Endogenous Modulation of Extracellular Matrix Collagen during Scar Formation after Myocardial Infarction

Myocardial infarction is remains the leading cause of death in developed countries. Recent data show that the composition of the extracellular matrix might differ despite similar heart function and infarction sizes. Because collagen is the main component of the extracellular matrix, we hypothesized that changes in inflammatory cell recruitment influence the synthesis of different collagen subtypes in myofibroblasts, thus changing the composition of the scar. We found that neutrophils sustain the proliferation of fibroblasts, remodeling, differentiation, migration and inflammation, predominantly by IL-1 and PPARγ pathways (n = 3). They also significantly inhibit the mRNA expression of fibrillar collagen, maintaining a reduced stiffness in isolated myofibroblasts (n = 4–5). Reducing the neutrophil infiltration in CCR1^−/− resulted in increased mRNA expression of collagen 11, moderate expression of collagen 19 and low expression of collagen 13 and 26 in the scar 4 weeks post infarction compared with other groups (n = 3). Mononuclear cells increased the synthesis of all collagen subtypes and upregulated the NF-kB, angiotensin II and PPARδ pathways (n = 3). They increased the synthesis of collagen subtypes 1, 3, 5, 16 and 23 but reduced the expression of collagens 5 and 16 (n = 3). CCR2^−/− scar tissue showed higher levels of collagen 13 (n = 3), in association with a significant reduction in stiffness (n = 4–5). Upregulation of the inflammation-related genes in myofibroblasts mostly modulated the fibrillar collagen subtypes, with less effect on the FACIT, network-forming and globular subtypes (n = 3). The upregulation of proliferation and differentiation genes in myofibroblasts seemed to be associated only with the fibrillar collagen subtype, whereas angiogenesis-related genes are associated with fibrillar, network-forming and multiplexin subtypes. In conclusion, although we intend for our findings to deepen the understanding of the mechanism of healing after myocardial infarction and scar formation, the process of collagen synthesis is highly complex, and further intensive investigation is needed to put together all the missing puzzle pieces in this still incipient knowledge process.     

Loss of immunoreactivity for RTI40, a type I cell-specific protein in the alveolar epithelium of rat lungs with bleomycin-induced fibrosis

After lung injury, the epithelial cells lining the alveolar surface in rat lung show an altered distribution of several membrane proteins. Pulmonary fibrosis was induced by intratracheal administration of bleomycin into the lung of rats and the distribution of RTI40, a recently detected alveolar epithelial type I cell antigen, was examined, as well as the relationship between RTI40 and a type I cell-specific antigen recognized by the monoclonal antibody MEP-1 and the type I cell-binding lectin Bauhinia purpurea in serial sections and double stainings. Loss of RTI40 protein was observed in fibrotic lungs, particularly in areas with obliteration of alveoli. Pre-embedding immunoelectron microscopy confirmed this observation by detection of RTI40 protein in the alveolar lumen. Western blot analysis revealed elevated levels of RTI40 in the bronchoalveolar fluid of bleomycin-treated rats with a maximum at day 7 after treatment. Twenty-eight days after bleomycin application, the bronchoalveolar fluid contained three times the amount of RTI40 x mg protein(-1) of control lungs, as determined by semiquantitative dot blot. These results suggest RTI40 as a tool for the evaluation of alveolar epithelial type I cell behaviour during re-epithelialization processes.     

Fast Fatigue Testing of Spinal Implant Systems by the Load Stage Product (LSP)‐Test Method

The LSP test method was used to compare various surface treatments of spinal rods for dorsal spine implant systems. This test method allowed a fast testing. Result were given after one or two weeks in comparison to 6 to 8 months. Rods made of two different cp‐Titanium materials ( Ti‐2 and Ti‐4) were tested. Best results with a LSP value of 167 Mio. were achieved with Ti‐4 material, shot peened with steel balls and glass beads. In comparison the lowest LSP value showed 81 Mio with Ti‐2 material shot peened with glass beads only. This kind of high speed testing reduced the typical development period from two years to at least 6 months.     

A SCIENTIFIC FOUNDATION OF COLLABORATIVE ENGINEERING

Collaborative engineering is the practical application of collaboration sciences to the engineering domain. In today's highly connected technology-driven economy, the production industry must rely on the best practices of collaborative engineering to stay competitive when designing, manufacturing and operating complex machines, processes, and systems on a global scale. Despite its importance, collaborative engineering is currently more of a practiced art than a scientific discipline. A better understanding of how engineers should collaborate with all stakeholders to accomplish complex tasks that fulfill our increasing social responsibilities is a grand challenge. However, because we currently lack well-defined sciences of human collaboration, we must first establish a scientific foundation of collaborative engineering to develop this emerging field into a rigorous discipline. This paper reports on the CIRP community's collective efforts to establish such a scientific foundation according to the “Observation → Hypothesis → Theory” development pathway. Our objective is to spearhead the rigorous development of this new human-centered engineering discipline, so that useful knowledge can be generated to educate students and practical guidelines can be developed to enable engineers to become more productive collaboration leaders in the new global production industry.     

Covalent binding of placental derived proteins to silk fibroin improves schwann cell adhesion and proliferation

Schwann cells play a key role in peripheral nerve regeneration. Failure in sufficient formation of Büngner bands due to impaired Schwann cell proliferation has significant effects on the functional outcome after regeneration. Therefore, the growth substrate for Schwann cells should be considered with highest priority in any peripheral nerve tissue engineering approach. Due to its excellent biocompatibility silk fibroin has most recently attracted considerable interest as a biomaterial for use as conduit material in peripheral nerve regeneration. In this study we established a protocol to covalently bind collagen and laminin, which have been isolated from human placenta, to silk fibroin utilizing carbodiimide chemistry. Altered adhesion, viability and proliferation of Schwann cells were evaluated. A cell adhesion assay revealed that the functionalization with both, laminin or collagen, significantly improved Schwann cell adhesion to silk fibroin. Moreover laminin drastically accelerated adhesion. Schwann cell proliferation and viability assessed with BrdU and MTT assay, respectively, were significantly increased in the laminin-functionalized groups. The results suggest beneficial effects of laminin on both, cell adhesion as well as proliferative behaviour of Schwann cells. To conclude, the covalent tailoring of silk fibroin drastically enhances its properties as a cell substratum for Schwann cells, which might help to overcome current hurdles bridging long distance gaps in peripheral nerve injuries with the use of silk-based nerve guidance conduits.     

An overview of power-law creep in polycrystalline β-titanium

A constitutive law for power-law creep of BCC β-Ti is developed, based on experimental data from eight independent studies. The present compilation adds more than twice as many data points as previous analyses, covers nine orders of magnitude in strain rate from 10⁻⁷ to 10² s⁻¹, and incorporates recent data for the shear modulus of β-Ti.     

The Structural Evolution and Densification Mechanisms of Nanophase Separation Sintering

Nanophase separation sintering (NPSS) facilitates low temperature, pressureless sintering through the formation of solid phase necks driven by phase separation. Systems that have been shown to exhibit this phenomenon are W–Cr, Cr–Ni and to a lesser degree Ti–Mg. Initial information on the average rate-limiting sintering kinetics in these systems was obtained using traditional master sintering curve analysis, but it is very clear that multiple processes occur during NPSS, and these should each have their own characteristic kinetics. Here we analyze these three systems in greater kinetic detail using densification rates in a Kissinger-style analysis derived explicitly for densification data. For the W–Cr and Cr–Ni systems two critical temperatures were identified: one at low temperatures for the formation of the secondary phase necks, and a second one at high temperatures corresponding to the onset of rapid densification. The activation energies of these processes are different, and reflective of bulk solute diffusion and interdiffusion, respectively. Combined with microstructural observations, these data show that the onset of rapid densification at high temperatures is facilitated by the presence of the second-phase necks, and occurs at the point where the system can fully interdiffuse, rehomogenizing those necks. These observations help explain why the Ti–Mg system does not densify well, because it does not exhibit redissolution at high temperatures. These results help clarify the conditions needed to achieve NPSS and may support design of new alloys for NPSS behavior.

     

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