A patient presenting with an infected diabetic foot ulcer and Staphylococcus aureus chronic osteomyelitis was studied to validate the clinical importance of bacterial colonization of osteocytic-canalicular networks, as we recently reported in a mouse model. We utilized transmission electron microscopy to describe the deformation of S. aureus, from round cocci to rod-shaped bacteria, in the submicron osteocytic-canalicular networks of amputated bone tissue.
To our knowledge, this is the first evidence of S. aureus deformation and invasion of the osteocytic-canalicular system in human bone, which supports a new mechanism of persistence in the pathogenesis of chronic osteomyelitis.

The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) system plays an important role in angiogenesis and osteogenesis during both skeletal development and postnatal bone growth and repair. Indeed, protein expression changes of this system could contribute to craniofacial defects commonly associated with a variety of congenital syndromes. Similarly to other craniofacial bones, mandible arises from neural crest cells of the neuroectodermal germ layer, and undergoes membranous ossification. Here, we report a case of left mandibular hypoplasia in a 42-year-old man treated with autologous bone graft from mandibular symphysis. After 3 months from surgical reconstruction, the protein expression of VEGF and receptors (VEGFR-1, -2 and -3) in regenerated bone tissue was evaluated by immunohistochemistry. At variance with the mandibular symphysis bone harvested for graft surgery, we observed de novo expression of VEGF and VEGFRs in osteoblasts and osteocytes from post-graft regenerating mandible bone tissue. In particular, while VEGFR-1 and VEGFR-3 immunopositivity was widespread in osteoblasts, that of VEGFR-2 was scattered. Among the three receptors, VEGFR-3 was the more intensively expressed both in osteoblasts and osteocytes. These findings suggest that VEGFR-2 might be produced during the early period of regeneration, while VEGFR-1 might participate in bone cell maintenance during the middle or late consolidation period. VEGFR-3 might, instead, represent a specific signal for ectomesenchymal lineage differentiation during bone regeneration. Modulation of VEGF/VEGFR signaling could contribute to graft integration and new bone formation during mandibular regeneration.

Osteocytes are hypothesized to regulate bone remodeling guided by both biological and mechanical stimuli. Morphology of the lacunar-canalicular network of osteocytes has been hypothesized to be strongly related to the level of mechanical loading and to various bone diseases. Finite element modeling could help to better understand the mechanosensation process by predicting the physiological strain environment. The aims of this study were to (i) quantify the lacunar-canalicular morphology in the cortex of the human femur; (ii) predict the in situ local deformations around and in osteocytes by means of case-specific finite element models; and (iii) investigate the potential relationship between morphology and deformations. Human femoral cortical bone samples were imaged using synchrotron X-ray phase nano-tomography with 50 nm voxel size. Rectangular volumes of interest were selected to contain single osteocyte lacunae and the surrounding matrix. Lacunar-canalicular morphology was quantified and the cell geometry was artificially reconstructed based on a priori assumptions. Finite element models of the volumes of interest were generated, containing the extracellular matrix, osteocyte and peri-cellular matrix, and subjected to uniaxial compression. The morphological analysis revealed that canalicular number was dictated by lacunar size, that the spacing of canaliculi fell within a narrow range, suggesting that these pores are well distributed throughout the bone matrix and indicated the trend that lacunae at the outer osteon boundary were less elongated than others. No apparent relationship was found between the morphological parameters and the predicted strains. The globally applied strain was amplified locally by factors up to 10 and up to 70 in the extracellular matrix and the in cells, respectively. Cell deformations were localized mainly at the body-dendrite junctions, with magnitudes reaching the in vitro stimulatory threshold reported for osteocytes.

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Basic issues surrounding osteocyte biology are still poorly understood, including the variability of osteocyte morphology within and among bones, individuals, and species. Several studies have suggested that the volume or shape of osteocytes (or their lacunae) is related to bone and/or organismal growth rate or metabolism, but the nature of this relationship, if any, is unclear. Furthermore, several studies have linked osteocyte lacuna volume with genome size or growth rate and suggested that osteocyte lacuna volume is unrelated to body size. Herein the scaling of osteocyte lacuna volume with body mass, growth and basal metabolic rates, genome size, and red blood cell size is examined using a broad sample of extant birds within a phylogenetic framework. Over 12,000 osteocyte lacuna axes were measured in a variety of bones from 34 avian and four non-avian dinosaur species. Osteocyte lacunae in parallel-fibered bone are scalene ellipsoids; their morphology and volume cannot be reliably estimated from any single thin section, and using a prolate ellipsoid model to estimate osteocyte lacuna volume results in a substantial (ca. 2-7 times) underestimate relative to true lacunar volume. Orthogonal thin sections reveal that in birds, even when only observing parallel-fibered, primary, cortical bone, intra-skeletal variation in osteocyte lacuna volume and shape is very high (volumes vary by a factor of 5.4 among different bones), whereas variation among homologous bones of the same species is low (1.2-44%; mean=12%). Ordinary and phylogenetically informed bivariate and multiple regressions demonstrate that in birds, osteocyte volume scales significantly but weakly with body mass and mass-specific basal metabolic rate and moderately with genome size, but not with erythrocyte size. Avian whole-body growth rate and osteocyte lacuna volume are weakly and inversely related. Finally, we present the first three-dimensionally calculated osteocyte volumes for several non-avian dinosaurs, which are much larger than previously reported values and smaller than those of large extant avians. Osteocyte volumes estimated from a single transverse section and assuming prolate morphology, as done in previous studies, are relative underestimates in theropod dinosaurs compared to sauropod dinosaurs, raising the possibility that no major change in osteocyte volumes (and genome size) occurred within Theropoda on the lineage leading to birds. Osteocyte volume is intertwined with several organismal attributes whose relative importance varies at a number of hierarchical levels.

The objective of this proof-of-principle multicenter case series was to examine the bone regenerative potential of a newly introduced equine-derived bone mineral matrix (Equimatrix) to provide human sinus augmentation for the purpose of implant placement in the posterior maxilla. There were 10 patients requiring 12 maxillary sinus augmentations enrolled in this study. Histologic results at 6 months demonstrated abundant amounts of vital new bone in intimate contact with residual graft particles. Active bridging between residual graft particles with newly regenerated bone was routinely observed in intact core specimens. A mean value of 23.4% vital bone formation was observed at 6 months. This compared favorably with previous results using xenografts to produce bone in the maxillary sinus for the purpose of dental implant placement. Both the qualitative and quantitative results of this case series suggest comparable bone regenerative results at 6 months to bovine-derived xenografts.

OBJECTIVE: To evaluate its efficacy and predictability in immediate extraction sockets, this case series used demineralized bone matrix in a puttylike carrier (DBM putty) with and without mineralized bone chips. Each preparation was made from the long bones of the same tissue donor; the only excipient material was water.
METHODS: A single failing tooth was atraumatically extracted from each study subject, and the socket was debrided. Intact sockets were grafted with DBM putty (n = 6), and sockets with buccal defects were grafted with DBM putty with bone chips (n = 6). A bovine pericardium membrane was draped over the graft site, and tension-free primary closure was obtained. After 6 months of healing, a trephine biopsy was taken from the center of each graft, and then, a dental implant was placed. Two subjects were withdrawn, and histologic data could not be obtained from 2 other patients.
RESULTS: Mean new bone fill was 40.28% for DBM putty (n = 5) and 44.60% for DBM putty with bone chips (n = 4).
CONCLUSIONS: Both preparations maintained ridge dimensions and, despite ongoing bone turnover, produced adequate mineralized tissue that enabled implant placement at 6 months. This finding warrants further research.

An implant that had penetrated the nasal cavity of a 53-year-old woman was removed after 10 months. The implant had a resorbable blast media surface and an external connection. Histomorphometric evaluation showed that the mean bone-implant contact ratio was 88.08%, and excellent osseointegration was observed. The mean bone fill between threads was 78.46%.

Among the graft materials that can be used clinically, xenografts are the most common. Xenografts are of bovine, porcine, or equine origin and require the complete removal of proteins to avoid immunologic problems and the risk of transmission of prions, viruses, etc. Protein destruction can be achieved by a chemical procedure using organic solvents and heat treatment. After this process, a carbonated hydroxyapatite similar to human bone remains. The aim of this case report is to investigate the bone formation in a sinus augmentation procedure using a high temperature-treated bovine porous hydroxyapatite. A 58-year-old woman underwent bilateral sinus augmentation using this biomaterial. After 9 months, during stage-two surgery, two core biopsy specimens were retrieved and treated to obtain thin ground undecalcified sections. Microscopically, newly formed bone was present at the interface with most particles. The major portion of the particles appeared to be completely lined and surrounded by bone. No obvious signs of resorption were present on the biomaterial surface. No gaps or connective tissue were present at the bone-biomaterial interface. No inflammatory infiltrate or fibrous encapsulation of the particles was present. Histomorphometry showed that the percentages of newly formed bone, residual grafted particles, and marrow spaces were 25.1% ± 2.3%, 37.3% ± 1.1%, and 38.5% ± 3.1%, respectively. The excellent properties demonstrated by Endobon are probably a result of its particular hydroxyapatite porous microstructure with a high percentage of interconnected micropores that promote the ingrowth of osteogenic cells and vessels, making graft integration easier and faster.

A pink retained left mandibular first molar without carious lesions was diagnosed in a healthy 12-year-old girl presenting normal clinical tests. An orthopantomogram failed to detect other retained teeth. Both periapical radiography and computed tomography showed the absence of a periodontal ligament space in the bifurcation area and the presence of radiolucency or calcifications in the pulp cavity. The coronal part of the removed tooth was subjected to histological and immunohistochemical analysis using anti-PCNA (proliferation marker) and anti-p53 (apoptosis marker) antibodies. Root surfaces were observed by scanning electron microscopy. The pink color of the molar reflected the extension of resorptive tissue into the clinical crown and the underlining proliferation of pulp vessels. Ankylosis observed in the bifurcation area was also detected in the coronal part of the pulp. Whereas odontoblasts secreted tertiary dentin despite no evidence for a carious lesion, only osteocytes in the newly formed bone were apoptotic and the root surfaces were free of resorption lacunae. The etiopathology of the lesion in this case indicated a pulp origin, suggesting that new therapies targeting this tissue should be developed.