Long term performance evaluation of small-diameter vascular grafts based on polyvinyl alcohol hydrogel and dextran and MSCs-based therapies using the ovine pre-clinical animal model.

The functional and structural performance of a 5 cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA/Dx graft) associated to mesenchymal stem cells (MSCs)-based therapies and anticoagulant treatment with heparin, clopidogrel and warfarin was tested using the ovine model during the healing period of 24 weeks. The results were compared to the ones obtained with standard expanded polyetetrafluoroethylene grafts (ePTFE graft). Blood flow, vessel and graft diameter measurements, graft appearance and patency rate (PR), thrombus, stenosis and collateral vessel formation were evaluated by B-mode ultrasound, audio and color flow Doppler. Graft and regenerated vessels morphologic evaluation was performed by scanning electronic microscopy (SEM), histopathological and immunohistochemical analysis. All PVA/Dx grafts could maintain a similar or higher PR and systolic / diastolic laminar blood flow velocities were similar to ePTFE grafts. CD14 (macrophages) and α-actin (smooth muscle) staining presented similar results in PVA/Dx/MSCs and ePTFE graft groups. Fibrosis layer was lower and endothelial cells were only detected at graft-artery transitions where it was added the MSCs. In conclusion, PVA/Dx graft can be an excellent scaffold candidate for vascular reconstruction, including clinic mechanically challenging applications, such as SDVGs, especially when associated to MSCs-based therapies to promote higher endothelialization and lower fibrosis of the vascular prosthesis, but also higher PR values.

Strategic Orientations, Dynamic Capabilities, and Firm Performance: an Analysis for Knowledge Intensive Business Services

The strategic orientations of a firm are considered crucial for enhancing firm performance and their impact can be even greater when associated with dynamic capabilities, particularly in complex and dynamic environments. This study empirically analyzes the relationship between market, entrepreneurial and learning orientations, dynamic capabilities, and performance using an integrative approach hitherto little explored. Using a sample of 209 knowledge intensive business service firms, this paper applies structural equation modeling to explore both direct effects of strategic orientations and the mediating role of dynamic capabilities on performance. The study demonstrates that learning orientation and one of the dimensions of entrepreneurial orientation have a direct positive effect on performance. On the other hand, dynamic capabilities mediate the relationships between some of the strategic orientations and firm performance. Overall, when dynamic capabilities are combined with the appropriate strategic orientations, they enhance firm performance. This paper contributes to a better understanding of the knowledge economy, given the important role knowledge intensive business services play in such a dynamic and pivotal sector.