This study aimed to elucidate the impact of advanced glycation end products (AGEs) and glucose shock on cardiomyocyte viability, gene expression, cardiac biomarkers, and cardiac contractility. Firstly, AGEs were generated in-house, and their concentration was confirmed using absorbance measurements. AC16 cardiomyocytes were then exposed to varying doses of AGEs, resulting in dose-dependent decreases in cell viability.
View Article and Find Full Text PDFParkinson's disease (PD), a progressive central nervous system disorder marked by involuntary movements, poses a significant challenge in neurodegenerative research due to the gradual degeneration of dopaminergic (DA) neurons. Early diagnosis and understanding of PD's pathogenesis could slow disease progression and improve patient management. In vitro modeling with DA neurons derived from human-induced pluripotent stem cell-derived neural progenitor cells (NPCs) offers a promising approach.
View Article and Find Full Text PDFStereolithography (SLA) 3D printing is a rapid prototyping technique and reproducible manufacturing platform, which makes it a useful tool to develop advanced microfluidic devices for bioanalytical applications. However, limited information exists regarding the physical, chemical, and biological properties of the photocured polymers printed with SLA. This study demonstrates the characterization of a commercially available SLA 3D printed polymer to evaluate the potential presence of any time-dependent changes in material properties that may affect its ability to produce functional, capillary-action microfluidic devices.
View Article and Find Full Text PDFHeart diseases cause over 17.9 million total deaths globally, making them the leading source of mortality. The aim of this review is to describe the characteristic mechanical, chemical and cellular properties of human cardiac tissue and how these properties can be mimicked in 3D bioprinted tissues.
View Article and Find Full Text PDFThis study implemented the application of microcomputed tomography (micro-CT) as a characterization technique for the study and investigation of the microstructure of 3D scaffold structures produced via three-dimensional bioprinting (3DBP). The study focused on the preparation, characterization, and cytotoxicity analysis of gold nanoparticles (Au-NPs) incorporated into 3DBP hydrogels for micro-CT evaluation. The Au-NPs were characterized by using various techniques, including UV-vis spectrometry, dynamic light scattering (DLS), zeta potential measurement, and transmission electron microscopy (TEM).
View Article and Find Full Text PDFIn this study, we designed a tissue-engineered neurocardiac model to help us examine the role of neuronal regulation and confirm the importance of neural innervation techniques for the regeneration of cardiac tissue. A three-dimensional (3D) bioprinted neurocardiac scaffold composed of a mixture of gelatin-alginate and alginate-genipin-fibrin hydrogels was developed with a 2:1 ratio of AC16 cardiomyocytes (CMs) and retinoic acid-differentiated SH-SY5Y neuronal cells (NCs) respectively. A unique semi-3D bioprinting approach was adopted, where the CMs were mixed in the cardiac bioink and printed using an anisotropic accordion design to mimic the physiological tissue architecture in vivo.
View Article and Find Full Text PDFHuman cardiovascular tissue and diseases are difficult to study for novel drug discovery and fundamental cellular/molecular processes due to limited availability of physiologically-relevant models in vitro.[1-3] Animal models may resemble human heart structure, however there are significant differences from human cardiovascular physiology including biochemical signaling, and gene expression.[4-6] In vitro microfluidic tissue models provide a less expensive, more controlled, and reproducible platform for better quantification of isolated cellular processes in response to biochemical or biophysical stimulus.
View Article and Find Full Text PDFDoxorubicin (DOX) is a highly effective anthracycline chemotherapy agent effective in treating a broad range of life-threatening malignancies but it causes cardiotoxicity in many subjects. While the mechanism of its cardiotoxic effects remains elusive, DOX-related cardiotoxicity can lead to heart failure in patients. In this study, we investigated the effects of DOX-induced cardiotoxicity on human cardiomyocytes (CMs) using a three-dimensional (3D) bioprinted cardiac spheroidal droplet based-system in comparison with the traditional two-dimensional cell (2D) culture model.
View Article and Find Full Text PDFHyperglycemia-mediated cardiac dysfunction is an acute initiator in the development of vascular complications, leading to cardiac fibrosis. To investigate the effects of hyperglycemia-mediated changes in cardiomyocytes, cells were cultured in-vitro under normoglycemic (5 mM or 25 mM D-glucose) and hyperglycemic (5 → 50 mM or 25 → 50 mM D-glucose) conditions, respectively. After 24-h of hyperglycemic exposure, cells were collected for RNA-sequencing (RNA-seq) studies to further investigate the differentially expressed genes (DEG) related to inflammation and fibrosis in samples cultured under hyperglycemic-in comparison with normoglycemic-conditions.
View Article and Find Full Text PDF3D bioprinting offers a simplified solution for the engineering of complex tissue parts for in-vitro drug discovery or, in-vivo implantation. However, significant amount of challenges exist in 3D bioprinting of neural tissues, as these are sensitive cell types to handle via extrusion bioprinting techniques. We assessed the feasibility of bioprinting human neural progenitor cells (NPCs) in 3D hydrogel lattices using a fibrinogen-alginate-chitosan bioink, previously optimized for neural-cell growth, and subsequently modified for structural support during extrusion printing, in this study.
View Article and Find Full Text PDFCardiac organoids are 3-dimensional (3D) structures composed of tissue or niche-specific cells, obtained from diverse sources, encapsulated in either a naturally derived or synthetic, extracellular matrix scaffold, and include exogenous biochemical signals such as essential growth factors. The overarching goal of developing cardiac organoid models is to establish a functional integration of cardiomyocytes with physiologically relevant cells, tissues, and structures like capillary-like networks composed of endothelial cells. These organoids used to model human heart anatomy, physiology, and disease pathologies in vitro have the potential to solve many issues related to cardiovascular drug discovery and fundamental research.
View Article and Find Full Text PDFIn this study, three types of electrospun scaffolds, including furfuryl-gelatin (f-gelatin) alone, f-gelatin with polycaprolactone (PCL) in a 1:1 ratio, and coaxial scaffolds with PCL (core) and f-gelatin (sheath), were developed for tissue engineering applications. Scaffolds were developed through single nozzle electrospinning and coaxial electrospinning, respectively, to serve as scaffolds for cardiac tissue engineering. Uniform fibrous structures were revealed in the scaffolds with significantly varying average fiber diameters of 760 ± 80 nm (f-gelatin), 420 ± 110 nm [f-gelatin and PCL (1:1)], and 810 ± 60 nm (coaxial f-gelatin > PCL) via scanning electron microscopy.
View Article and Find Full Text PDFIn this study, we developed three-dimensional (3D) printed annular ring-like scaffolds of hydrogel (gelatin-alginate) constructs encapsulated with a mixture of human cardiac AC16 cardiomyocytes (CMs), fibroblasts (CFs), and microvascular endothelial cells (ECs) as cardiac organoid models in preparation for investigating the role of microgravity in cardiovascular disease initiation and development. We studied the mechanical properties of the acellular scaffolds and confirmed their cell compatibility as well as heterocellular coupling for cardiac tissue engineering. Rheological analysis performed on the acellular scaffolds showed the scaffolds to be elastogenic with elastic modulus within the range of a native heart tissue.
View Article and Find Full Text PDFMyocardial fibrosis is one of the major complications of long-term diabetes. Hyperglycemia induced cardiomyocyte atrophy is a frequent pathophysiological indicator of diabetic heart. The objective of this study was to investigate the cardioprotective effect of glycyrrhizin (GLC) on myocardial damage in diabetic rats and assess the anti-inflammatory and anti-fibrotic effect of GLC.
View Article and Find Full Text PDFBone tissue engineering (BTE) aims to develop strategies to regenerate damaged or diseased bone using a combination of cells, growth factors, and biomaterials. This article highlights recent advances in BTE, with particular emphasis on the role of the biomaterials as scaffolding material to heal bone defects. Studies encompass the utilization of bioceramics, composites, and myriad hydrogels that have been fashioned by injection molding, electrospinning, and 3D bioprinting over recent years, with the aim to provide an insight into the progress of BTE along with a commentary on their scope and possibilities to aid future research.
View Article and Find Full Text PDFPurpose: To develop a novel model composed solely of Col I and Col III with the lower and upper limits set to include the ratios of Col I and Col III at 3:1 and 9:1 in which the structural and mechanical behavior of the resident CM can be studied. Further, the progression of fibrosis due to change in ratios of Col I:Col III was tested.
Methods: Collagen gels with varying Col I:Col III ratios to represent a healthy (3:1) and diseased myocardial tissue were prepared by manually casting them in wells.
Since conventional human cardiac two-dimensional (2D) cell culture and multilayered three-dimensional (3D) models fail in recapitulating cellular complexity and possess inferior translational capacity, we designed and developed a high-throughput scalable 3D bioprinted cardiac spheroidal droplet-organoid model with cardiomyocytes and cardiac fibroblasts that can be used for drug screening or regenerative engineering applications. This study helped establish the parameters for bioprinting and cross-linking a gelatin-alginate-based bioink into 3D spheroidal droplets. A flattened disk-like structure developed in prior studies from our laboratory was used as a control.
View Article and Find Full Text PDFLigation of the left anterior descending (LAD) coronary artery has been commonly employed to induce myocardial infarction (MI) in animals; however, it is known to pose setbacks in the form of cardiac arrhythmias and unpredictable areas of necrotic damage. Cryo-infarction is an alternate method that has been adopted to create a reproducible model of a myocardial injury. In this study, Sprague-Dawley rats were subjected to thoracotomy followed by cryo-induced infarction of the heart, while the control-sham group was only subjected to thoracotomy following which the heart was collected from all animals.
View Article and Find Full Text PDFHydrogels are a class of biomaterials used for a wide range of biomedical applications, including as a three-dimensional (3D) scaffold for cell culture that mimics the extracellular matrix (ECM) of native tissues. To understand the role of the ECM in the modulation of cardiac cell function, alginate was used to fabricate crosslinked gels with stiffness values that resembled embryonic (2.66 ± 0.
View Article and Find Full Text PDFIntroduction: In this in-vitro study, we designed a 3D printed composite of zinc oxide (ZnO) nanoparticles (NPs) with photocatalytic activities encapsulated within hydrogel (alginate) constructs, for antibacterial purposes applicable towards wound healing. We primarily sought to confirm the mechanical properties and cell compatibility of these ZnO NP infused scaffolds.
Methods: The antibacterial property of the ZnO NPs was confirmed by hydroxyl radical generation using ultraviolet (U.
In this study, fibrin was added to a photo-polymerizable gelatin-based bioink mixture to fabricate cardiac cell-laden constructs seeded with human induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) or CM cell lines with cardiac fibroblasts (CF). The extensive use of platelet-rich fibrin, its capacity to offer patient specificity, and the similarity in composition to surgical glue prompted us to include fibrin in the existing bioink composition. The cell-laden bioprinted constructs were cross-linked to retain a herringbone pattern via a two-step procedure including the visible light cross-linking of furfuryl-gelatin followed by the chemical cross-linking of fibrinogen via thrombin and calcium chloride.
View Article and Find Full Text PDFIn this study, we used an alginate-gelatin bioink to design and print 3D constructs with lattice, honeycomb and fibrous bundle patterns. These designs were printed using a small-scale laboratory printer, at first and later translated to a larger scale, high throughput-printing platform. A comparative analysis of the structures printed using two dissimilar platforms using gross morphologic evaluation, scanning electron microscopy and swelling assay confirmed our hypothesis that a design printed using a small-scale laboratory bioprinter for optimization of bioink composition and printing parameters can be successfully translated into a large scale-printing platform for high throughput printing of constructs.
View Article and Find Full Text PDFIn this study, we designed, synthesized, and characterized ultrahigh purity single-walled carbon nanotube (SWCNT)-alginate hydrogel composites. Among the parameters of importance in the formation of an alginate-based hydrogel composite with single-walled carbon nanotubes, are their varying degrees of purity, their particulate agglomeration and their dose-dependent correlation to cell viability, all of which have an impact on the resultant composite's efficiency and effectiveness towards cell-therapy. To promote their homogenous dispersion by preventing agglomeration of the SWCNT, three different surfactants-sodium dodecyl sulfate (SDS-anionic), cetyltrimethylammonium bromide (CTAB-cationic), and Pluronic F108 (nonionic)-were utilized.
View Article and Find Full Text PDFCardiovascular tissue engineering endeavors to repair or regenerate damaged or ineffective blood vessels, heart valves, and cardiac muscle. Current strategies that aim to accomplish such a feat include the differentiation of multipotent or pluripotent stem cells on appropriately designed biomaterial scaffolds that promote the development of mature and functional cardiac tissue. The advent of additive manufacturing 3D bioprinting technology further advances the field by allowing heterogenous cell types, biomaterials, and signaling factors to be deposited in precisely organized geometries similar to those found in their native counterparts.
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