Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular application

Abstract

Background: Recent advances in nanotechnology (materials with at least one dimension between 1 nm and 100 nm) have led to the use of nanomaterials in numerous medical device applications. Recently, nanomaterials have been used to create innovative biomaterials for cardiovascular applications. Specifically, carbon nanofibers (CNF) embedded in poly(lacticco-glycolic-acid) (PLGA) have been shown to promote cardiomyocyte growth compared with conventional polymer substrates, but the mechanisms involved in such events remain unknown. The aim of this study was to determine the basic mechanism of cell growth on these novel nanocomposites. Methods: CNF were added to biodegradable PLGA (50:50 PGA:PLA weight ratio) to increase the conductivity, mechanical and cytocompatibility properties of pure PLGA. For this reason, different PLGA to CNF ratios (100:0, 75:25, 50:50, 25:75, and 0:100 wt%) with different PLGA densities (0.1, 0.05, 0.025, and 0.0125 g/mL) were used, and their compatibility with cardiomyocytes was assessed. Results: Throughout all the cytocompatibility experiments, cardiomyocytes were viable and expressed important biomarkers, including cardiac troponin T, connexin-43, and alpha-sarcomeric actin (α-SCA). Adhesion and proliferation experiments indicated that a PLGA density of 0.025 g/mL with a PLGA to CNF ratio of 75:25 and 50:50 (wt%) promoted the best overall cell growth, ie, a 55% increase in cardiomyocyte density after 120 hours compared with pure PLGA and a 75% increase compared with the control at the same time point for 50:50 (wt%). The PLGA:CNF materials were conductive, and their conductivity increased as greater amounts of CNF were added to pure PLGA, from 0 S ⋅ m −1 for pure PLGA (100:0 wt%) to 5.5 × 10 −3 S ⋅ m −1 for pure CNF (0:100 wt%), as compared with natural heart tissue (ranging from 0.16 S ⋅ m −1 longitudinally to 0.005 S ⋅ m −1 transversely). Tensile tests showed that the addition of CNF increased the tensile strength to mimic that of natural heart tissue, ie, 0.15 MPa for 100% PLGA to 5.41 MPa for the 50:50 (PLGA to CNF [wt%:wt%]) ratio at 0.025 g/mL. Atomic force microscopy indicated that the addition of CNF to PLGA increased the material surface area from 10% (100:0 [PLGA to carbon nanofiber (wt%:wt%)]) to over 60% (50:50 [PLGA to carbon nanofibers (wt%:wt%)]). Lastly, the adsorption of specific proteins (fibronectin and vitronectin) showed significantly more adsorption for the 50:50 PLGA to CNF (wt%:wt%) ratio at 0.025 g/mL PLGA compared with pure PLGA, which may be why cardiomyocyte function increased on CNF-enriched composites. Conclusion:This study demonstrates that cardiomyocyte function was enhanced on 50:50 PLGA to CNF (wt%:wt%) composite ratios at 0.025 g/mL PLGA densities because they mimicked native heart tissue tensile strength/conductivity and increased the adsorption of proteins known to promote cardiomyocyte function.

Study of 1D and 2D Carbon Nanomaterial in Alginate Films

“…These filamentous carbon nanomaterials (CNMs) possess excellent physical properties and, in comparison with GO, they have lower price and higher electrical conductivity [18]. Thus, CNFs can be utilized to fabricate conductive composites [19] for biomedical applications [20].…”

Low-Cost Advanced Hydrogels of Calcium Alginate/Carbon Nanofibers with Enhanced Water Diffusion and Compression Properties

“…Thus, these curved graphitic materials are nowadays employed in industrial fields such as polymer additives, gas storage materials, and catalyst supports [32]. Additionally, it has been demonstrated that composites with CNFs are able to promote cardiomyocyte growth [33] and neural regeneration [34] in biomedicine.…”

Biomimetic Microstructure Morphology in Electrospun Fiber Mats is Critical for Maintaining Healthy Cardiomyocyte Phenotype

“…Hence, we created synthetic substrates using a widely used polymer (PCL) 30 with a modulus similar to cardiac tissue 31, 32 (reported in our previous study 33 ). This polymer was spin-coated into a flat uniform sheet (as a control with morphology similar to TCPS) as well as electrospun into aligned/less aligned fibers to create structures similar to those found in the human heart.…”