115 research outputs found
BMP2 and TGF-β Cooperate Differently during Synovial-Derived Stem-Cell Chondrogenesis in a Dexamethasone-Dependent Manner
Recent studies highlighting mesenchymal stem cell (MSC) epigenetic memory suggest that a different differentiation medium may be required depending on the tissue of origin. As synovial-derived stem cells (SDSCs) attract interest we aimed to investigate the influence of TGF-β1, BMP-2 and dexamethasone on SDSC chondrogenesis in vitro. We demonstrate that dexamethasone-free medium led to enhanced chondrogenic differentiation at both the mRNA and matrix level. The greatest COL2A1/COL10A1 ratio was detected in cells exposed to a combination medium containing 10 ng/mL BMP-2 and 1 ng/mL TGF-β1 in the absence of dexamethasone, and this was reflected in the total amount of glycosaminoglycans produced. In summary, dexamethasone-free medium containing BMP-2 and TGF-β1 may be the most suitable when using SDSCs for cartilage tissue regeneration
Alternative Geometries for 3D Bioprinting of Calcium Phosphate Cement as Bone Substitute
In the literature, many studies have described the 3D printing of ceramic-based scaffolds (e.g., printing with calcium phosphate cement) in the form of linear structures with layer rotations of 90°, although no right angles can be found in the human body. Therefore, this work focuses on the adaptation of biological shapes, including a layer rotation of only 1°. Sample shapes were printed with calcium phosphate cement using a 3D Bioplotter from EnvisionTec. Both straight and wavy spokes were printed in a round structure with 12 layers. Depending on the strand diameter (200 and 250 µm needle inner diameter) and strand arrangement, maximum failure loads of 444.86 ± 169.39 N for samples without subsequent setting in PBS up to 1280.88 ± 538.66 N after setting in PBS could be achieved
The trans-well coculture of human synovial mesenchymal stem cells with chondrocytes leads to self-organization, chondrogenic differentiation, and secretion of TGFβ
Erratum to: Clinical trial and in-vitro study comparing the efficacy of treating bony lesions with allografts versus synthetic or highly-processed xenogeneic bone grafts
About 3D printability of thermoplastic collagen for biomedical applications
With more than 1.5 million total knee and hip implants placed each year, there is an urgent need for a drug delivery system that can effectively support the repair of bone infections. Scaffolds made of natural biopolymers are widely used for this purpose due to their biocompatibility, biodegradability, and suitable mechanical properties. However, the poor processability is a bottleneck, as highly customizable scaffolds are desired. The aim of the present research is to develop a scaffold made of thermoplastic collagen (TC) using 3D printing technology. The viscosity of the material was measured using a rheometer. A 3D bioplotter was used to fabricate the scaffolds out of TC. The mechanical properties of the TC scaffolds were performed using tension/compression testing on a Zwick/Roell universal testing machine. TC shows better compressibility with increasing temperature and a decrease in dynamic viscosity (η), storage modulus (G'), and loss modulus (G″). The compressive strength of the TC scaffolds was between 3-10 MPa, depending on the geometry (cylinder or cuboid, with different infills). We have demonstrated for the first time that TC can be used to fabricate porous scaffolds by 3D printing in various geometries.The article processing charge was funded by the Baden-Wuerttemberg Ministry of Science,
Research and Art and the University of Freiburg in the funding program Open Access Publishing
Role of complement in in vitro and in vivo lung inflammatory reactions
Complement is one of the integral buttresses of the inflammatory response. In addition to host defense activities, proinflammatory properties of several complement components are described. This overview elucidates the role of complement in inflammatory reactions in vitro and in vivo, focusing on the complement activation products, C5a, and the membrane attack complex, C5b‐9. Using several approaches, the impact of these complement components in mechanisms relevant to neutrophil recruitment is emphasized. In addition, the participation of complement in endothelial superoxide generation and its essential requirement for full expression of lung injury is demonstrated, as are the involved intracellular signal transduction pathways. Understanding the mechanisms of complement‐induced proinflammatory effects may provide a basis for future therapeutic blockade of complement and/or its activation products. J. Leukoc. Biol. 64: 40–48; 1998.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142061/1/jlb0040.pd
Prospective Clinical Trial for Septic Arthritis:Cartilage Degradation and Inflammation Are Associated with Upregulation of Cartilage Metabolites
Background. Intra-articular infections can rapidly lead to osteoarthritic degradation. The aim of this clinical biomarker analysis was to investigate the influence of inflammation on cartilage destruction and metabolism. Methods. Patients with acute joint infections were enrolled in a prospective clinical trial and the cytokine composition of effusions (n=76) was analyzed. Characteristics of epidemiology and disease severity were correlated with levels of cytokines with known roles in cartilage turnover and degradation. Results. Higher synovial IL-1β concentrations were associated with clinical parameters indicating a higher disease severity (p<0.03) excluding the incidence of sepsis. Additionally, intra-articular IL-1β levels correlated with inflammatory serum parameters as leucocyte counts (LC) and C-reactive protein concentrations (p<0.05) but not with age or comorbidity. Both higher LC and synovial IL-1β levels were associated with increased intra-articular collagen type II cleavage products (C2C) indicating cartilage degradation. Joints with preinfectious lesions had higher C2C levels. Intra-articular inflammation led to increased concentrations of typical cartilage metabolites as bFGF, BMP-2, and BMP-7. Infections with Staphylococcus species induced higher IL-1β expression but less cartilage destruction than other bacteria. Conclusion. Articular infections have bacteria-specific implications on cartilage metabolism. Collagen type II cleavage products reliably mark destruction, which is associated with upregulation of typical cartilage turnover cytokines. This trial is registered with DRKS00003536, MISSinG
In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells.
Low back pain is a clinically highly relevant musculoskeletal burden and is associated with inflammatory as well as degenerative processes of the intervertebral disc. However, the pathophysiology and cellular pathways contributing to this devastating condition are still poorly understood. Based on previous evidence, we hypothesize that tissue renin-angiotensin system (tRAS) components, including the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), are present in human nucleus pulposus (NP) cells and associated with inflammatory and degenerative processes. Experiments were performed with NP cells from four human donors. The existence of angiotensin II, angiotensin II type 1 receptor (AGTR1), AGTR2, MAS-receptor (MasR), and ACE2 in human NP cells was validated with immunofluorescent staining and gene expression analysis. Hereafter, the cell viability was assessed after adding agonists and antagonists of the target receptors as well as angiotensin II in different concentrations for up to 48 h of exposure. A TNF-α-induced inflammatory in vitro model was employed to assess the impact of angiotensin II addition and the stimulation or inhibition of the tRAS receptors on inflammation, tissue remodeling, expression of tRAS markers, and the release of nitric oxide (NO) into the medium. Furthermore, protein levels of IL-6, IL-8, IL-10, and intracellular as well as secreted angiotensin II were assessed after exposing the cells to the substances, and inducible nitric oxide synthase (iNOS) levels were evaluated by utilizing Western blot. The existence of tRAS receptors and angiotensin II were validated in human NP cells. The addition of angiotensin II only showed a mild impact on gene expression markers. However, there was a significant increase in NO secreted by the cells. The gene expression ratios of pro-inflammatory/anti-inflammatory cytokines IL-6/IL-10, IL-8/IL-10, and TNF-α/IL-10 were positively correlated with the AGTR1/AGTR2 and AGTR1/MAS1 ratios, respectively. The stimulation of the AGTR2 MAS-receptor and the inhibition of the AGTR1 receptor revealed beneficial effects on the gene expression of inflammatory and tissue remodeling markers. This finding was also present at the protein level. The current data showed that tRAS components are expressed in human NP cells and are associated with inflammatory and degenerative processes. Further characterization of the associated pathways is warranted. The findings indicate that tRAS modulation might be a novel therapeutic approach to intervertebral disc disease
Prevention of bone disease and early detection of impending fractures in multiple myeloma patients can reduce morbidity and mortality: the necessity of interdisciplinary state-of-the-art treatment
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