Influence of Polymer Stiffness and Geometric Design on Fluid Mechanics in Tissue-Engineered Pulmonary Valve Scaffolds.

There is still much unknown about the fluid mechanical response to cardiac valve scaffolds, even as their implementation in the clinic is on the horizon. Specifically, while degradable polymer valve scaffolds are currently being tested in the pulmonary valve position, their material and mechanical properties have not been fully elucidated. Optimizing these properties are important determinants not only of acute function, but long-term remodeling prospects. This study aimed to characterize fluid profiles downstream of electrospun valve scaffolds under dynamic pulmonary conditions. Valve scaffold design was changed by either blending poly(carbonate urethane) urea (PCUU) with poly(ε-caprolactone) (PCL) to modulate material stiffness or by changing the geometric design of the valve scaffolds. Specifically, two designs were utilized: one modeled after a clinically used bioprosthetic valve design (termed Mk1 design), and another using a geometrically "optimized" design (termed Mk2) based on anatomical data. Particle image velocimetry results showed that material stiffness only had a mild impact on fluid mechanics, measured by velocity magnitude, vorticity, viscous shear stress, Reynolds shear stress, and turbulent kinetic energy. However, comparing the two geometric designs yielded a much greater impact, with the Mk2 valve groups containing the highest PCUU/PCL ratio demonstrating the overall best performance. This report highlights the easily manipulable design features of polymeric valve scaffolds and demonstrates their relative significance for valve function.

Cardiac valve scaffold design: Implications of material properties and geometric configuration on performance and mechanics.

Development of tissue engineered scaffolds for cardiac valve replacement is nearing clinical translation. While much work has been done to characterize mechanical behavior of native and bioprosthetic valves, and incorporate those data into models improving valve design, similar work for degradable valve scaffolds is lacking. This is particularly important given the implications mechanics have on short-term survival and long-term remodeling. As such, this study aimed to characterize spatially-resolved strain profiles on the leaflets of degradable polymeric valve scaffolds, manipulating common design features such as material stiffness by blending poly(carbonate urethane)urea with stiffer polymers, and geometric configuration, modeled after either a clinically-used valve design (Mk1 design) or an anatomically "optimized" design (Mk2 design). It was shown that material stiffness plays a significant role in overall valve performance, with the stiffest valve groups showing asymmetric and incomplete opening during systole. However, the geometric configuration had a significantly greater effect on valve performance as well as strain magnitude and distribution. Major findings in the strain maps included systolic strains having overall higher strain magnitudes than diastole, and peak radial-direction strain concentrations in the base region of Mk1 valves during systole, with a significant mitigation of radial strain in Mk2 valves. The high tunability of tissue engineered scaffolds is a great advantage for valve design, and the results reported here indicate that design parameters have significant and unequal impact on valve performance and mechanics.

Biodegradable polyurethane scaffolds in regenerative medicine: Clinical translation review.

Early explorations of tissue engineering and regenerative medicine concepts commonly utilized simple polyesters such as polyglycolide, polylactide, and their copolymers as scaffolds. These biomaterials were deemed clinically acceptable, readily accessible, and provided processability and a generally known biological response. With experience and refinement of approaches, greater control of material properties and integrated bioactivity has received emphasis and a broadened palette of synthetic biomaterials has been employed. Biodegradable polyurethanes (PUs) have emerged as an attractive option for synthetic scaffolds in a variety of tissue applications because of their flexibility in molecular design and ability to fulfill mechanical property objectives, particularly in soft tissue applications. Biodegradable PUs are highly customizable based on their composition and processability to impart tailored mechanical and degradation behavior. Additionally, bioactive agents can be readily incorporated into these scaffolds to drive a desired biological response. Enthusiasm for biodegradable PU scaffolds has soared in recent years, leading to rapid growth in the literature documenting novel PU chemistries, scaffold designs, mechanical properties, and aspects of biocompatibility. Despite the enthusiasm in the field, there are still few examples of biodegradable PU scaffolds that have achieved regulatory approval and routine clinical use. However, there is a growing literature where biodegradable PU scaffolds are being specifically developed for a wide range of pathologies and where relevant pre-clinical models are being employed. The purpose of this review is first to highlight examples of clinically used biodegradable PU scaffolds, and then to summarize the growing body of reports on pre-clinical applications of biodegradable PU scaffolds.

Continuous Microfiber Wire Mandrel-Less Biofabrication for Soft Tissue Engineering Applications.

Suture materials are the most common bioimplants in surgical and clinical practice, playing a crucial role in wound healing and tendon and ligament repair. Despite the assortment available on the market, sutures are still affected by significant disadvantages, including failure in mimicking the mechanical properties of the tissue, excessive fibrosis, and inflammation. This study introduces a mandrel-less electrodeposition apparatus to fabricate continuous microfiber wires of indefinite length. The mandrel-less biofabrication produces wires, potentially used as medical fibers, with different microfiber bundles, that imitate the hierarchical organization of native tissues, and tailored mechanical properties. Microfiber wire morphology and mechanical properties are characterized by scanning electron microscopy, digital image processing, and uniaxial tensile test. Wires are tested in vitro on monocyte/macrophage stimulation and in vivo on a rat surgical wound model. The wires produced by mandrel-less deposition show an increased M2 macrophage phenotype in vitro. The in vivo assessment demonstrates that microfiber wires, compared to the medical fibers currently used, reduce pro-inflammatory macrophage response and preserve their mechanical properties after 30 days of use. These results make this microfiber wire an ideal candidate as a suture material for soft tissue surgery, suggesting a crucial role of microarchitecture in more favorable host response.

Cytocompatibility and mechanical properties of surgical sealants for cardiovascular applications.

OBJECTIVES: The present study compared physical, mechanical, and biologic characteristics of 4 clinically available surgical sealants for cardiovascular repair. METHODS: BioGlue (Cryolife Inc, Kennesaw, Ga), PreveLeak (Mallinckrodt Pharmaceuticals, St Louis, Mo), Tridyne VS (BD, Franklin Lakes, NJ), and Coseal (Baxter Healthcare Corporation, Westlake Village, Calif) were compared for the following properties: hydrated swelling, cytocompatibility, burst strength, biaxial stretching (elasticity), and in vitro degradation. RESULTS: Sealants showed a wide range of swelling upon hydration. By gravimetric and volumetric measurement, swelling was greatest for Coseal followed by Tridyne VS, BioGlue, and PreveLeak. Tridyne VS was the most cytocompatible based on Alamar Blue assay results, supporting 85% cell survival compared with 36% to 39% survival with the other sealants. All sealants withstood pressure above mean arterial pressure (70-110 mm Hg) and physiologic systolic blood pressure (90-140 mm Hg) in an ex vivo arterial flow burst model; lowest peak pressure at failure was PreveLeak at 235 ± 48 mm Hg, and highest peak pressure at failure was BioGlue at 596 ± 72 mm Hg. Biaxial tensile testing showed no differences in elasticity between ex vivo porcine aorta and carotid arteries and Tridyne VS or Coseal, and BioGlue and PreveLeak were significantly stiffer. In vitro degradation time for Coseal was 6 days and 21 days for Tridyne VS. No degradation was observed in BioGlue or PreveLeak for 30 days. CONCLUSIONS: Although all sealants withstood supraphysiologic arterial pressure, there were differences in characteristics that may be important in clinical outcome. Coseal degradation time was short compared with other sealants, whereas BioGlue and PreveLeak showed a significant compliance mismatch with native porcine carotid artery. Tridyne VS was significantly more cytocompatible than the other 3 sealants.

In vivo functional assessment of a novel degradable metal and elastomeric scaffold-based tissue engineered heart valve.

OBJECTIVE: Ideal heart valve solutions aim to provide thrombosis-free durability. A scaffold-based polycarbonate urethane urea tissue-engineered heart valve designed to mimic native valve microstructure and function was used. This study examined the acute in vivo function of a stented tissue-engineered heart valve in a porcine model. METHODS: Trileaflet valves were fabricated by electrospinning polycarbonate urethane urea using double component fiber deposition. The tissue-engineered heart valve was mounted on an AZ31 magnesium alloy biodegradable stent frame. Five 80-kg Yorkshire pigs underwent open tissue-engineered heart valve implantation on cardiopulmonary bypass in the pulmonary position. Tissue-engineered heart valve function was echocardiographically evaluated immediately postimplant and at planned study end points at 1, 4, 8, and 12 hours. Explanted valves underwent biaxial mechanical testing and scanning electron microscopy for ultrastructural analysis and thrombosis detection. RESULTS: All 5 animals underwent successful valve implantation. All were weaned from cardiopulmonary bypass, closed, and recovered until harvest study end point except 1 animal that was found to have congenital tricuspid valve dysplasia and that was euthanized postimplant. All 5 cases revealed postcardiopulmonary bypass normal leaflet function, no regurgitation, and an average peak velocity of 2 m/s, unchanged at end point. All tissue-engineered heart valve leaflets retained microstructural architecture with no platelet activation or thrombosis by scanning electron microscopy. There was microscopic evidence of fibrin deposition on 2 of 5 stent frames, not on the tissue-engineered heart valve. Biaxial stress examination revealed retained postimplant mechanics of tissue-engineered heart valve fibers without functional or ultrastructural degradation. CONCLUSIONS: A biodegradable elastomeric heart valve scaffold for in situ tissue-engineered leaflet replacement is acutely functional and devoid of leaflet microthrombosis.

Visualization and analysis of biomaterial-centered thrombus formation within a defined crevice under flow.

The blood flow pathway within a device, together with the biomaterial surfaces and status of the patient's blood, are well-recognized factors in the development of thrombotic deposition and subsequent embolization. Blood flow patterns are of particular concern for devices such as blood pumps (i.e. ventricular assist devices, VADs) where shearing forces can be high, volumes are relatively large, and the flow fields can be complex. However, few studies have examined the effect of geometric irregularities on thrombus formation on clinically relevant opaque materials under flow. The objective of this study was to quantify human platelet deposition onto Ti6Al4V alloys, as well as positive and negative control surfaces, in the region of defined crevices (∼50-150 µm in width) that might be encountered in many VADs or other cardiovascular devices. To achieve this, reconstituted fresh human blood with hemoglobin-depleted red blood cells (to achieve optical clarity while maintaining relevant rheology), long working optics, and a custom designed parallel plate flow chamber were employed. The results showed that the least amount of platelet deposition occurred in the largest crevice size examined, which was counterintuitive. The greatest levels of deposition occurred in the 90 µm and 53 µm crevices at the lower wall shear rate. The results suggest that while crevices may be unavoidable in device manufacturing, the crevice size might be tailored, depending on the flow conditions, to reduce the risk of thromboembolic events. Further, these data might be used to improve the accuracy of predictive models of thrombotic deposition in cardiovascular devices to help optimize the blood flow path and reduce device thrombogenicity.