The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone) seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step) or only after six weeks of subcutaneous “incubation” (2-step). After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

Engineered and devitalized hypertrophic cartilage (HC) has been proposed as bone substitute material, potentially combining the features of osteoinductivity, resistance to hypoxia, capacity to attract blood vessels, and customization potential for specific indications. However, in comparison with vital tissues, devitalized HC grafts have reduced efficiency of bone formation and longer remodeling times. We tested the hypothesis that freshly harvested stromal vascular fraction (SVF) cells from human adipose tissue—which include mesenchymal, endothelial, and osteoclastic progenitors—enhance devitalized HC remodeling into bone tissue. Human SVF cells isolated from abdominal lipoaspirates were characterized cytofluorimetrically. HC pellets, previously generated by human bone marrow-derived stromal cells and devitalized by freeze/thaw, were embedded in fibrin gel with or without different amounts of SVF cells and implanted either ectopically in nude mice or in 4-mm-diameter calvarial defects in nude rats. In the ectopic model, SVF cells added to devitalized HC directly contributed to endothelial, osteoblastic, and osteoclastic populations. After 12 weeks, the extent of graft vascularization and amount of bone formation increased in a cell-number-dependent fashion (up to, respectively, 2.0-fold and 2.9-fold using 12 million cells per milliliter of gel). Mineralized tissue volume correlated with the number of implanted, SVF-derived endothelial cells (CD31+ CD34+ CD146+). In the calvarial model, SVF activation of HC using 12 million cells per milliliter of gel induced efficient merging among implanted pellets and strongly enhanced (7.3-fold) de novo bone tissue formation within the defects. Our findings outline a bone augmentation strategy based on off-the-shelf devitalized allogeneic HC, intraoperatively activated with autologous SVF cells. Significance: This study validates an innovative bone substitute material based on allogeneic hypertrophic cartilage that is engineered, devitalized, stored, and clinically used, together with autologous cells, intraoperatively derived from a lipoaspirate. The strategy was tested using human cells in an ectopic model and an orthotopic implantation model, in immunocompromised animals.

Background: Bisphosphonate-associated osteonecrosis of the jaws (MRONJ/BP-ONJ/BRONJ) is a commonly seen disease. During recent decades, major advances in diagnostics have occurred. Once the clinical picture shows typical MRONJ features, imaging is necessary to determine the size of the lesion. Exposed bone is not always painful, therefore a thorough clinical examination and radiological imaging are essential when MRONJ is suspected. Methods: In this paper we will present the latest clinical update on the imaging options in regard to MRONJ: X-ray/Panoramic Radiograph, Cone Beam Computed Tomography (CBCT) and Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Nuclear Imaging, Fluorescence-Guided Bone Resection. Conclusion: Which image modality is chosen depends not only on the surgeon’s/practitioner’s preference but also on the available imaging modalities. A three-dimensional imaging modality is desirable, and in severe cases necessary, for extended resections and planning of reconstruction.

Most bones of the human body form and heal through endochondral ossification, whereby hypertrophic cartilage (HyC) is formed and subsequently remodeled into bone. We previously demonstrated that HyC can be engineered from human mesenchymal stromal cells (hMSC), and subsequently devitalized by apoptosis induction. The resulting extracellular matrix (ECM) tissue retained osteoinductive properties, leading to ectopic bone formation. In this study, we aimed at engineering and devitalizing upscaled quantities of HyC ECM within a perfusion bioreactor, followed by in vivo assessment in an orthotopic bone repair model. We hypothesized that the devitalized HyC ECM would outperform a clinical product currently used for bone reconstructive surgery. Human MSC were genetically engineered with a gene cassette enabling apoptosis induction upon addition of an adjuvant. Engineered hMSC were seeded, differentiated, and devitalized within a perfusion bioreactor. The resulting HyC ECM was subsequently implanted in a 10-mm rabbit calvarial defect model, with processed human bone (Maxgraft^®) as control. Human MSC cultured in the perfusion bioreactor generated a homogenous HyC ECM and were efficiently induced towards apoptosis. Following six weeks of in vivo implantation, microcomputed tomography and histological analyses of the defects revealed an increased bone formation in the defects filled with HyC ECM as compared to Maxgraft^®. This work demonstrates the suitability of engineered devitalized HyC ECM as a bone substitute material, with a performance superior to a state-of-the-art commercial graft. Streamlined generation of the devitalized tissue transplant within a perfusion bioreactor is relevant towards standardized and automated manufacturing of a clinical product.

Distraction osteogenesis is a clinically established technique for lengthening, molding and shaping bone by new bone formation. The experimental evaluation of this expensive and time-consuming treatment is of high impact for better understanding of tissue engineering but mainly relies on a limited number of histological slices. These tissue slices contain two-dimensional information comprising only about one percent of the volume of interest. In order to analyze the soft and hard tissues of the entire jaw of a single rat in a multimodal assessment, we combined micro computed tomography (µCT) with histology. The µCT data acquired before and after decalcification were registered to determine the impact of decalcification on local tissue shrinkage. Identification of the location of the H&E-stained specimen within the synchrotron radiation-based µCT data collected after decalcification was achieved via non-rigid slice-to-volume registration. The resulting bi- and tri-variate histograms were divided into clusters related to anatomical features from bone and soft tissues, which allowed for a comparison of the approaches and resulted in the hypothesis that the combination of laboratory-based µCT before decalcification, synchrotron radiation-based µCT after decalcification and histology with hematoxylin-and-eosin staining could be used to discriminate between different types of collagen, key components of new bone formation.

This study aimed to evaluate the availability and use of dental and maxillofacial emergency algorithms in Swiss hospitals. A survey was performed among physicians at Swiss emergency departments (ED) and participants of the “36th Annual Meeting of the Society for Oral and Cranio-Maxillofacial Surgery”. Eighty-nine EDs in Switzerland were questioned about the availability and use of electronic algorithms in their hospitals. Eighty-one (91%) participated in the study. In 75 (93%) of the EDs, electronic algorithms are used, mainly “medStandards”. Six have no available algorithms. Fifty-two (64%) use algorithms daily. Eight (10%) Swiss EDs have maxillofacial and dental algorithms, and 73 (90%) have no access to or do not know about them. For dental algorithms, 28 (38%) of the respondents would like to have access, and 16 (22%) do not desire access. For maxillofacial algorithms, 23 (32%) want to have access and 21 (29%) do not want it. Most (74%) of the participating maxillofacial surgeons did not know about the existence of ED algorithms regarding their specialty. Our study shows that the existence of specific algorithms is often not known. Furthermore, there is a demand for dental and maxillofacial algorithms in Swiss EDs.