone-to-implant contact (BIC), and bone aggregate percentage (amount of new bone and remaining graft) within the defect area were evaluated after 8 weeks of healing.Results: In the SBBM group, lingual fBIC and buccal BIC were significantly lower for SLA (mean -0.404 ± 0.579 mm for modSLA versus -1.191 ± 0.814 mm for SLA, P = .021 and mean 62.61% ± 9.49% for modSLA versus 34.67% ± 24.41% for SLA, P = .047, respectively). Bone aggregate percentage was significantly higher for modSLA versus SLA implants in SBBM (77.84% ± 6.93% versus 64.49% ± 13.12%; P = .045). The differences between implant surfaces in MCBA showed a similar trend but were less pronounced than in the SBBM group and did not reach a statistically significant level.Conclusion: The results suggest that implants with a superhydrophilic modSLA surface are more conducive to faster osseointegration even in conjunction with simultaneous bone grafting procedures.

Case report: A 71-year-old patient, with no notable medical-surgical history, was referred for a specialized consultation with Oral Mucosal Pathology for tumefaction on the dorsal side of the tongue. It was a nodular lesion measuring one centimeter long, purplish, and painless. There was nothing found through palpation. Surgical excision with a laser diode was performed under local anesthesia. The postoperative follow-up was simple. The patient was seen 3 months later without any sign of recurrence. Histopathological analysis revealed a vegetative intravascular hemangioendothelioma. Comments: This case is rare because of the location of the tumor, and moreover because the subject is male. A laser diode was chosen to resect the lesion because of the purple color which could have resulted in a possible vascular lesion. Indeed, the limits of excision were coagulated, which facilitated the surgery time and any limited postoperative hemorrhagic complications that could have occurred.

Introduction: Cystic maxillary lesions are common. In 1962, Gorlin described a rare cystic form termed the calcifying odontogenic cyst (COC) or Gorlin's cyst. Two cases of this form were treated at Bordeaux University Hospital. Observation: The first case was a 17-year-old patient with mandibular odontoma, which had developed over the previous 6 months. Excision was performed under local anesthesia, and the diagnosis of COC was made following pathological analysis. A 6-month follow-up was planned. The second case was a 62-year-old patient with a post-extraction mandibular lesion, which had been evolving for 1 year. Enucleation under local anesthesia led to the diagnosis of COC. No recurrence was observed after 5 years of follow-up. Discussion: COCs are rare lesions affecting mainly the anterior aspect of the mandible. COCs are usually discovered in unforeseen circumstances, and they can be observed as a clinically painless and well-defined oral deformation. Radiological examination often reveals radiolucent and uniloculated lesions, sometimes associated with radiopaque lesions. Pathological analyses are required for final diagnosis. Management is based on complete excision, more or less associated with marsupialization, and requires an annual clinical radiographic monitoring over the next 5 years. Conclusion: COC are rare lesions, usually asymptomatic, whose treatment is based on complete excision. Clinical and radiological follow-up is necessary until complete reossification is achieved.

International audience; Development of a microvasculature into tissue-engineered bone substitutes represents a current challenge. Seeding of endothelial cells in an appropriate environment can give rise to a capillary-like network to enhance prevascularization of bone substitutes. Advances in biofabrication techniques, such as bioprinting, could allow to precisely define a pattern of endothelial cells onto a biomaterial suitable for in vivo applications. The aim of this study was to produce a microvascular network following a defined pattern and preserve it while preparing the surface to print another layer of endothelial cells. We first optimise the bioink cell concentration and laser printing parameters and then develop a method to allow endothelial cells to survive between two collagen layers. Laser-assisted bioprinting (LAB) was used to pattern lines of tdTomato-labeled endothelial cells cocultured with mesenchymal stem cells seeded onto a collagen hydrogel. Formation of capillary-like structures was dependent on a sufficient local density of endothelial cells. Overlay of the pattern with collagen I hydrogel containing vascular endothelial growth factor (VEGF) allowed capillary-like structures formation and preservation of the printed pattern over time. Results indicate that laser-assisted bioprinting is a valuable technique to pre-organize endothelial cells into high cell density pattern in order to create a vascular network with defined architecture in tissue-engineered constructs based on collagen hydrogel.

International audience; Applications in additive manufacturing technologies for bone tissue engineering applications requires the development of new biomaterials formulations. Different three-dimensional (3D) printing technologies can be used and polymers are commonly employed to fabricate 3D printed bone scaffolds. However, these materials used alone do not possess an effective osteopromotive potential for bone regeneration. A growing number of studies report the combination of polymers with minerals in order to improve their bioactivity. This review exposes the state-of-the-art of existing 3D printed composite biomaterials combining polymers and minerals for bone tissue engineering. Characterization techniques to assess scaffold properties are also discussed. Several parameters must be considered to fabricate a 3D printed material for bone repair (3D printing method, type of polymer/mineral combination and ratio) because all of them affect final properties of the material. Each polymer and mineral has its own advantages and drawbacks and numerous composites are described in the literature. Each component of these composite materials brings specific properties and their combination can improve the biological integration of the 3D printed scaffold. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2579-2595, 2019.

Introduction : Le myelome multiple est une pathologie caracterisee par une proliferation plasmocytaire maligne intramedullaire. Il se manifeste par la synthese massive d’une paraproteine monoclonale immunoglobulinique. Lorsqu’il s’agit d’un fragment de chaine legere, il peut se compliquer d’une amylose AL systemique. Les depots amyloides au niveau de la langue peuvent alors etre a l’origine de macroglossies plus ou moins invalidantes. L’atteinte linguale a peu ete decrite dans la litterature. Un nouveau cas severe d’amylose AL linguale est rapporte. Observation : Un patient de 62 ans etait adresse pour une gene linguale importante associee a des douleurs. Il etait atteint d’un myelome multiple depuis 2006, traite initialement par melphalan et autogreffe, puis par plusieurs lignes de chimiotherapie en fonction des episodes evolutifs. Une amylose AL avait ete evoquee en 2014 suite a la survenue d’un syndrome du canal carpien bilateral. Lors de son traitement chirurgical, une biopsie synoviale avait revele la presence de depots amyloides. A l’examen clinique, on retrouvait une macroglossie avec indentations laterales. La langue etait ankylosee, induree et douloureuse a la palpation. Le patient rapportait une grande difficulte a s’alimenter (dysphagie, odynophagie, incapacite a deglutir les aliments solides) a l’origine d’une alteration de l’etat general avec amaigrissement. La phonation etait alteree et l’hygiene orale compromise. La biopsie et l’examen anatomopathologique confirmerent la localisation linguale de lesion d’amylose. Un ajustement occlusal au niveau des dents cuspidees ainsi qu’une infiltration locale de triamcinolone furent realises, mais aucune amelioration clinique ne fut obtenue. Discussion : L’amylose est une pathologie definie par le depot et l’accumulation extracellulaire d’une substance proteique dite « amyloide ». Elle peut toucher un ou plusieurs organes, dont elle perturbe l’architecture et la fonction. L’amylose AL (amylose « primitive ») est typiquement secondaire a une proliferation plasmocytaire comme dans le myelome multiple. Dans celle-ci, les fibrilles de la substance amyloide sont constituees par la polymerisation de fragments monoclonaux de chaines legeres d’immunoglobulines. Les manifestations orales sont parfois les premiers signes de la maladie. Le principe du traitement est de reduire la charge proteique en agissant sur la proliferation monoclonale sous-jacente. Le pronostic depend de la reduction de la concentration serique en chaines legeres libres. En raison d’un manque de donnees et de l’absence de preuve scientifique, il n’existe pas de consensus sur la gestion specifique de la macroglossie due a une amylose systemique. Le traitement chirurgical par glossectomie partielle peut etre envisage en cas d’impotence fonctionnelle ou esthetique majeure, dans la mesure ou la proliferation monoclonale sous-jacente est supprimee. Dans le cas present, l’importance de la gene fonctionnelle consecutive a la macroglossie necessitait une prise en charge symptomatique. Le risque de recidive, l’impredictibilite du resultat postoperatoire et l’importante morbidite inherente a la glossectomie ont contre-indique ce traitement en premiere intention. Pour les cas evolutifs d’amylose systemique avec blocage pharynge, des mesures alternatives comme la tracheotomie et la gastrostomie peuvent etre les meilleures solutions pour permettre une qualite de vie acceptable. Conclusion : L’amylose AL est une pathologie multisystemique de pronostic sombre, dont l’esperance de vie sans traitement est inferieure a 1 an. En presence de cas evolutifs, le maintien de la qualite de vie du patient et la protection des fonctions vitales sont essentiels.

Introduction : La cicatrisation alveolaire post-extractionnelle est accompagnee systematiquement d'une resorption osseuse plus ou moins importante selon les sites anatomiques et la pathologie initiale. Cette resorption osseuse peut parfois compromettre la mise en place d'implants dentaires. L’objectif de cette revue systematique de la litterature etait d'evaluer si les eponges de collagene permettaient de limiter cette resorption osseuse. Materiels et methodes : Les bases de donnees Medline et Pubmed ont ete consultees pour la periode 1986-2015. Resultats : Les etudes comparant les eponges de collagene a une cicatrisation naturelle n'ont pas montre de difference significative en ce qui concerne la cicatrisation alveolaire. En revanche, les etudes comparant l'implantation d'une eponge de collagene comme vecteur de facteurs de croissance a une eponge de collagene seule montraient un effet positif des facteurs de croissance pour corriger un defaut osseux parodontal ou pour limiter la resorption post-extractionnelle. Discussion : Il n’y a pas d’interet a placer une eponge de collagene seule dans une alveole d’extraction pour limiter la resorption osseuse. En revanche, la mise en place dans l’alveole d’une eponge de collagene associee a des facteurs de croissance permet de maintenir la hauteur et la largeur de la crete alveolaire. Conclusion : Les eponges de collagene doivent etre utilisees uniquement comme des hemostatiques locaux apres une extraction dentaire. Rien n’indique dans la litterature que ces eponges pourraient avoir un role dans le maintien du volume osseux alveolaire.

Introduction : Le syndrome APECED (Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy) est une maladie autosomique recessive caracterisee par l’association d’une atteinte endocrinienne auto-immune, d’une candidose cutaneo-muqueuse et d’une atteinte des tissus ectodermiques. Observation : Le cas d’un patient de 19 ans atteint d’un syndrome APECED est rapporte. Les signes retrouves etaient une maladie d’Addison, une keratopathie et une alopecie. Le diagnostic de candidose cutaneo-muqueuse a ete plusieurs fois porte mais jamais formellement prouve chez ce patient. Un lichen plan atrophique a ete diagnostique cliniquement et histologiquement sur la muqueuse buccale. Il a ete traite par clobetasol topique. Discussion : L’apparition d’un lichen plan est inhabituelle dans ce syndrome. La question du caractere fortuit ou non du lichen et de la confusion diagnostique avec une candidose est posee. Conclusion : Les praticiens specialistes de la cavite orale devraient connaitre cette dystrophie muqueuse car elle peut etre associee a des manifestations orales plus communes comme le lichen plan ou la candidose orale.

Observation: An 82-year-old patient treated with the antihistamine ebastine (Kestin ® ) for allergic rhinitis presented for gingival pain. The diagnosis of mucous membrane pemphigoid was suspected after a positive pinch test. Blood examinations highlighted AC anti-PBGA2, and the gingival biopsy showed an epithelioconjunctival delamination and the presence of anti-IgA antibody and C3 deposition along the basal of the membrane. Topical corticosteroid administration was initiated. The symptoms improved but elevated IgA and C3 levels persisted. He underwent a complete remission on cessation of ebastine treatment. Commentary: Mucous membrane pemphigoid is an autoimmune disease whose origin remains unclear. The aim of the treatment is to decrease the symptoms, but full recovery of the patients is exceptional. We report here a clinical case with symptom resolution because of the ebastine withdrawal. Ebastine can thus be suspected as a cause if a patient presents with oral symptoms of mucous membrane pemphigoid.

Introduction: Pterygoid hamulus syndrome (PHS) is a little-known differential diagnosis of orofacial pain. It is characterized by oropharyngeal pain, secondary to inflammatory bursitis of the tensor veli muscle of post-traumatic origin, frequently fostered by an associated hypertrophy of the hamular process. Observation: A 64-year-old female patient, type 2 diabetic, consulted for constant posterior palatal pain located near to 17, lasting for 10 years. The inspection did not reveal any mucosal lesions. Right hamulus palpation increased the pain and revealed hamulus hypertrophy. A diagnosis of PHS was evoked. Comment: A review of the literature is proposed. The treatment of PHS is initially conservative, but a surgical treatment can be proposed in case of morphological anomalies. Conclusion: PHS is a little-known syndrome whose diagnosis must be mentioned by the oral surgeon faced with chronic oropharyngeal pain. The diagnosis is clinical and radiological, the treatment is medical and/or surgical.

Introduction : Le syndrome d’Ascher (SA) a ete decrit pour la premiere fois en 1920 par Ascher. Le SA est caracterise par l’association d’une tumefaction du versant muqueux de la levre superieure realisant une double levre, un blepharochalasis bilateral et un goitre thyroidien non toxique (non indispensable au diagnostic). Observation : Un patient de 30 ans sans antecedent medico-chirurgical consultait pour une double levre responsable d’un desagrement esthetique. L’interrogatoire revelait l’apparition de la double levre a l’adolescence. L’examen clinique confirmait la double levre et mettait en evidence un prolapsus des paupieres superieures avec un ptosis plus accentue a droite. Une exerese au laser diode de la double levre etait realisee sous anesthesie locale. Discussion : Des cas de double levres ne rentrant pas dans le cadre d’un SA ont ete decrits. La levre superieure est le plus souvent atteinte mais des cas touchant la levre inferieure ou les deux levres ont ete decrits. Les doubles levres seraient dues a une hypertrophie du chorion sans participation du muscle orbiculaire. La majorite des auteurs realisent une incision elliptique associee a une plastie en Z ou W pour traiter ces lesions. L’utilisation du laser diode presente plusieurs avantages : hemostase, absence de suture, rapidite et simplicite du geste et diminution des suites operatoires.

Introduction : La pycnodysostose est une maladie osseuse autosomique recessive, dont la prevalence est de 1/1,7 million. Elle se caracterise cliniquement par un nanisme, une osteosclerose diffuse, une acro-osteolyse des phalanges distales et une fragilite osseuse avec des fractures. La pycnodysostose presente des specificites maxillo-faciales : une hypoplasie maxillaire et mandibulaire ainsi que des retards d’eruption dentaire. Observations : Les observations de deux patients atteints de pycnodysostose qui presentaient des complications maxillo-faciales caracteristiques de cette maladie sont rapportees et discutees. Les deux patients ont beneficie d’une prise en charge en milieu hospitalier. Le premier patient souffrait d’une osteomyelite maxillaire et mandibulaire. Le deuxieme patient presentait des fractures mandibulaires pathologiques. Discussion : Ces observations sont ensuite comparees a celles retrouvees dans la litterature. La pycnodysostose est une maladie osseuse sclerosante due a une mutation du gene de la cathepsine K. La consequence est une fragilite osseuse associee a de nombreuses fractures et osteites identiques a celles des deux observations rapportees. Conclusion : Le patient atteint de pycnodysostose doit faire l’objet de soins dentaires reguliers pour eviter les complications osseuses et les avulsions dentaires, d’autant que la rehabilitation est compliquee par la morphologie des maxillaires et la structure osseuse.

Current approaches in bone tissue engineering have shown limited success, mostly owing to insufficient vascularization of the construct. A common approach consists of co-culture of endothelial cells and osteoblastic cells. This strategy uses cells from different sources and differentiation states, thus increasing the complexity upstream of a clinical application. The source of reparative cells is paramount for the success of bone tissue engineering applications. In this context, stem cells obtained from human bone marrow hold much promise. Here, we analyzed the potential of human whole bone marrow cells directly expanded in a three-dimensional (3D) polymer matrix and focused on the further characterization of this heterogeneous population and on their ability to promote angiogenesis and osteogenesis, both in vitro and in vivo, in a subcutaneous model. Cellular aggregates were formed within 24 h and over the 12-day culture period expressed endothelial and bone-specific markers and a specific junctional protein. Ectopic implantation of the tissue-engineered constructs revealed osteoid tissue and vessel formation both at the periphery and within the implant. This work sheds light on the potential clinical use of human whole bone marrow for bone regeneration strategies, focusing on a simplified approach to develop a direct 3D culture without two-dimensional isolation or expansion.