Elastogenic cues and methods for using same

Disclosed are elastogenic cues that can be utilized to encourage growth and development of elastin-containing cellular constructs. The elastogenic cues include hyaluronan fragments and oligomers, optionally in conjunction with growth factors and/or a source of copper ions. The elastogenic cues can up-regulate elastin matrix synthesis and by vascular smooth muscle cells. In addition to encouraging synthesis of elastin in a cellular matrix and organization into elastic fibers, the elastogenic cues can also stabilize the formed ECM matrix through suppression of elastin-laminin receptor (ELR). In addition, the elastogenic cues can inhibit cell hyper-proliferation (e.g., hyperplasia) common in inflammatory vascular disease

Physiologic compliance in engineered small-diameter arterial constructs based on an elastomeric substrate.

Compliance mismatch is a significant challenge to long-term patency in small-diameter bypass grafts because it causes intimal hyperplasia and ultimately graft occlusion. Current engineered grafts are typically stiff with high burst pressure but low compliance and low elastin expression. We postulated that engineering small arteries on elastomeric scaffolds under dynamic mechanical stimulation would result in strong and compliant arterial constructs. This study compares properties of engineered arterial constructs based on biodegradable polyester scaffolds composed of either rigid poly(lactide-co-glycolide) (PLGA) or elastomeric poly(glycerol sebacate) (PGS). Adult baboon arterial smooth muscle cells (SMCs) were cultured in vitro for 10 days in tubular, porous scaffolds. Scaffolds were significantly stronger after culture regardless of material, but the elastic modulus of PLGA constructs was an order of magnitude greater than that of porcine carotid arteries and PGS constructs. Deformation was elastic in PGS constructs and carotid arteries but plastic in PLGA constructs. Compliance of arteries and PGS constructs were equivalent at pressures tested. Altering scaffold material from PLGA to PGS significantly decreased collagen content and significantly increased insoluble elastin content in constructs without affecting soluble elastin concentration in the culture medium. PLGA constructs contained no appreciable insoluble elastin. This research demonstrates that: (1) substrate stiffness directly affects in vitro tissue development and mechanical properties; (2) rigid materials likely inhibit elastin incorporation into the extracellular matrix of engineered arterial tissues; and (3) grafts with physiologic compliance and significant elastin content can be engineered in vitro after only days of cell culture

3D Hepatic Cultures Simultaneously Maintain Primary Hepatocyte and Liver Sinusoidal Endothelial Cell Phenotypes

Developing in vitro engineered hepatic tissues that exhibit stable phenotype is a major challenge in the field of hepatic tissue engineering. However, the rapid dedifferentiation of hepatic parenchymal (hepatocytes) and non-parenchymal (liver sinusoidal endothelial, LSEC) cell types when removed from their natural environment in vivo remains a major obstacle. The primary goal of this study was to demonstrate that hepatic cells cultured in layered architectures could preserve or potentially enhance liver-specific behavior of both cell types. Primary rat hepatocytes and rat LSECs (rLSECs) were cultured in a layered three-dimensional (3D) configuration. The cell layers were separated by a chitosan-hyaluronic acid polyelectrolyte multilayer (PEM), which served to mimic the Space of Disse. Hepatocytes and rLSECs exhibited several key phenotypic characteristics over a twelve day culture period. Immunostaining for the sinusoidal endothelial 1 antibody (SE-1) demonstrated that rLSECs cultured in the 3D hepatic model maintained this unique feature over twelve days. In contrast, rLSECs cultured in monolayers lost their phenotype within three days. The unique stratified structure of the 3D culture resulted in enhanced heterotypic cell-cell interactions, which led to improvements in hepatocyte functions. Albumin production increased three to six fold in the rLSEC-PEM-Hepatocyte cultures. Only rLSEC-PEM-Hepatocyte cultures exhibited increasing CYP1A1/2 and CYP3A activity. Well-defined bile canaliculi were observed only in the rLSEC-PEM-Hepatocyte cultures. Together, these data suggest that rLSEC-PEM-Hepatocyte cultures are highly suitable models to monitor the transformation of toxins in the liver and their transport out of this organ. In summary, these results indicate that the layered rLSEC-PEM-hepatocyte model, which recapitulates key features of hepatic sinusoids, is a potentially powerful medium for obtaining comprehensive knowledge on liver metabolism, detoxification and signaling pathways in vitro

Design and Synthesis of Binding Growth Factors

Growth factors play important roles in tissue regeneration. However, because of their instability and diffusible nature, improvements in their performance would be desirable for therapeutic applications. Conferring binding affinities would be one way to improve their applicability. Here we review techniques for conjugating growth factors to polypeptides with particular affinities. Conjugation has been designed at the level of gene fusion and of polypeptide ligation. We summarize and discuss the designs and applications of binding growth factors prepared by such conjugation approaches

An Investigation into the electromagnetic behavior of the vector controlled induction motor drives

High performance a.c. drive applications require fast torque response. The field oriented mode of control also known as current vector control facilitates fast and desired torque response similar to that in d.c. drive systems. This thesis is based on the basic principles of vector control applied to induction motors...Radial and tangential components of the electromagnetic force in the airgap of a vector controlled induction machine have beeninvestigated. The study reveals the correlation between the average value and undulation of the force components to the sinusoidal stator currents in the synchronous reference frame --Abstract, page iii

Delivery of Mesenchymal Stem Cells from Gelatin–Alginate Hydrogels to Stomach Lumen for Treatment of Gastroparesis

Gastroparesis (GP) is associated with depletion of interstitial cells of Cajal (ICCs) and enteric neurons, which leads to pyloric dysfunction followed by severe nausea, vomiting and delayed gastric emptying. Regenerating these fundamental structures with mesenchymal stem cell (MSC) therapy would be helpful to restore gastric function in GP. MSCs have been successfully used in animal models of other gastrointestinal (GI) diseases, including colitis. However, no study has been performed with these cells on GP animals. In this study, we explored whether mouse MSCs can be delivered from a hydrogel scaffold to the luminal surfaces of mice stomach explants. Mouse MSCs were seeded atop alginate–gelatin, coated with poly-l-lysine. These cell–gel constructs were placed atop stomach explants facing the luminal side. MSCs grew uniformly all across the gel surface within 48 h. When placed atop the lumen of the stomach, MSCs migrated from the gels to the tissues, as confirmed by positive staining with vimentin and N-cadherin. Thus, the feasibility of transplanting a cell–gel construct to deliver stem cells in the stomach wall was successfully shown in a mice stomach explant model, thereby making a significant advance towards envisioning the transplantation of an entire tissue-engineered ‘gastric patch’ or ‘microgels’ with cells and growth factors

Employees loyalty, integrity and engagement in organisations

Successful and sustainable organizations consist of significant factors such as people, purpose of the organization, processes involved, physical resources and customers. This research paper concentrating on the people factor in a form of employee loyalty, integrity and engagement. Thus, the purpose of this paper is to investigate the relationship between employee loyalty, employee integrity and employee engagement. As for the design/methodology/approach, online survey forms questionnaire was used for collecting the study data from 135 employees who represent three managerial levels from both public and private sectors in Kota Kinabalu, Sabah, Malaysia. Eight (8) hypotheses were developed in order to test the said relationship. Hypotheses were tested through using various testes namely: the correlation coefficient and the regression analysis from the Statistical Package for Social Science software (SPSS). The findings indicated that there is a significant relationship between integrity and engagement. The study is limited to the facts that it is based on a small number of employees working mostly in one single organization which limits the generalizability of the results; a limitation that does not allow for statistical generalization but allows for analytical generalization. The study contributes to the literature of Employee Engagement and more specifically to the relationship between employee loyalty, integrity and engagement in the Kata Kinabalu, Sabah, Malaysia public and private sector. The outcome of the research draws decision makers' attention to the importance of employees' loyalty, integrity and its impact on their engagement