ABSTRACT
Polytetrafluoroethylene (PTFE) and expanded PTFE (ePTFE) are ideal for various applications. Because PTFE does not flow, even when heated above its melting point, PTFE components are fabricated using a process called paste extrusion. This process entails blending PTFE powder particles with a lubricant to form PTFE paste, which is subsequently preformed, extruded, expanded (in the case of ePTFE), and sintered. In this study, ethanol was proposed as an alternative green lubricant for PTFE processing. Not only is ethanol benign and biofriendly, it provides excellent wettability and processing benefits. Using ethanol as a lubricant, the shear viscosity of PTFE paste and its flow behavior during paste extrusion were investigated. Frequency sweeps using a parallel-plate rheometer were performed on PTFE paste samples and various grits of sandpaper were used to reduce wall slip of PTFE paste. A viscosity model was generated and a multiphysics software was used to simulate PTFE paste extrusion. The simulated extrusion pressure was compared to experimental data of actual paste extrusion. Flow visualization experiments using colored PTFE layers were conducted to reveal the flow profile of the PTFE paste. The morphology of the expanded ePTFE tubes was examined using scanning electron microscopy and the effect of expansion ratio on ePTFE morphology was quantified.
ABSTRACT
Magnetic levitation (MagLev) is a promising technology for density-based analysis and manipulation of diamagnetic objects of various physical forms. However, one major drawback is that MagLev can be performed only along the central axis (one-dimensional MagLev), thereby leading to (i) no knowledge about the magnetic field in regions other than the axial region, (ii) inability to handle objects of similar densities, because they are aggregated in the axial region, and (iii) objects that can be manipulated (e.g., separated or assembled) in only one single direction, that is, the axial direction. This work explores a novel approach called "axial-circular MagLev" to expand the operational space from one dimension to three dimensions, enabling substances to be stably levitated in both the axial and circular regions. Without noticeably sacrificing the total density measurement range, the highest sensitivity of the axial-circular MagLev device can be adjusted up to 1.5 × 104 mm/(g/cm3), approximately 115× better than that of the standard MagLev of two square magnets. Being able to fully utilize the operational space gives this approach greater maneuverability, as the three-dimensional self-assembly of controllable ring-shaped structures is demonstrated. Full space utilization extends the applicability of MagLev to bioengineering, pharmaceuticals, and advanced manufacturing.
Subject(s)
Formaldehyde/analysis , Polymers/analysis , Polymers/chemistry , Glass/analysis , Magnetic FieldsABSTRACT
Cardiovascular diseases plague human health because of the lack of transplantable small-diameter blood vessel (SDBV) grafts. Although expanded polytetrafluoroethylene (ePTFE) has the potential to be used as a biocompatible material for SDBV grafts, long-term patency is still the biggest challenge. As discussed in this paper, by virtue of a novel material formulation and a new and benign alcohol/water lubricating agent, biofunctionalized ePTFE blood vessel grafts aimed at providing long-term patency were fabricated. Compared to the most prevalent modification of PTFE, namely surface treatment, this method realized bulk treatment, which could guarantee homogeneous and long-lasting performance throughout PTFE products. These blood vessel grafts included embedded functional biomolecules, such as arginylglycylaspartic acid, heparin, and selenocystamine, using water as a solvent in paste extrusion and in the expansion of ePTFE. Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and scanning electron microscope results confirmed the existence of these targeting biomolecules in the as-fabricated ePTFE blood vessel grafts. Meanwhile, the greatly improved biological functions of the grafts were demonstrated via live and dead assays, cell morphology, CD31 staining, nitric oxide (NO) release, and anticoagulation tests. This novel and benign material formulation and fabrication method provides an opportunity to produce multibiofunctional ePTFE blood vessel grafts in a single step, thus yielding a potent product with significant commercial and clinical potential.
Subject(s)
Blood Vessel Prosthesis , Polytetrafluoroethylene , Biocompatible Materials , Heparin , HumansABSTRACT
During the regeneration of tissues and organs, growth factors (GFs) play a vital role by affecting cell behavior. However, because of the low half-life time and quick degradation of GFs, their stimulations on cells are relatively short and discontinuous. In this study, a releasing scaffold platform, consisting of polycaprolactone (PCL) nanofibers and vascular endothelial growth factor (VEGF)-encapsulated gelatin particles, was developed to extend the influence of GFs on mesenchymal stem cells (MSCs) and endothelial cells (ECs). The results showed that this kind of scaffold can direct the differentiation of MSCs to ECs and maintain the stability of the tubular structure, an indicator of the angiogenesis ability of ECs, for an extended period of time. Therefore, the results suggest the potential application of PCL/VEGF-encapsulated gelatin particles (PCL/VGPs) as a growth factor (GF)-releasing scaffold platform in vascular tissue engineering.
Subject(s)
Cell Differentiation , Gelatin/chemistry , Mesenchymal Stem Cells/cytology , Polyesters/chemistry , Tissue Scaffolds/chemistry , Vascular Endothelial Growth Factor A/pharmacology , Cells, Cultured , Drug Liberation , Endothelial Cells/cytology , Endothelial Cells/drug effects , Humans , Mesenchymal Stem Cells/drug effects , Nanofibers/chemistry , Nanoparticles/chemistry , Neovascularization, Physiologic , Vascular Endothelial Growth Factor A/chemistryABSTRACT
Mimicking the mechanical properties of native tissues is a critical criterion for an ideal tissue engineering scaffold. However, most biodegradable synthetic materials, including polyester-based polyurethanes (PUs), consist of rigid polyester chains and have high crystallinity. They typically lack the elasticity of most human tissues. In this study, a new type of biodegradable PU with excellent elasticity was synthesized based on the controlled crosslinking of poly(ester ether) triblock copolymer diols and polycaprolactone (PCL) triols using urethane linkages. Three-dimensional (3D) porous scaffolds with a defined geometry, tunable microstructures, and adjustable mechanical properties were synthesized in situ using an isocyanate-ended copolymer, a tri-armed PCL, and a chain extender. The mechanical properties of the scaffolds can be easily tuned by changing the ratio of reactants, varying the solution concentration, or using a porogen. Notably, all of these scaffolds, although mostly made of rigid PCL chains, showed remarkable elasticity and cyclical properties. With an optimized molecular design, a maximum recovery rate of 99.8% was achieved. This was because the copolymer provided molecular flexibility while the long chain crosslinking of PCL triol hindered crystallization, thus making the PU behave like an amorphous elastic material. Moreover, the in vitro cell culture of 3T3 fibroblasts and MG63 osteoblast-like cells confirmed the biocompatibility of these PU scaffolds and revealed that scaffolds with different stiffnesses can stimulate the proliferation of different types of cells. All of these attributes make PU scaffolds extremely suitable for the regeneration of tissues that experience dynamic loading.
ABSTRACT
Cardiovascular diseases (CVDs) are the number one cause of mortality among non-communicable diseases worldwide. Expanded polytetrafluoroethylene (ePTFE) is a widely used material for making artificial vascular grafts to treat CVDs; however, its application in small-diameter vascular grafts is limited by the issues of thrombosis formation and intimal hyperplasia. This paper presents a novel approach that integrates a hydrogel layer on the lumen of ePTFE vascular grafts through mechanical interlocking to efficiently facilitate endothelialization and alleviate thrombosis and restenosis problems. This study investigated how various gel synthesis variables, including N,N'-Methylenebisacrylamide (MBAA), sodium alginate, and calcium sulfate (CaSO4), influence the mechanical and rheological properties of P(AAm-co-NaAMPS)-alginate-xanthan hydrogels intended for vascular graft applications. The findings obtained can provide valuable guidance for crafting hydrogels suitable for artificial vascular graft fabrication. The increased sodium alginate content leads to increased equilibrium swelling ratios, greater viscosity in hydrogel precursor solutions, and reduced transparency. Adding more CaSO4 decreases the swelling ratio of a hydrogel system, which offsets the increased swelling ratio caused by alginate. Increased MBAA in the hydrogel system enhances both the shear modulus and Young's modulus while reducing the transparency of the hydrogel system and the pore size of freeze-dried samples. Overall, Hydrogel (6A12M) with 2.58 mg/mL CaSO4 was the optimal candidate for ePTFE-hydrogel vascular graft applications due to its smallest pore size, highest shear storage modulus and Young's modulus, smallest swelling ratio, and a desirable precursor solution viscosity that facilitates fabrication.
ABSTRACT
A three-dimensional structure consisting of poly(ε-caprolactone) (PCL) nanofibers covered by periodically spaced PCL crystal lamellae, a self-induced nanohybrid shish-kebab (SINSK) structure, was created using electrospinning followed by a self-induced crystallization. The resulting structure that resembles the nanotopography of natural collagen nanofibrils in the extracellular matrix (ECM) of human tissues could serve as a tissue engineering scaffold. The formation mechanism of the self-induced shish-kebab structure was investigated with real-time observation of the crystallization process. Electrospun polylactic acid (PLA)/PCL nanofibers were also employed as shish elements to study the effects of different shish materials. The results show that the geometric dimensions of the shish-kebabs are highly related to the initial concentration of PCL solution. The shish material played an important role in the creation of shish-kebab structure. Cell assays with NIH 3T3 ECACC fibroblasts suggest that the nanotopography of the nanofiber surface with kebab crystals that mimic collagen fibrils facilitated the cell attachment and spreading of 3T3 fibroblasts cells.
Subject(s)
Fibrillar Collagens/chemistry , Molecular Mimicry , Nanofibers/chemistry , Polyesters/chemistry , Fibrillar Collagens/chemical synthesis , Humans , Particle Size , Polyesters/chemical synthesis , Surface PropertiesABSTRACT
Cardiovascular diseases (CVDs) are the leading cause of death among all non-communicable diseases globally. Although expanded polytetrafluoroethylene (ePTFE) has been widely used for larger-diameter vascular graft transplantation, the persistent thrombus formation and intimal hyperplasia of small-diameter vascular grafts (SDVGs) made of ePTFE to treat severe CVDs remain the biggest challenges due to lack of biocompatibility and endothelium. In this study, bi-layered poly(acrylamide-co-2-Acrylamido-2-methyl-1-propanesulfonic acid sodium)-xanthan hydrogel-ePTFE (poly(AAm-co-NaAMPS)-xanthan hydrogel-ePTFE) vascular grafts capable of promoting endothelialization and prohibiting thrombosis were synthesized and fabricated. While the external ePTFE layer of the vascular grafts provided the mechanical stability, the inner hydrogel layer offered much-needed cytocompatibility, hemocompatibility, and endothelialization functions. The interface morphology between the inner hydrogel layer and the outer ePTFE layer was observed by scanning electron microscope (SEM), which revealed that the hydrogel was well attached to the porous ePTFE through mechanical interlocking. Among all the hydrogel compositions tested with cell culture using human umbilical vein endothelial cells (HUVECs), the hydrogel with the molar ratio of 40:60 (NaAMPS/AAm) composition (i.e., Hydrogel 40:60) exhibited the best endothelialization function, as it produced the largest endothelialization area that was three times more than of that of plain ePTFE on day 14, maintained the highest average cell viability, and had the best cell morphology. Hydrogel 40:60 also showed excellent hemocompatibility, prolonged activated partial thromboplastin time (aPTT), and good mechanical properties. Overall, bi-layered poly(AAm-co-NaAMPS)-xanthan hydrogel-ePTFE vascular grafts with the Hydrogel 40:60 composition could potentially solve the critical challenge of thrombus formation in vascular graft transplantation applications.
Subject(s)
Hydrogels , Thrombosis , Humans , Polytetrafluoroethylene , Human Umbilical Vein Endothelial CellsABSTRACT
Thermoplastic polyurethane (TPU) materials have shown promise in tissue engineering applications due to their mechanical properties and biocompatibility. However, the addition of nanoclays to TPU can further enhance its properties. In this study, the effects of nanoclays on the microstructure, mechanical behavior, cytocompatibility, and proliferation of TPU/nanoclay (TPUNC) composite scaffolds were comprehensively investigated. The dispersion morphology of nanoclays within the TPU matrix was examined using transmission electron microscopy (TEM). It was found that the nanoclays exhibited a well-dispersed and intercalated structure, which contributed to the improved mechanical properties of the TPUNC scaffolds. Mechanical testing revealed that the addition of nanoclays significantly enhanced the compressive strength and elastic resilience of the TPUNC scaffolds. Cell viability and proliferation assays were conducted using MG63 cells cultured on the TPUNC scaffolds. The incorporation of nanoclays did not adversely affect cell viability, as evidenced by the comparable cell numbers between nanoclay-filled and unfilled TPU scaffolds. The presence of nanoclays within the TPUNC scaffolds did not disrupt cell adhesion or proliferation. The incorporation of nanoclays improved the dispersion morphology, enhanced mechanical performance, and maintained excellent biocompatibility. These findings suggest that TPUNC composites have great potential for tissue engineering applications, providing a versatile and promising scaffold material for regenerative medicine.
ABSTRACT
Conventional solid injection molding (CIM) and microcellular injection molding (MIM) of a highly filled polycarbonate (PC) composite with glass fibers and carbon black were performed for molding ASTM tensile test bars and a box-shape part with variable wall thickness. A scanning electron microscope (SEM) was used to examine the microstructure at the fractured surface of the tensile test bar samples. The fine and uniform cellular structure suggests that the PC composite is a suitable material for foaming applications. Standard tensile tests showed that, while the ultimate strength and elongation at break were lower for the foamed test bars at 4.0-11.4% weight reduction, their specific Young's modulus was comparable to that of their solid counterparts. A melt flow and transition model was proposed to explain the unique, irregular "tiger-stripes" exhibited on the surface of solid test bars. Increasing the supercritical fluid (SCF) dosage and weight reduction of foamed samples resulted in swirl marks on the part surface, making the tiger-stripes less noticeable. Finally, it was found that an injection pressure reduction of 25.8% could be achieved with MIM for molding a complex box-shaped part in a consistent and reliable fashion.
ABSTRACT
This paper explored the injection foaming process of in situ fibrillation reinforced polypropylene composites. Using polypropylene (PP) as the continuous phase, polytetrafluoroethylene (PTFE) as the dispersed phase, multi-wall carbon nanotubes (MWCNTs) as the conductive filler, and PP grafted with maleic anhydride (PP-g-MA) as the compatibilizer, a MWCNTs/PP-g-MA masterbatch was prepared by using a solution blending method. Then, a lightweight, conductive PP/PTFE/MWCNTs composite foam was prepared by means of extruder granulation and supercritical nitrogen (ScN2) injection foaming. The composite foams were studied in terms of rheology, morphological, foaming behavior and mechanical properties. The results proved that the in situ fibrillation of PTFE can have a remarkable effect on melt strength and viscoelasticity, thus improving the foaming performance; we found that PP/3% PTFE showed excellent performance. Meanwhile, the addition of MWCNTs endows the material with conductive properties, and the conductivity reached was 2.73 × 10-5 S/m with the addition of 0.2 wt% MWCNTs. This study's findings are expected to be applied in the lightweight, antistatic and high-performance automotive industry.
ABSTRACT
Intimal hyperplasia, thrombosis formation, and delayed endothelium regeneration are the main causes that restrict the clinical applications of PTFE small-diameter vascular grafts (inner diameter < 6 mm). An ideal strategy to solve such problems is to facilitate in situ endothelialization. Since the natural vascular endothelium adheres onto the basement membrane, which is a specialized form of extracellular matrix (ECM) secreted by endothelial cells (ECs) and smooth muscle cells (SMCs), functionalizing PTFE with an ECM coating was proposed. However, besides ECs, the ECM-modified PTFE improved SMC growth as well, thereby increasing the risk of intimal hyperplasia. In the present study, heparin was immobilized on the ECM coating at different densities (4.89 ± 1.02 µg/cm2, 7.24 ± 1.56 µg/cm2, 15.63 ± 2.45 µg/cm2, and 26.59 ± 3.48 µg/cm2), aiming to develop a bio-favorable environment that possessed excellent hemocompatibility and selectively inhibited SMC growth while promoting endothelialization. The results indicated that a low heparin density (4.89 ± 1.02 µg/cm2) was not enough to restrict platelet adhesion, whereas a high heparin density (26.59 ± 3.48 µg/cm2) resulted in decreased EC growth and enhanced SMC proliferation. Therefore, a heparin density at 7.24 ± 1.56 µg/cm2 was the optimal level in terms of antithrombogenicity, endothelialization, and SMC inhibition. Collectively, this study proposed a heparin-immobilized ECM coating to modify PTFE, offering a promising means to functionalize biomaterials for developing small-diameter vascular grafts.
Subject(s)
Heparin , Polytetrafluoroethylene , Blood Vessel Prosthesis , Endothelial Cells , Endothelium, Vascular , Extracellular MatrixABSTRACT
Polyurethane foams (PUFs) are found everywhere in our daily life, but they suffer from poor fire resistance. In this study, expansible graphite (EG) as flame retardant was incorporated into PUFs to improve material fire resistance. With the presence of EGs in the PU matrix, bubble size in PUF became smaller as confirmed by the scanning electron microscopy. The mass density of PUFs is directly proportional to the content of EG additive. The compression strengths of EG0/PUF and EG30/PUF decrease from 0.51 MPa to 0.29 MPa. The Fourier transform infrared spectroscopy (FTIR) analysis of RPUFs showed that the addition of EGs did not change the functional group structures of RPUFs. Thermo-gravimetric analysis (TGA) testing results showed that the carbon residue weight of EG30/PUF is higher than other PU composite foams. The combination of TGA and FTIR indicated that the EG addition did not change the thermal decomposition products of EG0/PUF, but effectively inhibited its thermal decomposition rate. Cone calorimeter combustion tests indicated that the peak of the heat release rate of EG30/PUF significantly decreased to 100.5 kW m-2compared to 390.6 kW m-2for EG0/PUF. The ignition time of EG/PUF composites also increased from 2 s to 11 s with incorporation of 30 wt% EGs. The limiting oxygen index (LOI) and UL-94 standard tests show that the LOI of EG30/PUF can reach 55 vol%, and go through V-0 level. This study showed that adding EG into PU foams could significantly improve the thermal stability and flame retardancy properties of EG/PUF composites without significantly sacrificing material compression strength. The research results provide useful guidelines on industrial production and applications of PUFs.
ABSTRACT
Cardiovascular diseases, especially ones involving narrowed or blocked blood vessels with diameters smaller than 6 millimeters, are the leading cause of death globally. Vascular grafts have been used in bypass surgery to replace damaged native blood vessels for treating severe cardio- and peripheral vascular diseases. However, autologous replacement grafts are not often available due to prior harvesting or the patient's health. Furthermore, autologous harvesting causes secondary injury to the patient at the harvest site. Therefore, artificial blood vessels have been widely investigated in the last several decades. In this review, the progress and potential outlook of small-diameter blood vessels (SDBVs) engineered in vitro are highlighted and summarized, including material selection and development, fabrication techniques, surface modification, mechanical properties, and bioactive functionalities. Several kinds of natural and synthetic polymers for artificial SDBVs are presented here. Commonly used fabrication techniques, such as extrusion and expansion, electrospinning, thermally induced phase separation (TIPS), braiding, 3D printing, hydrogel tubing, gas foaming, and a combination of these methods, are analyzed and compared. Different surface modification methods, such as physical immobilization, surface adsorption, plasma treatment, and chemical immobilization, are investigated and are compared here as well. Mechanical requirements of SDBVs are also reviewed for long-term service. In vitro biological functions of artificial blood vessels, including oxygen consumption, nitric oxide (NO) production, shear stress response, leukocyte adhesion, and anticoagulation, are also discussed. Finally, we draw conclusions regarding current challenges and attempts to identify future directions for the optimal combination of materials, fabrication methods, surface modifications, and biofunctionalities. We hope that this review can assist with the design, fabrication, and application of SDBVs engineered in vitro and promote future advancements in this emerging research field.
Subject(s)
Biocompatible Materials/chemistry , Blood Vessel Prosthesis , Blood Vessels/chemistry , Tissue Scaffolds/chemistry , Humans , Materials Testing , Particle Size , Stress, Mechanical , Surface PropertiesABSTRACT
Oil spills in the ocean greatly threaten local environments, marine creatures, and coastal economies. An automatic water/oil separation material system was proposed in this study, and a tubular geometry was chosen to demonstrate the water/oil separation efficiency and effectiveness. The water/oil separation tubes were made of expanded polytetrafluoroethylene (ePTFE) and graphite composites. The permeation pressures of water and oil through the tube walls were tuned by adjusting the ePTFE microstructure, which, in turn, depended on the degree of expansion and the graphite content. Fourier-transform infrared spectroscopy was performed to confirm the compositions of the ePTFE/graphite composites, and a scanning electron microscope was used to examine the microstructure and morphology of the expanded PTFE/graphite composite tubes. When a proper pressure was applied, which was higher than the oil's permeation pressure (3.0 kPa) but lower than the water's permeation pressure (57 kPa), the oil leaked out of the tube walls while the water went through the ePTFE/graphite tubes. As such, the water/oil mixture could be separated and collected in different containers or an outer tube. Due to this automatic separation, the whole process could be done continuously and conveniently, thus exhibiting great potential in the practical applications of oil spill and water separation/remediation.
ABSTRACT
A new type of deacetylated cellulose acetate (DA)@polydopamine (PDA) composite nanofiber membrane was fabricated by electrospinning and surface modification. The membrane was applied as a highly efficient adsorbent for removing methylene blue (MB) from an aqueous solution. The morphology, surface chemistry, surface wettability, and effects of operating conditions on MB adsorption ability, as well as the equilibrium, kinetics, thermodynamics, and mechanism of adsorption, were systematically studied. The results demonstrated that a uniform PDA coating layer was successfully developed on the surface of DA nanofibers. The adsorption capacity of the DA@PDA nanofiber membrane reached up to 88.2 mg/g at a temperature of 25 °C and a pH of 6.5 after adsorption for 30 h, which is about 8.6 times higher than that of DA nanofibers. The experimental results showed that the adsorption behavior of DA@PDA composite nanofibers followed the Weber's intraparticle diffusion model, pseudo-second-order model, and Langmuir isothermal model. A thermodynamic analysis indicated that endothermic, spontaneous, and physisorption processes occurred. Based on the experimental results, the adsorption mechanism of DA@PDA composite nanofibers was also demonstrated.
ABSTRACT
Along with increasing oily, industrial wastewater and seawater pollution, oil spills-and their clean-up via the separation of oil and water-are still a worldwide challenge. Aiming to fabricate an oil/water separation membrane with excellent comprehensive performance, we report here a new type of multifunctional deacetylated cellulose acetate (d-CA) membrane. The cellulose acetate (CA) nanofiber membranes are fabricated by electrospinning and then deacetylated to obtain the d-CA nanofiber membranes, which are super-amphiphilic in air, oleophobic in water, and super-hydrophilic in oil. The multifunctional d-CA nanofiber membranes can be used as water-removal substances for oil/water mixtures, as well as emulsified oil/water and oil/corrosive aqueous systems, with gravity as the only needed driving force. The d-CA nanofiber membranes possess the highest separation flux, reaching up to 38,000 L/m2·h, and the highest separation efficiency, reaching up to 99.97 % for chloroform/water mixtures under the force of gravity. In fact, the separation flux was several times higher than that of commercial CA (c-CA) membranes. The excellent anti-pollution and self-cleaning abilities endow the membranes with powerful cyclic stability and reusability. The d-CA nanofiber membranes show great application prospects in chemical plants, textile mills, and the food industry, as well as offshore oil spills, to separate oil from water.
ABSTRACT
In this study, a small-diameter, double-layered eggshell membrane/thermoplastic polyurethane (ESM/TPU) vascular graft with a wavy structure was developed. The avian eggshell membrane, a fibrous structure similar to the extracellular matrix (ECM), has the potential to yield rapid endothelialization in vitro. The dopamine and heparin modification of the ESM surface not only promoted human umbilical vein endothelial cell (HUVEC) proliferation via cytocompatibility assessment, but also improved its anticoagulation properties as verified in platelet adhesion tests. The biomimetic mechanical properties of the vascular graft were provided by the elastic TPU fibers via electrospinning using a wavy cross-section rotating collector. The advantage of combining these two materials is to make use of the bioactivity of ESM as the internal membrane and the tunable mechanical properties of TPU as the external layer. The circumferentially wavy structure of the vascular graft produced a toe region in the non-linear section of the stress-strain curve similar to that of natural blood vessels. The ESM/TPU graft's circumferential ultimate strength was 2.57â¯MPa, its strain was 339% mm/mm, and its toe region was found to be around 20% mm/mm. Cyclical tension tests showed that the vascular graft could maintain good mechanical properties and showed no structural damage under repeated extension tests.
Subject(s)
Biocompatible Materials/chemistry , Blood Vessel Prosthesis , Egg Shell/chemistry , Polyurethanes/chemistry , Animals , Antithrombins , Chickens , Equipment Design , Extracellular Matrix/chemistry , Human Umbilical Vein Endothelial Cells , Humans , Particle Size , Platelet Adhesiveness/drug effectsABSTRACT
Treatment of cardiovascular diseases suffers from the lack of transplantable small-diameter blood vessel (SDBV) grafts that can prohibit/eliminate thrombosis. Although expanded poly(tetrafluoroethylene) (ePTFE) has the potential to be used for SDBV grafts, recurrence of thrombus remains the biggest challenge. In this study, a reactive oxygen species (ROS)-responsive antithrombogenic drug synthesis and a bulk coating process were employed to fabricate functional ePTFE grafts capable of prohibiting/eliminating blood clots. The synthesized drug that would release antiplatelet ethyl salicylate (ESA), in responding to ROS, was dissolved in a polycaprolactone (PCL) solution, followed by a bulk coating of the as-fabricated ePTFE grafts with the PCL/drug solution. Nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM) were employed to investigate and confirm the synthesis and presence of the ROS-responsive drug in the ePTFE grafts. The ESA release functions were demonstrated via the drug-release profile and dynamic anticoagulation tests. The biocompatibility of the ROS-responsive ePTFE grafts was demonstrated via lactate dehydrogenase (LDH) cytotoxicity assays, live and dead cell assays, cell morphology, and cell-graft interactions. The ROS-responsive, antithrombogenic ePTFE grafts provide a feasible way for maintaining long-term patency, potentially solving a critical challenge in SDBV applications.
Subject(s)
Fibrinolytic Agents/therapeutic use , Fluorocarbons/chemistry , Polymers/chemistry , Polytetrafluoroethylene/chemistry , Reactive Oxygen Species/metabolism , Animals , Humans , L-Lactate Dehydrogenase/metabolism , Magnetic Resonance Spectroscopy , Microscopy, Atomic Force , Polyesters/chemistry , Salicylates/chemistry , Spectroscopy, Fourier Transform Infrared , Thrombosis/drug therapyABSTRACT
Viable tissue-engineering small-diameter vascular grafts should support rapid growth of an endothelial cell layer and exhibit long-term antithrombogenic property. In this study, multiple layers of various bioactive molecules, such as vascular endothelial growth factor (VEGF) and heparin, on an electrospun polycaprolactone scaffold have been developed through repeated electrostatic adsorption self-assembly (up to 20 layers), followed by genipin cross-linking. Programmed and sustained release of biomolecules embedded within the multilayered structure can be triggered by matrix metallopeptidase 2 enzyme in vitro. The result is an early and full release of VEGF to promote rapid endothelialization on the intended vascular grafts, followed by a gradual but sustained release of heparin for long-term anticoagulation and antithrombogenicity. This method of forming a biologically responsive, multimodal delivery of VEGF and heparin is highly suitable for all hydrophobic surfaces and provides a promising way to meet the critical requirements of engineered small-diameter vascular grafts.