The effect of three hemostatic agents on early bone healing in an animal model

<p>Abstract</p> <p>Background</p> <p>Resorbable bone hemostasis materials, oxidized regenerated cellulose (ORC) and microfibrillar collagen (MFC), remain at the site of application for up to 8 weeks and may impair osteogenesis. Our experimental study compared the effect of a water-soluble alkylene oxide copolymer (AOC) to ORC and MFC versus no hemostatic material on early bone healing.</p> <p>Methods</p> <p>Two circular 2.7 mm non-critical defects were made in each tibia of 12 rabbits. Sufficient AOC, ORC or MFC was applied to achieve hemostasis, and effectiveness recorded. An autologous blood clot was applied to control defects. Rabbits were sacrificed at 17 days, tibiae excised and fixed. Bone healing was quantitatively measured by micro-computed tomography (micro-CT) expressed as fractional bone volume, and qualitatively assessed by histological examination of decalcified sections.</p> <p>Results</p> <p>Hemostasis was immediate after application of MFC and AOC, after 1-2 minutes with ORC, and >5 minutes for control. At 17 days post-surgery, micro-CT analysis showed near-complete healing in control and AOC groups, partial healing in the ORC group and minimal healing in the MFC group. Fractional bone volume was 8 fold greater in the control and AOC groups than in the MFC group (0.42 ± 0.06, 0.40 ± 0.03 vs 0.05 ± 0.01, <it>P </it>< 0.001) and over 1.5-fold greater than in the ORC group (0.25 ± 0.03, <it>P </it>< 0.05). By histology, MFC remained at the application site with minimal healing at the defect margins and early fibrotic tissue within the defect. ORC-treated defects showed partial healing but with early fibrotic tissue in the marrow space. Conversely, control and AOC-treated defects demonstrated newly formed woven bone rich in cellular activity with no evidence of AOC remaining at the application site.</p> <p>Conclusions</p> <p>Early healing appeared to be impaired by the presence of MFC and impeded by the presence of ORC. In contrast, AOC did not inhibit bone healing and suggest that AOC may be a better bone hemostatic material for procedures where bony fusion is critical and immediate hemostasis required.</p

Novel Oxysterols Have Pro-Osteogenic and Anti-Adipogenic Effects In Vitro and Induce Spinal Fusion In Vivo

ABSTRACT Stimulation of bone formation by osteoinductive materials is of great clinical importance in spinal fusion surgery, repair of bone fractures, and in the treatment of osteoporosis. We previously reported that specific naturally occurring oxysterols including 20(S)-hydroxycholesterol (20S) induce the osteogenic differentiation of pluripotent mesenchymal cells, while inhibiting their adipogenic differentiation. Here we report the characterization of two structural analogues of 20S, Oxy34 and Oxy49, which induce the osteogenic and inhibit the adipogenic differentiation of bone marrow stromal cells (MSC) through activation of Hedgehog (Hh) signaling. Treatment of M2-10B4 MSC with Oxy34 or Oxy49 induced the expression of osteogenic differentiation markers Runx2, Osterix (Osx), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN), as well as ALP enzymatic activity and robust mineralization. Treatment with oxysterols together with PPARg activator, troglitazone (Tro), inhibited mRNA expression for adipogenic genes PPARg, LPL, and aP2, and inhibited the formation of adipocytes. Efficacy of Oxy34 and Oxy49 in stimulating bone formation in vivo was assessed using the posterolateral intertransverse process rat spinal fusion model. Rats receiving collagen implants with Oxy 34 or Oxy49 showed comparable osteogenic efficacy to BMP2/collagen implants as measured by radiography, MicroCT, and manual inspection. Histological analysis showed trabecular and cortical bone formation by oxysterols and rhBMP2 within the fusion mass, with robust adipogenesis in BMP2-induced bone and significantly less adipocytes in oxysterol-induced bone. These data suggest that Oxy34 and Oxy49 are effective novel osteoinductive molecules and may be suitable candidates for further development and use in orthopedic indications requiring local bone formation

Article Novel Oxysterols Have Pro-Osteogenic and Anti-Adipogenic Effects In Vitro and Induce Spinal Fusion In Vivo

Histological analysis showed trabecular and cortical bone formation by oxysterols and rhBMP2 within the fusion mass, with robust adipogenesis in BMP2-induced bone and significantly less adipocytes in oxysterol-induced bone. These data suggest that Oxy34 and Oxy49 are effective novel osteoinductive molecules and may be suitable candidates for further development and use in orthopaedic indications requiring local bone formation

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-beta-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation The main risk factors for CRE infections in hospitals with high incidence included previous coloni-zation, urinary catheter and exposure to broad spectrum antibiotics

Life Cycle Assessment of Maize-Germ Oil Production and the Use of Bioenergy to Mitigate Environmental Impacts: A Gate-To-Gate Case Study

The need to reduce the environmental impacts of the food industry is increasing together with the dramatic increment of global food demand. Circulation strategies such as the exploitation of self-produced renewable energy sources can improve ecological performances of industrial processes. However, evidence is needed to demonstrate and characterize such environmental benefits. This study assessed the environmental performances of industrial processing of maize edible oil, whose energy provision is guaranteed by residues biomasses. A gate-to-gate Life Cycle Assessment (LCA) approach was applied for a large-size factory of Northern Italy to describe: (i) the environmental impacts related to industrial processing and (ii) the contribution of residue-based bioenergy to their mitigation, through the comparison with a reference system based on conventional energy. The results showed that oil refinement is the most impacting phase for almost all the considered impact categories. The use of residue-based bioenergy was found to drastically reduce the emissions for all the impact categories. Moreover, Cumulative Energy Demand analysis revealed that the use of biomass residues increased energy efficiency through a reduction of the total energy demand of the industrial process. The study demonstrates that the exploitation of residue-based bioenergy can be a sustainable solution to improve environmental performances of the food industry, while supporting circular economy

Deletion of Orai1 leads to bone loss aggravated with aging and impairs function of osteoblast lineage cells

Osteoblast lineage cells, a group of cells including mesenchymal progenitors, osteoblasts, and osteocytes, are tightly controlled for differentiation, proliferation and stage-specific functions in processes of skeletal development, growth and maintenance. Recently, the plasma membrane calcium channel Orai1 was highlighted for its role in skeletal development and osteoblast differentiation. Yet the roles of Orai1 in osteoblast lineage cells at various stages of maturation have not been investigated. Herein we report the severe bone loss that occurred in Orai1−/− mice, aggravated by aging, as shown by the microcomputed tomography (mCT) and bone histomorphometry analysis of 8-week and 12-week old Orai1−/− mice and sex-matched WT littermates. We also report that Orai1 deficiency affected the differentiation, proliferation, and type I collagen secretion of primary calvarial osteoblasts, mesenchymal progenitors, and osteocytes in Orai1−/− mice; specifically, our study revealed a significant decrease in the expression of osteocytic genes Fgf23, DMP1 and Phex in the cortical long bone of Orai1−/− mice; a defective cellular and nuclear morphology of Orai1−/− osteocytes; and defective osteogenic differentiation of Orai1−/− primary calvarial osteoblasts (pOBs), including a decrease in extracellular-secretion of type I collagen. An increase in the mesenchymal progenitor population of Orai1−/− bone marrow cells was indicated by a colony forming unit-fibroblasts (CFU-F) assay, and the increased proliferation of Orai1−/− pOBs was indicated by an MTT assay. Notably, Orai1 deficiency reduced the nuclear localization and transcription activity of the Nuclear Factor of Activated T-cell c1 (NFATc1), a calcium-regulated transcription factor, in pOBs. Altogether, our study demonstrated the crucial role of Orai1 in bone development and maintenance, via its diverse effects on osteoblast lineage cells from mesenchymal progenitors to osteocytes. Keywords: Orai1, Osteoblast lineage cells, Bone, Knockout mic