Sub-micron texturing for reducing platelet adhesion to polyurethane biomaterials.

Platelet adhesion is a key event in thrombus development on blood-contacting medical devices. It has been demonstrated that changes to the chemistry of a material surface can reduce platelet adhesion. In this work, it is hypothesized that sub-micron surface textures may also reduce adhesion via a decrease in the surface area of material with which platelets can make contact, and hence a decreased probability of interaction with adhesive ligands. A polyether(urethane urea) was textured with two different sizes of sub-micron pillars using a replication molding technique that did not alter the material surface chemistry. Adhesion of platelets was assessed in a physiologically relevant shear stress range of 0-67 dyn/cm2 using a rotating disk system. Platelets were immunofluorescently labeled and adhesion was compared on smooth and textured samples. Platelet adhesion was greatest at low shear stress ranging from 0 to 5 dyn/cm2, and sub-micron textures were observed to reduce platelet adhesion in this range. Additionally, non-adherent platelets did not demonstrate large-scale activation after exposure to textured samples. We conclude that surface textures with sub-platelet dimensions may reduce platelet adhesion from plasma to polyether(urethane urea) at low shear stress.

Short-term in vivo studies of surface thrombosis in a left ventricular assist system.

Thrombosis continues to be a major adverse and at times fatal event in patients with left ventricular assist systems (LVAS). To assess acute thrombosis in an LVAS, multiscale analysis of surface thrombosis was performed on LVAS blood sacs retrieved after implantation in seven calves for 3 days. Two study groups were evaluated: One group was given heparin and warfarin sodium throughout the study; the second received no postoperative anticoagulation. On explantation, the blood sacs were examined for macroscopic thrombi; microscale thrombosis was assessed with the use of scanning electron microscopy. Macroscopic thrombi about 1 mm in diameter were seen in all sacs from both groups. Although macroscopic thrombi occurred in all sac regions, scanning electron microscopy revealed differences in microscale topography between the port regions and the other sac regions. The primary structure was spherical particles approximately 400 nm in diameter, found to occur at a lower density in the ports. In contrast, the highest densities of proteinaceous rough topography and fibrillar structures consistent with fibrin clot were seen in the port regions. The density distribution of these structures was different in the eight sac regions, and anticoagulation therapy appeared to have no effect on surface thrombosis in these short-term LVAS implants.

Development of novel submicron textured polyether(urethane urea) for decreasing platelet adhesion.

Ventricular assist devices have proven to be a useful clinical option for providing circulatory support as a bridge to transplantation and a mode of destination therapy. Thromboembolism is prevented by designing devices that use blood interfaces that either encourage biological material deposition and strong adhesion, or discourage deposition via surface chemistry, surface finish, and fluid flow fields. Minimum continuous or periodic wall shear forces and maximum time at reduced shear are important, and sometimes difficult-to-satisfy, design constraints. We present an approach to reducing platelet adhesion via surface topography, reducing surface area for platelet-material interaction. Large areas of polyether(urethane urea) were textured with two different sizes of ordered pillar arrays via two-stage replication molding without affecting surface chemistry. Pillars had subplatelet dimensions designed to reduce the surface area a platelet may contact. Platelet adhesion was assessed in a physiologically relevant shear stress range from 0-10 dyn/cm2 using a rotating disk and compared to smooth control. Adhesion was highest from 0-5 dyn/cm2. Surface texturing reduced platelet adhesion without increasing platelet activation in bulk suspension. This study demonstrates that material surface texture is an additional variable that may be used to reduce platelet adhesion under low shear stresses potentially reducing thromboembolism.

Multiscale analysis of surface thrombosis in vivo in a left ventricular assist system.

Thrombosis limits the success of ventricular assist devices as the demand for alternatives to heart transplants is increasing. This study mapped the occurrence of thrombosis in a left ventricular assist system (LVAS) to better understand the biologic response to these devices. Nine calves divided into two groups were implanted with LVAS for 28 to 30 days. One group was anticoagulated, whereas the second group received no long-term anticoagulation. The blood-contacting poly(urethane urea) surfaces of blood sacs in the LVAS were examined for macroscopic thrombi upon retrieval. The sac was partitioned into eight sections and imaged for thrombi by scanning electron microscopy. No difference in thrombosis was observed macroscopically between the groups. Anticoagulation appeared to result in reduction of platelet-like structures, but the presence of fibrin-like structures remained similar between groups. Regional differences correlating with high and low shear stress regions were observed. At the macroscale, fewer thrombi were recorded in the high shear stress ports. At the microscale, features resembling fibrin were observed primarily in the ports and platelet-like features were common in lower shear stress regions. These variations in thrombosis with anticoagulation and location are likely due to varied fluid dynamics within the LVAS blood sac.

Durability testing of a completely implantable electric total artificial heart.

In vitro durability testing was conducted on the Penn State/3M electric total artificial heart (ETAH) to determine device durability and to evaluate device failures. A specialized mock circulatory loop was developed for this testing. Customized software continuously acquired data during the test period, and failures were analyzed using FMEA (failure modes and effects analysis) and FMECA (failure modes, effects, and criticality analysis) principles. Redesigns were implemented when appropriate. Reliability growth principles were then applied to calculate the 1 and 2 year reliability. The 1 and 2 year reliability of the Penn State/3M ETAH was shown to be 96.1% and 59.9%, respectively, at 80% confidence.

Precise quantification of pressure flow waveforms of a pulsatile ventricular assist device.

Unreliable quantification of flow pulsatility has hampered many efforts to assess the importance of pulsatile perfusion. Generation of pulsatile flow depends upon an energy gradient. It is necessary to quantify pressure flow waveforms in terms of hemodynamic energy levels to make a valid comparison between perfusion modes during chronic support. The objective of this study was to quantify pressure flow waveforms in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) levels in an adult mock loop using a pulsatile ventricle assist system (VAD). A 70 cc Pierce-Donachy pneumatic pulsatile VAD was used with a Penn State adult mock loop. The pump flow rate was kept constant at 5 L/min with pump rates of 70 and 80 bpm and mean aortic pressures (MAP) of 80, 90, and 100 mm Hg, respectively. Pump flows were adjusted by varying the systolic pressure, systolic duration, and the diastolic vacuum of the pneumatic drive unit. The aortic pressure was adjusted by varying the systemic resistance of the mock loop EEP (mm Hg) = (integral of fpdf)/(integral of fdt) SHE (ergs/cm3) = 1,332 [((integral of fpdt)/(integral of fdt))--MAP] were calculated at each experimental stage. The difference between the EEP and the MAP is the extra energy generated by this device. This difference is approximately 10% in a normal human heart. The EEP levels were 88.3 +/- 0.9 mm Hg, 98.1 +/- 1.3 mm Hg, and 107.4 +/- 1.0 mm Hg with a pump rate of 70 bpm and an aortic pressure of 80 mm Hg, 90 mm Hg, and 100 mm Hg, respectively. Surplus hemodynamic energy in terms of ergs/cm3 was 11,039 +/- 1,236 ergs/cm3, 10,839 +/- 1,659 ergs/cm3, and 9,857 +/- 1,289 ergs/cm3, respectively. The percentage change from the mean aortic pressure to EEP was 10.4 +/- 1.2%, 9.0 +/- 1.4%, and 7.4 +/- 1.0% at the same experimental stages. Similar results were obtained when the pump rate was changed from 70 bpm to 80 bpm. The EEP and SHE formulas are adequate to quantify different levels of pulsatility for direct and meaningful comparisons. This particular pulsatile VAD system produces near physiologic hemodynamic energy levels at each experimental stage.

Low permeability biomedical polyurethane nanocomposites.

In this article we describe our continuing research on a novel nanocomposite approach for reducing gas permeability through biomedical polyurethane membranes. Nanocomposites were prepared using commercially available poly(urethane urea)s (PUU) and two organically modified layered silicates (OLS). Wide-angle X-ray diffraction experiments showed that the silicate layer spacing in the nanocomposites increased significantly compared with the neat OLS, signifying the formation of intercalated PUU/OLS structures. The nanocomposite materials exhibit increased modulus with increasing OLS content, while maintaining polymer strength and ductility. Water vapor permeability was reduced by about fivefold at the highest OLS contents, as a result of PUU/inorganic composite formation.

Bioengineering and Bioinformatics Summer Institutes: meeting modern challenges in undergraduate summer research.

Summer undergraduate research programs in science and engineering facilitate research progress for faculty and provide a close-ended research experience for students, which can prepare them for careers in industry, medicine, and academia. However, ensuring these outcomes is a challenge when the students arrive ill-prepared for substantive research or if projects are ill-defined or impractical for a typical 10-wk summer. We describe how the new Bioengineering and Bioinformatics Summer Institutes (BBSI), developed in response to a call for proposals by the National Institutes of Health (NIH) and the National Science Foundation (NSF), provide an impetus for the enhancement of traditional undergraduate research experiences with intense didactic training in particular skills and technologies. Such didactic components provide highly focused and qualified students for summer research with the goal of ensuring increased student satisfaction with research and mentor satisfaction with student productivity. As an example, we focus on our experiences with the Penn State Biomaterials and Bionanotechnology Summer Institute (PSU-BBSI), which trains undergraduates in core technologies in surface characterization, computational modeling, cell biology, and fabrication to prepare them for student-centered research projects in the role of materials in guiding cell biology.