Design and Synthesis of P(AAm-co-NaAMPS)-Alginate-Xanthan Hydrogels and the Study of Their Mechanical and Rheological Properties in Artificial Vascular Graft Applications.

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.

Anti-thrombotic poly(AAm-co-NaAMPS)-xanthan hydrogel-expanded polytetrafluoroethylene (ePTFE) vascular grafts with enhanced endothelialization and hemocompatibility properties.

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.

The Study on the Morphology and Compression Properties of Microcellular TPU/Nanoclay Tissue Scaffolds for Potential Tissue Engineering Applications.

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.

The Injected Foaming Study of Polypropylene/Multiwall Carbon Nanotube Composite with In Situ Fibrillation Reinforcement.

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.

Conventional and Microcellular Injection Molding of a Highly Filled Polycarbonate Composite with Glass Fibers and Carbon Black.

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.

Effects of expandable graphite on the flame-retardant and mechanical performances of rigid polyurethane foams.

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.

Surface modification of polytetrafluoroethylene (PTFE) with a heparin-immobilized extracellular matrix (ECM) coating for small-diameter vascular grafts applications.

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.

Viscosity characterization and flow simulation and visualization of polytetrafluoroethylene paste extrusion using a green and biofriendly lubricant.

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.

Expanded Polytetrafluoroethylene/Graphite Composites for Easy Water/Oil Separation.

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.

Biologically Functionalized Expanded Polytetrafluoroethylene Blood Vessel Grafts.

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.

Expanded Poly(tetrafluoroethylene) Blood Vessel Grafts with Embedded Reactive Oxygen Species (ROS)-Responsive Antithrombogenic Drug for Elimination of Thrombosis.

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.

Axial-Circular Magnetic Levitation: A Three-Dimensional Density Measurement and Manipulation Approach.

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.

Highly Efficient Removal of Methylene Blue Dye from an Aqueous Solution Using Cellulose Acetate Nanofibrous Membranes Modified by Polydopamine.

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.

Artificial small-diameter blood vessels: materials, fabrication, surface modification, mechanical properties, and bioactive functionalities.

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.

Dual super-amphiphilic modified cellulose acetate nanofiber membranes with highly efficient oil/water separation and excellent antifouling properties.

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.

Wavy small-diameter vascular graft made of eggshell membrane and thermoplastic polyurethane.

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 2.57 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.

Oxygen-Rich Polymers as Highly Effective Positive Tribomaterials for Mechanical Energy Harvesting.

Triboelectric nanogenerators (TENGs) are a potential solution to the depleted state of fossil fuels, on the condition that the energy conversion efficiency can be further improved. Tribomaterials are important not only for improving the output performance of TENGs but also for extending their applications. In this work, a poly-ε-caprolactone (PCL) electrospun membrane is proposed as a highly effective positive tribomaterial, paired with an expanded polytetrafluoroethylene (ePTFE) membrane, to fabricate TENGs (PCL/ePTFE TENGs). Compared with a widely used polyamide-6 (PA6)/ePTFE TENG, the output performance of the PCL/ePTFE TENG is enhanced by about 28%, indicating that PCL possesses a stronger electron-donating ability owing to the existence of oxygen-containing functional groups as electron donors. Furthermore, the PCL membrane is modified using poly(ethylene glycol) methyl ether (mPEG), which possesses more O atoms, by electrospinning (ES) and dip coating (DC). The results reveal that mPEG is very effective at improving the positive electron polarity of PCL. With the increase of mPEG content, the output performance increases by more than 40%, yielding a maximum power density of 115.83 W·m-2. More polymers have been compared to confirm that many oxygen-rich polymers show excellent electron-donating abilities and act as highly efficient positive tribomaterials. This work also provides additional options for more effective positive tribomaterials.

Programmed Release of Multimodal, Cross-Linked Vascular Endothelial Growth Factor and Heparin Layers on Electrospun Polycaprolactone Vascular Grafts.

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.

Micro-injection molded, poly(vinyl alcohol)-calcium salt templates for precise customization of 3D hydrogel internal architecture.

In tissue engineering applications, sacrificial molding of hydrogel monoliths is a versatile technique for creating 3D molds to control tissue morphology. Previous sacrificial templates fabricated by serial processes such as solvent casting and thermal extrusion/fiber drawing can be used to effectively mold internal geometries within rapidly polymerizing, bulk curing hydrogels. However, they display poorer performance in controlling the geometry of diffusion limited, ionically cross-linked hydrogels, such as alginate. Here, we describe the use of poly(vinyl alcohol)-calcium salt templates (PVOH-Ca) fabricated by micro-injection molding, a parallel mass-production process, to conveniently cast internal geometries within both bulk curing hydrogels and ionically cross-linked alginate hydrogels. Calcium salt solubility was discovered to be a critical factor in optimizing the polymer composite's manufacturability, mechanical properties, and the quantity of calcium released upon template dissolution. Metrological and computed tomography (CT) analysis showed that the template's calcium release enables precise casting of microscale channel geometries within alginate hydrogels (6.4 ±â€¯7.2% average error). Assembly of modular PVOH-Ca templates to mold 3D channel networks within alginate hydrogels is presented to demonstrate engineering scalability. Moreover, the platform is used to create hydrogel molds for engineering human embryonic stem cell (hESC)-derived neuroepithelial organoids of a microscale, biomimetic cylindrical morphology. Thus, injection molded PVOH-Ca templates facilitate customization of hydrogel sacrificial molding, which can be used to generate 3D hydrogels with complex internal microscale architecture for diverse tissue engineering applications. STATEMENT OF SIGNIFICANCE: Sacrificial molding of hydrogel monoliths is a versatile technique for creating 3D molds for tissue engineering applications. Previous sacrificial materials fabricated by serial processes have been used to effectively mold internal geometries within rapidly polymerizing, bulk curing hydrogels. However, they display poor performance in molding geometry within diffusion limited, ionically cross-linked hydrogels, e.g. alginate. We describe the use of poly(vinyl alcohol)-calcium salt templates (PVOH-Ca) fabricated by micro-injection molding, an unparalleled mass-production process, to conveniently cast internal geometries within both bulk curing hydrogels and ionically cross-linked alginate hydrogels. Calcium release from the PVOH-Ca templates enables precise sacrificial molding of alginate hydrogels and the process is biocompatible. Moreover, we demonstrate its use to engineer the morphology of hPSC-derived neuroepithelial organoids, and modular PVOH-Ca template designs can be assembled to enable scalable 3D customization of hydrogel internal architecture.

Fabrication of triple-layered vascular grafts composed of silk fibers, polyacrylamide hydrogel, and polyurethane nanofibers with biomimetic mechanical properties.

Mimicking the mechanical properties of native tissue is an important requirement for tissue engineering scaffolds. Blood vessels are subject to repetitive dilation and contraction and possess a special nonlinear mechanical property due to their triple-layered structure. Fabrication of vascular grafts consisting of bioresorbable materials with biomimetic mechanical properties is an urgent demand, as well as a critical challenge. Inspired by the configuration and function of collagen and elastin in native blood vessels, a new type of triple-layered vascular graft (TLVG) was developed in this study. The TLVGs were composed of braided silk as the inner layer, polyacrylamide (PAM) hydrogel as the middle layer, and electrospun thermoplastic polyurethane (TPU) as the outer layer. The woven-structured silk fibers were able to mimic the properties of the loosely distributed collagen fibers, while the highly elastic PAM hydrogel and TPU nanofibers mimicked the elasticity of elastin in the blood vessel. With this specially designed microstructure and combination of rigid and elastic materials, the TLVGs successfully mimicked the nonlinear mechanical property of native blood vessels. Moreover, TLVGs possess sufficient suture retention strength for surgical implantation. The introduction of a PAM hydrogel layer effectively solved the leaking issue for conventional porous vascular grafts and greatly enhanced the burst pressure. In addition, all materials used have high biocompatibility to human endothelial cells, which indicates that the developed TLVGs have high potential to be used as readily available vascular grafts.