Cardiovascular disease is currently the top global cause of death, however, research into new therapies is in decline. Tissue engineering is a solution to this crisis and in combination with the use of carbon nanotubes (CNTs), which have drawn recent attention as a biomaterial, could facilitate the development of more dynamic and complex in vitro models. CNTs’ electrical conductivity and dimensional similarity to cardiac extracellular proteins provide a unique opportunity to deliver scaffolds with stimuli that mimic the native cardiac microenvironment in vitro more effectively. This systematic review aims to evaluate the use and efficacy of CNTs for cardiac tissue scaffolds and was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Three databases were searched: PubMed, Scopus, and Web of Science. Papers resulting from these searches were then subjected to analysis against pre-determined inclusion and quality appraisal criteria. From 249 results, 27 manuscripts met the criteria and were included in this review. Neonatal rat cardiomyocytes were most commonly used in the experiments, with multi-walled CNTs being most common in tissue scaffolds. Immunofluorescence was the experimental technique most frequently used, which was employed for the staining of cardiac-specific proteins relating to contractile and electrophysiological function.
Electrical conductivity is of great significance to cardiac tissue engineering and permits the use of electrical stimulation in mimicking cardiac pacing. The development of biomaterials for tissue engineering can incorporate physical properties that are uncommon to standard cell culture and can facilitate improved cardiomyocyte function. In this review, the PICOT question asks, "How has the application of external electrical stimulation in conductive scaffolds for tissue engineering affected cardiomyocyte behavior in in vitro cell culture?" The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, with predetermined inclusion and quality appraisal criteria, were used to assess publications from PubMed, Web of Science, and Scopus. Results revealed carbon nanotubes to be the most common conductive agent in biomaterials and rodent-sourced cell types as the most common cardiomyocytes used. To assess cardiomyocytes, immunofluorescence was used most often, utilizing proteins, such as connexin 43, cardiac α-actinin, and cardiac troponins. It was determined that the modal average stimulation protocol comprised 1-3 V square biphasic 50-ms pulses at 1 Hz, applied toward the end of cell culture. The addition of electrical stimulation to in vitro culture has exemplified it as a powerful tool for cardiac tissue engineering and brings researchers closer to creating optimal artificial cardiac tissue constructs.
There is a significant need to understand the complexity and heterogeneity of articular cartilage to develop more effective therapeutic strategies for diseases such as osteoarthritis. Here, we show that carbon nanotubes (CNTs) are excellent candidates as a material for synthetic scaffolds to support the growth of chondrocytes—the cells that produce and maintain cartilage. Chondrocyte morphology, proliferation, and alignment were investigated as nanoscale CNT networks were applied to macroscopically textured polydimethylsiloxane (PDMS) scaffolds. The application of CNTs to the surface of PDMS‐based scaffolds resulted in an up to 10‐fold increase in cell adherence and 240% increase in proliferation, which is attributable to increased nanoscale roughness and hydrophilicity. The introduction of macroscale features to PDMS induced alignment of chondrocytes, successfully mimicking the cell behavior observed in the superficial layer of cartilage. Raman spectroscopy was used as a noninvasive, label‐free method to monitor extracellular matrix production and chondrocyte phenotype. Chondrocytes on these scaffolds successfully produced collagen, glycosaminoglycan, and aggrecan. This study demonstrates that introducing physical features at different length scales allows for a high level of control over tissue scaffold design and, thus, cell behavior. Ultimately, these textured scaffolds can serve as platforms to improve the understanding of osteoarthritis and for early‐stage therapeutic testing.
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