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A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig.

ABSTRACT: Globally, millions of patients are affected by myocardial infarction or lower limb gangrene/amputation due to atherosclerosis. Available surgical treatment based on vein and synthetic grafts provides sub-optimal benefits. We engineered a highly flexible and mechanically robust nanotextile-based vascular graft (NanoGraft) by interweaving nanofibrous threads of poly-L-lactic acid to address the unmet need. The NanoGrafts were rendered impervious with selective fibrin deposition in the micropores by pre-clotting. The pre-clotted NanoGrafts (4 mm diameter) and ePTFE were implanted in a porcine carotid artery replacement model. The fibrin-laden porous milieu facilitated rapid endothelization by the transmural angiogenesis in the NanoGraft. In-vivo patency of NanoGrafts was 100% at 2- and 4-weeks, with no changes over time in lumen size, flow velocities, and minimal foreign-body inflammatory reaction. However, the patency of ePTFE at 2-week was 66% and showed marked infiltration, neointimal thickening, and poor host tissue integration. The study demonstrates the in-vivo feasibility and safety of a thin-layered vascular prosthesis, viz., NanoGraft, and its potential superiority over the commercial ePTFE.

SUBMITTER: Joseph J

PROVIDER: S-EPMC8822766 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig.

Joseph John J Domenico Bruno Vito V Sulaiman Nadiah N Ward Alexander A Johnson Thomas W TW Baby Helna Mary HM Kerala Varma Praveen P Jose Rajesh R Nair Shantikumar V SV Menon Deepthy D George Sarah Jane SJ Ascione Raimondo R

Journal of nanobiotechnology 20220208 1

Globally, millions of patients are affected by myocardial infarction or lower limb gangrene/amputation due to atherosclerosis. Available surgical treatment based on vein and synthetic grafts provides sub-optimal benefits. We engineered a highly flexible and mechanically robust nanotextile-based vascular graft (NanoGraft) by interweaving nanofibrous threads of poly-L-lactic acid to address the unmet need. The NanoGrafts were rendered impervious with selective fibrin deposition in the micropores b ...[more]

PMID: 35135545

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Project description:Combining synthetic polymers and biomacromolecules prevents the occurrence of thrombogenicity and intimal hyperplasia in small-diameter vascular grafts (SDVGs). In the present study, an electrospinning poly (L)-lactic acid (PLLA) bilayered scaffold is developed to prevent thrombosis after implantation by promoting the capture and differentiation of endothelial colony-forming cells (ECFCs). The scaffold consists of an outer PLLA scaffold and an inner porous PLLA biomimetic membrane combined with heparin (Hep), peptide Gly-Gly-Gly-Arg-Glu-Asp-Val (GGG-REDV), and vascular endothelial growth factor (VEGF). Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and contact angle goniometry were performed to determine successful synthesis. The tensile strength of the outer layer was obtained using the recorded stress/strain curves, and hemocompatibility was evaluated using the blood clotting test. The proliferation, function, and differentiation properties of ECFCs were measured on various surfaces. Scanning electronic microscopy (SEM) was used to observe the morphology of ECFCs on the surface. The outer layer of scaffolds exhibited a similar strain and stress performance as the human saphenous vein via the tensile experiment. The contact angle decreased continuously until it reached 56° after REDV/VEGF modification, and SEM images of platelet adhesion showed a better hemocompatibility surface after modification. The ECFCs were captured using the REDV + VEGF + surface successfully under flow conditions. The expression of mature ECs was constantly increased with the culture of ECFCs on REDV + VEGF + surfaces. SEM images showed that the ECFCs captured by the REDV + VEGF + surface formed capillary-like structures after 4 weeks of culture. The SDVGs modified by REDV combined with VEGF promoted ECFC capture and rapid differentiation into ECs, forming capillary-like structures in vitro. The bilayered SDVGs could be used as vascular devices that achieved a high patency rate and rapid re-endothelialization.

Project description:Pulmonary arterial hypertension (PAH) imposes substantial pressure overload on the right ventricular free wall (RVFW), leading to myofiber hypertrophy and remodeling of its collagen fiber architecture. The transmural nature of these adaptations and their effects on the macroscopic mechanical behavior of the RVFW remain largely unexplored. In the present work, we extended our constitutive model for RVFW myocardium to investigate the transmural mechanical and structural remodeling post-PAH. Recent murine experimental studies provided us with comprehensive histomorphological and biaxial mechanical data for viable, passive myocardium for normal and post hypertensive cases. Multiple fiber-level remodeling events were found to be localized in the midwall region (40% < depth < 60%): (i) reorientation and alignment of both myo- and collagen fibers towards longitudinal (apex-to-outflow tract) direction, (ii) substantial increase in the rate of the recruitment of collagen fibers with strain, and (iii) a corresponding increase in the mechanical interactions between the collagen and myofibers. These adaptations suggest a denser and more fibrous connective tissue in the midwall region, and led to a substantially stiffer mechanical response along the longitudinal direction in post-PAH tissues. Moreover, using a Laplace-type mechanical equilibrium analysis of the right ventricle to approximate the wall stress state, we estimated that the longitudinal component of stress remained higher in the hypertensive state while the circumferential component approximately maintained homeostasis values. This result was consistent with our observation from the fiber- and tissue-level remodeling that longitudinally oriented collagen fibers, localized in the midwall region, dominated the remodeling process. The findings of this study highlight the need for more integrated cellular-tissue-organ analysis to better understand the remodeling events during PAH and design interventions.

Dataset Information

A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig.

Publications

A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig.

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