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An implantable hemofilter for the treatment of kidney failure depends critically on the transport characteristics of the membrane and the biocompatibility of the membrane, cartridge, and blood conduits. A novel membrane with slit-shaped pores optimizes the trade-off between permeability and selectivity, enabling implanted therapy. Sustained (3-8) day function of an implanted parallel-plate hemofilter with minimal anticoagulation was achieved by considering biocompatibility at the subnanometer scale of chemical interactions and the millimeter scale of blood fluid dynamics. A total of 400 nm-thick polysilicon flat sheet membranes with 5-8 nm × 2 micron slit-shaped pores were surface-modified with polyethylene glycol. Hemofilter cartridge geometries were refined based on computational fluid dynamics models of blood flow. In an uncontrolled pilot study, silicon filters were implanted in six class A dogs. Cartridges were connected to the cardiovascular system by anastamoses to the aorta and inferior vena cava and filtrate was drained to collection pouches positioned in the peritoneum. Pain medicine and acetylsalicylic acid were administered twice daily until the hemofilters were harvested on postoperative days 3 (n = 2), 4 (n = 2), 5 (n = 1), and 8 (n = 1). No hemofilters were thrombosed. Animals treated for 5 and 8 days had microscopic fractures in the silicon nanopore membranes and 20-50 ml of transudative (albumin sieving coefficient θalb ~ 0.5 - 0.7) fluid in the collection pouches at the time of explant. Shorter experimental durations (3-4 days) resulted in filtration volumes similar to predictions based on mean arterial pressures and membrane hydraulic permeability and (θalb ~ 0.2 - 0.3), similar to preimplantation measurements. In conclusion, a detailed mechanistic and materials science attention to blood-material interactions allows implanted hemofilters to resist thrombosis. Additional testing is needed to determine optimal membrane characteristics and identify limiting factors in long-term implantation.
Silicon nanopore membranes (SNMs) with compact geometry and uniform pore size distribution have demonstrated a remarkable capacity for hemofiltration. These advantages could potentially be used for hemodialysis. Here, we present an initial evaluation of the SNM's mechanical robustness, diffusive clearance, and hemocompatibility in a parallel plate configuration. Mechanical robustness of the SNM was demonstrated by exposing membranes to high flows (200 ml/min) and pressures (1,448 mm Hg). Diffusive clearance was performed in an albumin solution and whole blood with blood and dialysate flow rates of 25 ml/min. Hemocompatibility was evaluated using scanning electron microscopy and immunohistochemistry after 4 hours in an extracorporeal porcine model. The pressure drop across the flow cell was 4.6 mm Hg at 200 ml/min. Mechanical testing showed that SNM could withstand up to 775.7 mm Hg without fracture. Urea clearance did not show an appreciable decline in blood versus albumin solution. Extracorporeal studies showed blood was successfully driven via the arterial-venous pressure differential without thrombus formation. Bare silicon showed increased cell adhesion with a 4.1-fold increase and 1.8-fold increase over polyethylene glycol (PEG)-coated surfaces for tissue plasminogen factor (t-PA) and platelet adhesion (CD41), respectively. These initial results warrant further design and development of a fully scaled SNM-based parallel plate dialyzer for renal replacement therapy.
Polypropylene meshes, originally introduced for hernia repair, are presently utilized in several anatomical sites. Several million are implanted annually worldwide. Depending on the device, up to 10% will be excised to treat complications. The excised meshes can provide material to study the complications, however, they have remained underutilized over the last decades and the mechanisms of complications continue to be incompletely understood. The fundamental question as to whether polypropylene degrades in vivo is still debated. We have examined 164 excised meshes using conventional microscopy to search for features of polypropylene degradation. Four specimens were also examined by transmission electron microscopy. The degraded material, detected by its ability to absorb dyes in the degradation nanopores, formed a continuous layer at the surface of the mesh fibers. It retained birefringence, inclusions of non-degraded polypropylene, and showed ability to meld with the non-degraded fiber core when heated by the surgical cautery. Several features indicated that the degradation layer formed in vivo: inflammatory cells trapped within fissures, melting caused by cautery of excision surgery, and gradual but progressive growth of the degradation layer while in the body. Cracking of the degraded material indicated a contribution to clinically important mesh stiffening and deformation. Chemical products of degradation need to be analyzed and studied for their role in the mesh-body interactions. The described methods can also be used to study degradation of other materials. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 237-248, 2017.
© 2015 Wiley Periodicals, Inc.
UNLABELLED - The major goal of this study was to create easy-to-use, reusable substrates capable of storing any peptides or bioactive molecules for a desired period of time until cells uptake them without the need for bioactive molecule or peptide-specific techniques. Nanopore arrays of uniform size and distribution were machined into fused silica substrates using femtosecond laser ablation and loaded with peptides by simple adsorption. The nanopore substrates were validated by examining the effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) loaded nanopores on macrophage phagocytosis and intracellular production of reactive oxygen species (ROS) with and without the pro-inflammatory lipopolysaccharide (LPS). Our results demonstrated that nanopores were generated in a uniform array fashion. Ac-SDKP peptides were stably stored in nanopores and internalized by macrophages. Significant reductions in ROS production and phagocytosis in macrophages were observed over control substrates, even in combination with LPS stimulation, indicating that loading Ac-SDKP peptides in pores significantly improved the anti-inflammatory effects.
FROM THE CLINICAL EDITOR - This team of scientists intended to create easy-to-use, reusable substrates for storing peptides or bioactive molecules for a desired period of time before cellular uptake occurs, and without the need for bioactive molecule or peptide-specific techniques. They demonstrate the successful generation of nanopores in a uniform array that stably stores Ac-SDKP peptides in the nanopores. When peptides were internalized by macrophages, significant reductions in ROS production and phagocytosis were observed, indicating improved anti-inflammatory effects.
We present a method for direct three-dimensional (3D) patterning of porous nanomaterials through the application of a premastered and reusable gray-scale stamp. Four classes of 3D nanostructures are demonstrated for the first time in porous media: gradient profiles, digital patterns, curves and lens shapes, and sharp features including v-grooves, nano-pits, and 'cookie-cutter' particles. Further, we demonstrate this technique enables morphological tuning and direct tailoring of nanomaterial properties, including porosity, average pore size, dielectric constant, and plasmonic response. This work opens a rapid and low-cost route for fabricating novel nanostructures and devices utilizing porous nanomaterials, with promising applications spanning diffractive and plasmonic sensing, holography, micro- and transformation optics, and drug delivery and imaging.
Time-dependent laser reflectometry measurements are presented as a means to rigorously characterize analyte diffusion dynamics of small molecules from mesoporous silicon (PSi) films for drug delivery and membrane physics applications. Calculations based on inclusion of a spatially and temporally dependent solute concentration profile in a one-dimensional Fickian diffusion flow model are performed to determine the diffusion coefficients for the selected prototypical polar species, sucrose (340 Da), exiting from PSi films. The diffusion properties of the molecules depend on both PSi pore size and film thickness. For films with average pore diameters between 10-30 nm and film thicknesses between 300-900 nm, the sucrose diffusion coefficient can be tuned between approximately 100 and 550 μm2/s. Extensions of the real-time measurement and modeling approach for determining the diffusivity of small molecules that strongly interact with and corrode the internal surfaces of PSi films are also discussed.
Silicon nanopore membranes (SNM) with monodisperse pore size distributions have potential applications in bioartificial kidneys. A protein resistant thin film coating on the SNM is required to minimize biofouling and, hence, enhance the performance efficiency of SNM. In this work, a zwitterionic polymer, poly(sulfobetaine methacrylate) (polySBMA), was used to coat silicon and SNM substrates via a surface initiated atom transfer radical polymerization method. The polySBMA-coated surfaces were characterized using contact angle goniometry, X-ray photoelectron spectroscopy (XPS), ellipsometry and scanning electron microscopy (SEM). Resistance of the coatings to protein fouling was examined by measurement of fibrinogen adsorption from fibrinogen solution and human plasma on coated silicon surfaces. Results showed that the polySBMA coating suppresses non-specific adsorption of fibrinogen. The protein-repellent property of polySBMA thin film coating is comparable to that of PEG-based coatings. Analysis of the surfaces by XPS indicated that the films remained stable when stored under physiologic conditions over a 4-week period.