Fabrication and in-vitro characterization of a polymeric aortic valve for minimally invasive valve replacement.

The valve replacement therapy is the standard treatment for severe heart valve diseases. Nowadays, two types of commercial prosthesis are available: mechanical and biological, but both of them have severe limitations. Moreover, alternative therapeutic approach for valve replacement, based on minimally invasive techniques (MIAVR), motivates the search for new valve materials. In this study a polyurethane-based self-expandable tri-leaflets heart valve compatible with MIAVR procedure is proposed. The device is based on the development, fabrication and characterization of three different elements: the leaflets, the polymeric stent for supporting the leaflets, and the external metallic stent for anchoring the valve to the native aortic root. The polymeric stent and the valve leaflets were fabricated using a thermoplastic silicone-polycarbonate-urethane using 3D printing and spray technology while the external metallic stent was made in nickel titanium (Nitinol) to obtain a self-expandable valve after the crimping process. The three elements were assembled in the completed device and tested by crimping, fatigue and fluid-dynamic test. The novel polymeric valve proposed showed promising results about valve crimping capabilities, durability and fluid dynamic performances. This approach could offer advantages such as low cost and to produce a tailor-made device basing on patient's imaging data. Moreover, the selected biomaterial offers the potential to have a device that could need of permanent anticoagulation and lack of calcification.

In vitro evaluation of the PEtU-PDMS material immunocompatibility: the influence of surface topography and PDMS content.

The aim of the present work is to evaluate the in vitro immunocompatibility of an elastomeric material with feasible applications in the cardiovascular field. In particular, since it is well known that surface chemistry and topography play a key role in the foreign body response, their influence on human monocytes was evaluated. The material, constituted by a poly(ether)urethane (PEtU) and a polydimethylsiloxane (PDMS), was synthesized to manufacture films and small-diameter vascular grafts with three different surface topographical features, smooth, rough and porous, and siloxane rates, 10, 30 and 40. Human THP-1 monocytes have been cultured for 72 h on the films and human blood has been circulating for 2 h into the grafts to assess leukocyte adhesion and cytokine releases. Materials extracts were utilized to evaluate monocyte apoptosis. Smooth films showed lower cell adhesion degrees than rough and porous ones. All the PEtU-PDMS (poly(ether)urethane-polydimethylsiloxane) films and vascular grafts induced a narrow inflammatory response, as demonstrated by slight cytokine secretion levels, in particular samples with the highest PDMS contents (30 and 40%) induced the lowest IL-1b secretion. Moreover, an absence of monocyte apoptosis advises that the negligible release values have not to be ascribed to material toxicity. In the end, surface topography showed to affect only monocyte adhesion while siloxane content the cytokine release. Therefore, the possibility to modify the above tested parameters during material synthesis and manufacture could allow to bound the inflammatory potency of the PEtU-PDMS devices and render them excellent candidates for cardiovascular reconstruction.

Silicone based polyurethane materials: a promising biocompatible elastomeric formulation for cardiovascular applications.

The biocompatibility of a new material for cardiovascular applications constituted by a poly(ether)urethane (PEtU) and a silicone [polydimethylsiloxane (PDMS)] was evaluated. The achieved material shows properties similar to both polyurethanes and silicones. The material was transformed into porous membranes by a spray-deposition technique. Since any material preparation and manufacturing procedure may introduce some toxicity, in vitro cytotoxicity screening tests were carried out. Human umbilical vein endothelial cells (HUVECs) and a mouse fibroblasts cell line (L929) were cultivated with extracts obtained from materials containing 10, 40 and 100% (w/w) of PDMS. The commercially available Estane 5714-F1 and Cardiothane 51 were used as controls. Extracts were incubated up to 72 hours with HUVECs and L929 cells. The cytotoxic effect was evaluated by light microscopy, cell viability (MTT reduction and neutral red uptake) and proliferation (5-bromo-2'-deoxyuridine incorporation) tests. In vivo studies were carried out using materials containing the same PDMS percentages as for in vitro experiments. The same commercial controls were used. Results obtained with cell culture studies agreed with those obtained in the in vivo experiments and showed that the material preparation and manufacturing procedure do not introduce any toxicity in the products at each PDMS concentration investigated.

Light microscopy evaluation of polyurethane vascular grafts porosity by Sudan Black B staining.

In small-diameter vascular grafts, the porosity of the internal surface plays an important role because it affects initial thrombus deposition and therefore the graft's patency. As well as many other studies reported in the literature we have carried out a study of the relationship between porosity and the manufacturing parameters of polyurethane (PU) grafts by standard scanning electron microscopy (SEM) analysis. However, SEM was not completely satisfactory for evaluating the 'sponge-like' uptake of water by the graft due to the unavoidable water loss and metal coating during preparation. In fact this preparation produces artefacts of the three-dimensional porous structure. To avoid this problem we investigated the possibility of observing the graft's internal surface through a stereomicroscope after it had absorbed water. We looked into a simple staining procedure which preferentially colours the PU graft fibres with respect to the void areas. After testing different kinds of stains, we eventually found that Sudan Black B, which usually stains for all kinds of lipid, turned out to be an excellent stain for the water-loaded PU grafts when diluted with ethanol. This staining procedure, coupled with a computerized image analysis system, allowed us to evaluate the degree of void and average void size of the graft internal surface and to correlate these data with graft density and manufacturing parameters.

The gut origin septic states in blunt multiple trauma (ISS = 40) in the ICU.

The association between support elements (ventilator days = Vd, enteral protein = EnP, number of antibiotics per day = AB/d) and the magnitude of the septic state (SSS) and its bacteriologic manifestations (bacti. log) in 66 patients with blunt multiple trauma (mean HTI-ISS = 40) over 1649 days have been studied retrospectively. SSS is measured by summing the standard deviation units of change in the septic direction for the 16 measurements taken every day in the intensive care unit. Increasing Vd is tightly associated with an increasing SSS (r = +0.52), after day 10 an increasing bacti. log (r = +0.21 to +0.32), and an increasing AB/d (r = +0.26) (all p less than 0.001, N = 1615 - 1626). The independent variables that best predicted Vd were delayed operations (DORS), day of rising EnP, and total positive blood cultures (TPC) (adj. R sq. = 0.84, F = 104, dF = 3/59). An increasing AB/d was associated with an increasing SSS (r = +0.38), increasing Vd (r = +0.26), and an increased bacti. log (r = +0.14 to +0.18) (all p less than 0.001, N = 1615). Only an increased EnP was consistently associated with a reduced SSS (r = -0.38) and a reduction in bacti. log (r = -0.10 to -0.21) (all p less than 0.001, N = 1626-1636). The independent variables Vd, EnP, AB/d, and TPC best predicted SSS for all surviving patients (adj. R sq. = 0.42, F = 268, dF = 4/1496). The patients who died of sepsis were not different in terms of bacti. log from those with equal Vd but were distinguished by zero EnP, high AB/d, and persistent ventilatory support. In conclusion, DORS is tightly associated with increased Vd, SSS, AB/d, and zero EnP. If Vd exceeds 10, there is an increasing bacti. log and evidence of infection probably from the gut. This responds only to increased EnP and not to AB/d. Death due to sepsis is not associated with increased bacti. log but with zero EnP and high AB/d and their consequences.