Usefulness of a Nanostructured Fibrin-Agarose Bone Substitute in a Model of Severely Critical Mandible Bone Defect

Critical defects of the mandibular bone are very difficult to manage with currently available materials and technology. In the present work, we generated acellular and cellular substitutes for human bone by tissue engineering using nanostructured fibrin–agarose biomaterials, with and without adipose-tissue-derived mesenchymal stem cells differentiated to the osteogenic lineage using inductive media. Then, these substitutes were evaluated in an immunodeficient animal model of severely critical mandibular bone damage in order to assess the potential of the bioartificial tissues to enable bone regeneration. The results showed that the use of a cellular bone substitute was associated with a morpho-functional improvement of maxillofacial structures as compared to negative controls. Analysis of the defect site showed that none of the study groups fully succeeded in generating dense bone tissue at the regeneration area. However, the use of a cellular substitute was able to improve the density of the regenerated tissue (as determined via CT radiodensity) and form isolated islands of bone and cartilage. Histologically, the regenerated bone islands were comparable to control bone for alizarin red and versican staining, and superior to control bone for toluidine blue and osteocalcin in animals grafted with the cellular substitute. Although these results are preliminary, cellular fibrin–agarose bone substitutes show preliminary signs of usefulness in this animal model of severely critical mandibular bone defect.

Evidence for osteocyte-mediated bone-matrix degradation associated with periprosthetic joint infection (PJI)

Osteomyelitis associated with periprosthetic joint infection (PJI) signals a chronic infection and the need for revision surgery. An osteomyelitic bone exhibits distinct morphological features, including evidence for osteolysis and an accelerated bone remodelling into poorly organised, poor-quality bone. In addition to immune cells, various bone cell-types have been implicated in the pathology. The present study sought to determine the types of bone-cell activities in human PJI bones. Acetabular biopsies from peri-implant bone from patients undergoing revision total hip replacement (THR) for chronic PJI (with several identified pathogens) as well as control bone from the same patients and from patients undergoing primary THR were analysed. Histological analysis confirmed that PJI bone presented increased osteoclastic activity compared to control bone. Analysis of osteocyte parameters showed no differences in osteocyte lacunar area between the acetabular bone taken from PJI patients or primary THR controls. Analysis of bone matrix composition using Masson’s trichrome staining and second-harmonic generation microscopy revealed widespread lack of mature collagen, commonly surrounding osteocytes, in PJI bone. Increased expression of known collagenases, such as matrix metallopeptidase (MMP) 13, MMP1 and cathepsin K (CTSK), was measured in infected bone compared to non-infected bone. Human bone and cultured osteocyte-like cells experimentally exposed to Staphylococcus aureus exhibited strongly upregulated expression of MMP1, MMP3 and MMP13 compared to non-exposed controls. In conclusion, the study identified previously unrecognised bone-matrix changes in PJI caused by multiple organisms deriving from osteocytes. Histological examination of bone collagen composition may provide a useful adjunct diagnostic measure of PJI.

Expression of circulating Mir-139-5p is associated with Postmenopausal Osteoporosis in Indian women

Background: Osteoporosis in post-menopausal women is known to progress periodically and is highly associated with inflammation. MicroRNAs regulate inflammatory process, which may therefore control bone metabolism. Deregulation of miRNAs associated with inflammation may lead to development and progression of osteoporosis. We selected four miRNAs known to be involved in inflammation to test their association with post-menopausal osteoporosis. Methods: We quantified four circulating miRNAs, hsa-miR-139-5p, hsa-miR-342-3p, hsa-miR-146a and hsa-miR-24-3p in plasma samples of 25 post-menopausal osteoporosis and 25 post-menopausal healthy subjects. Related biochemical tests were done using Cobas e411 and ELISA. Results: Upon quantification of circulating miRNAs, we observed that hsa-miR-139-5p was expressed higher in post-menopausal osteoporotic samples (p=0.01). The expression of hsa-miR-24-3p was seen lower in osteoporotic samples though not highly significant (p=0.2). Conclusion: Differential expression of hsa-miR-139-5p and hsa-miR-24-3p was seen in osteoporosis subjects. These miRNA could be significantly involved in development and progression of osteoporosis. Further studies are required to highlight miRNAs’ involvement in regulating bone metabolism, which could be manipulated to use them as marker or therapeutic strategies to alleviate osteoporosis.

Dimensional Accuracy of 3D-printed Models of the Right First Metacarpal Bones of Cadavers

Background. The use of 3D printing in medical education, prosthetics, and preoperative planning requiresdimensional accuracy of the models compared to the replicated tissues or organs.Objective. To determine the dimensional accuracy of 3D-printed models replicated from metacarpal bones fromcadavers. Methods. Fifty-two models were 3D-printed using fused deposition modeling (FDM), stereolithography (SLA),digital light processing (DLP), and binder jetting method from 13 right first metacarpal bones of cadavers fromthe College of Medicine, University of the Philippines Manila. Six dimensional parameters of the 3D-printedmodels and their control bones were measured using 0.01 mm calipers — length, midshaft diameter, base width,base height, head width, and head height. Mean measurements were compared using non-inferiority testing andmultidimensional scaling. Results. Mean measurements of the 3D-printed models were slightly larger than their control bones (standarddeviation range: 1.219-4.264; standard error range, 0.338-1.183). All models were found to be at least 90% accurateand statistically non-inferior compared to control bones. DLP-printed models were the most accurate (base width,99.62 %) and most similar to their control bone (–0.05, 90% CI –0.34, 0.24). Through multidimensional scaling,DLP-printed models (coordinate = 0.437) were the most similar to the control bone (coordinate = 0.899). Conclusion. The 3D-printed models are dimensionally accurate when compared to bones.

How Physical Activity across the Lifespan Can Reduce the Impact of Bone Ageing: A Literature Review

Bone remodeling is a lifelong process, due to the balanced activity of the osteoblasts (OBs), the bone-forming cells, and osteoclasts (OCs), the bone-resorbing cells. This equilibrium is mainly regulated by the WNT-ß-cathenin pathway and the RANK-RANKL/OPG system, respectively. Bone ageing is a process which normally occurs during life due to the imbalance between bone formation and bone resorption, potentially leading to osteoporosis. Bone loss associated with bone ageing is determined by oxidative stress, the result of the increasing production of reactive oxygen species (ROS). The promotion of physical exercise during growth increases the chances of accruing bone and delaying the onset of osteoporosis. Several studies demonstrate that physical exercise is associated with higher bone mineral density and lower fracture incidence, and the resulting bone mineral gain is maintained with ageing, despite a reduction of physical activity in adulthood. The benefits of exercise are widely recognized, thus physical activity is considered the best non-pharmacologic treatment for pathologies such as osteoporosis, obesity, diabetes and cardiovascular disease. We reviewed the physiological mechanisms which control bone remodeling, the effects of physical activity on bone health, and studies on the impact of exercise in reducing bone ageing.