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.

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.

Fabrication and modification of wavy multicomponent vascular grafts with biomimetic mechanical properties, antithrombogenicity, and enhanced endothelial cell affinity.

A mismatch of mechanical properties and a high rate of thromboses are two critical challenges of creating viable artificial small-diameter vascular grafts (SDVGs). Herein, we propose a method to fabricate wavy multicomponent vascular grafts (WMVGs) via electrospinning using an assembled rotating collector. The WMVGs consisted of a wavy silk/poly(lactic acid) (PLA) inner layer and a thermoplastic polyurethane (TPU) outer layer, which mimic the structures and properties of collagen and elastin in native blood vessels, respectively. Attributed to the wavy structure and the combination of rigid silk/PLA and elastic TPU biomaterials, WMVGs are capable of mimicking the nonlinear tensile stress-strain relationship and "toe region" of native blood vessels. In addition, they have sufficient mechanical strength to meet implantation requirements in terms of tensile strength, suture retention, and burst pressure. Further modification of silk/PLA fibers with dopamine and heparin gave the grafts antithrombogenic properties and greatly enhanced endothelial cell affinities. Human umbilical vein endothelial cells (HUVECs) cultured on modified silk/PLA showed high viability, high proliferation rate, and favorable cell-substrate interactions. Moreover, HUVECs were able to fully cover and freely migrate upward on the lumen of the modified WMVGs without needing a special circulation bioreactor. Therefore, the modified WMVGs possessed biomimetic properties, antithrombogenicity, and enhanced endothelialization, making them a promising candidate for SDVGs. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2397-2408, 2019.