A flow visualization study of an anatomic coronary artery anastomosis model with an implant.

Flow Streamlining Devices is a new tool in Coronary Artery Bypass Grafting (CABG). They aim in: a) Performing a sutureless anastomosis to reduce thrombosis at the veno-arterial junction, and b) Providing a hemodynamically efficient scaffolding to reduce secondary flow disturbances. Thrombosis and flow disturbances are factors that have been reported as contributing factors to the development of intimal hyperplasia (IH) and failure of the graft. By reducing thrombosis and flow disturbances, it is expected that IH will be inhibited and the lifetime of the graft extended. To evaluate the hemodynamic benefits of such an implant, two models were designed and fabricated. One simulated the geometry of the conventional anastomosis without an implant, and the other simulated an anastomosis with a flow streamlining implant. Identical flow conditions relevant to a coronary anastomosis were imposed on both models and flow visualization was performed with dye injection and a digital camera. Results showed reduction of disturbances in the presence of the implant. This reduction seems to be favorable to hemodynamic streamlining which may create conditions that may inhibit the initialization of IH. However, the compliance and geometric mismatch between the anastomosis and the implant created a disturbance at the rigid compliant wall interface, which should be eliminated prior to clinical applications.     

Bilateral field advantage in visual crowding

Thirty randomly oriented T’s were presented in a circle around fixation at an eccentricity of 11° such that each T was crowded by its neighbors. Two locations within the same hemifield (unilateral condition) or one location in each hemifield (bilateral condition) were precued for subsequent probing. Observers were then asked to report the orientation of a target T at one of these locations. A bilateral field advantage was found: target identification was better when the two precued targets were in different hemifields than when they were within the same hemifield. This bilateral advantage was absent when only targets were presented, without any distracters. Further controls showed that this advantage could not be attributed to differences between horizontal and vertical target alignments or to visual field anisotropies. A similar bilateral advantage has been reported for multiple object tracking (Alvarez, G. A., & Cavanagh, P. (2005). Independent resources for attentional tracking in the left and right visual fields. Psychological Science 16(8), 637-643) and other attentional tasks. Our results suggest that crowding also demonstrates separate attentional resources in the left and right hemifields. There was a cost to attending to two targets presented unilaterally over attending to a single target. However, this cost was reduced when the two crowded targets were in separate hemifields.     

Biocompatible nanofiber matrices for the engineering of a dermal substitute for skin regeneration

Natural and synthetic biodegradable nanofibers are extensively used for biomedical applications and tissue engineering. Biocompatibility and a well-established safety profile for polycaprolactone (PCL) and collagen represent a favorable matrix for preparing a dermal substitute for engineering skin. Collagen synthesized by fibroblasts is a good surface active agent and demonstrates its ability to penetrate a lipid-free interface. During granulation tissue formation, fibronectin provides a temporary substratum for migration and proliferation of cells and provides a template for collagen deposition, which increases stiffness and tensile strength of this healing tissues. The objective of this study was to fabricate nanofiber matrices from novel biodegradable PCL and collagen to mimic natural extracellular matrix (ECM) and to examine the cell behavior, cell attachment, and interaction between cells and nanofiber matrices. Collagen nanofiber matrices show a significant (p < 0.001) level of fibroblast proliferation and increase up to 54% compared with control tissue culture plate (TCP) after 72 h. The present investigation shows that PCL-coated collagen matrices are suitable for fibroblast growth, proliferation, and migration inside the matrices. This novel biodegradable PCL and collagen nanofiber matrices support the attachment and proliferation of human dermal fibroblasts and might have potential in tissue engineering as a dermal substitute for skin regeneration.     

Electrospun P(LLA-CL) nanofiber: a biomimetic extracellular matrix for smooth muscle cell and endothelial cell proliferation

Poly(L-lactide-co-epsilon-caprolactone) [P(LLA-CL)] with L-lactide to epsilon-caprolactone ratio of 75 to 25 has been electrospun into nanofibers. The relationship between electrospinning parameters and fiber diameter has been investigated. The fiber diameter decreased with decreasing polymer concentration and with increasing electrospinning voltage. The X-ray diffractometer and differential scanning colorimeter results suggested that the electrospun nanofibers developed highly oriented structure in CL-unit sequences during the electrospinning process. The biocompatibility of the nanofiber scaffold has been investigated by culturing cells on the nanofiber scaffold. Both smooth muscle cell and endothelial cell adhered and proliferated well on the P(LLA-CL) nanofiber scaffolds.     

Peripheral nerve regeneration by microbraided poly(L-lactide-co-glycolide) biodegradable polymer fibers

Tiny tubes with fiber architecture were developed by a novel method of fabrication upon introducing some modification to the microbraiding technique, to function as nerve guide conduit and the feasibility of in vivo nerve regeneration was investigated through several of these conduits. Poly(L-lactide-co-glycolide) (10:90) polymer fibers being biocompatible and biodegradable were used for the fabrication of the conduits. The microbraided nerve guide conduits (MNGCs) were characterized using scanning electron microscopy to study the surface morphology and fiber arrangement. Degradation tests were performed and the micrographs of the conduit showed that the degradation of the conduit is by fiber breakage indicating bulk hydrolysis of the polymer. Biological performances of the conduits were examined in the rat sciatic nerve model with a 12-mm gap. After implantation of the MNGC to the right sciatic nerve of the rat, there was no inflammatory response. One week after implantation, a thin tissue capsule was formed on the outer surface of the conduit, indicating good biological response of the conduit. Fibrin matrix cable formation was seen inside the MNGC after 1 week implantation. One month after implantation, 9 of 10 rats showed successful nerve regeneration. None of the implanted tubes showed tube breakage. The MNGCs were flexible, permeable, and showed no swelling apart from its other advantages. Thus, these new poly(L-lactide-co-glycolide) microbraided conduits can be effective aids for nerve regeneration and repair and may lead to clinical applications.     

Overexpression of Grb2 in inflammatory lesions and preneoplastic foci and tumors induced by N-nitrosodimethylamine in Helicobacter hepaticus-infected and -noninfected A/J mice

Growth factors bind to membrane receptor tyrosine kinases, resulting in autophosphorylation and subsequent binding to proteins with SH2 domains, including growth factor receptor-bound protein 2 (Grb2). Grb2 bridges receptors to tyrosine kinase substrates such as SHC and SOS, which in turn facilitate the activation of downstream signaling pathways, including Ras and mitogen-activated protein kinase (MAPK). Overexpression of Grb2 has been demonstrated in several types of neoplasia but has not been investigated in liver tumorigenesis. Here we investigated Grb2 expression in liver lesions in N-nitrosodimethylamine (NDMA)-treated Helicobacter hepaticus-infected and -noninfected A/J mice at 1 year of age. Previously, we reported (6) that infection promotes the development of these NDMA-initiated tumors. In controls, Grb2 immunostaining was absent from normal hepatic tissues, whereas the inflammatory lesions in infected livers were positive for cytoplasmic Grb2 in both hepatocytes and infiltrating leukocytes. All preneoplastic foci (7 of 7), 15 of 27 adenomas, and 3 of 7 carcinomas were positive for Grb2 by immunostaining in both infected and noninfected NDMA-initiated livers. Involvement of Grb2 was confirmed by immunoblotting of similarly infected mice at 9 to 18 months of age, showing a 2.5- to 3.3-fold increase in Grb2 protein in infected livers (p < 0.05 compared with uninfected controls) as well as in preneoplastic foci, adenomas, and carcinomas. These livers also showed a 2.5- to 2.8-fold increase in total Ras protein. The results suggest that upregulation of Grb2 is an early event in liver carcinogenesis, whether caused by the bacterial infection or by NDMA. Concomitant upregulation of Ras p21 would ensure transmission of amplified signal from growth factors via Grb2.     

Apolipoprotein E alters metabolism of AbetaPP in cells engaged in beta-amyloidosis

Canine smooth muscle cells (SMCs), cultured from amyloid-affected brain blood vessels accumulate Alzheimer amyloid-beta peptide (Abeta) intracellularly, either spontaneously or after treatment with apolipoprotein E (apoE). ApoE is codeposited with Abeta, which suggests that apoE participates in Abeta accumulation. We tested the hypothesis that apoE-induced accumulation of Abeta in SMCs is caused by an increased production of amyloid-beta precursor protein (AbetaPP) and/or its altered metabolism. We found that 24 hours of treatment with apoE3 or apoE4 induced intracellular accumulation of Abeta-immunoreactive deposits in SMCs but did not influence AbetaPP production and processing. The treatment with apoE3 or E4 for 3 days resulted in the following: increased Abeta-accumulation; reduced levels of secreted Abeta; increased production and cellular retention of mature AbetaPP770; and reduced culture growth, cell proliferation, and viability. ApoE4, but not apoE3, increased cellular levels of mRNA AbetaPP 770 (the main form produced in SMCs) about ninefold. ApoE3 stimulated production and cellular retention of endogenous apoE. We hypothesize that Abeta accumulation is triggered by apoE, which may bind and immobilize soluble Abeta produced in SMCs. The newly formed Abeta deposits may further accelerate Abeta accumulation by altering metabolism of AbetaPP.