Cardiac tissue engineering is a promising strategy to prevent heart failure. However, several issues remain unsolved, including efficient electrical coupling and incorporating factors to enhance tissue maturation and vascularization. Herein, a biohybrid hydrogel that enhances beating properties of engineered cardiac tissues and allows drug release concurrently is developed. Gold nanoparticles (AuNPs) with different sizes (18–241 nm) and surface charges (33.9–55.4 mV) are synthesized by reducing gold (III) chloride trihydrate using branched polyethyleneimine (bPEI). These nanoparticles increase gel stiffness from ≈91 to ≈146 kPa, enhance electrical conductivity of collagen hydrogels from ≈40 to 49–68 mS cm−1, and allow slow and steady release of loaded drugs. Engineered cardiac tissues based on bPEI‐AuNP‐collagen hydrogels and either primary or human induced pluripotent stem cell (hiPSC)‐derived cardiomyocytes show enhanced beating properties. hiPSC‐derived cardiomyocytes exhibit more aligned and wider sarcomeres in bPEI‐AuNP‐collagen hydrogels compared to collagen hydrogels. Furthermore, the presence of bPEI‐AuNPs result in advanced electrical coupling evidenced by synchronous and homogenous calcium flux throughout the tissue. RNA‐seq analyses are in agreement with these observations. Collectively, this data demonstrate the potential of bPEI‐AuNP‐collagen hydrogels to improve tissue engineering approaches to prevent heart failure and possibly treat diseases of other electrically sensitive tissues.
Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher-level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 μm wide microfluidic channel. The fluid shear stress induces large, near ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks.
This study aimed to develop three-dimensional (3D)-printed hydrogels containing phytotherapeutic agents as multifunctional wound dressings. In this regard, 3D-printed sodium alginate (ALG)−xanthan gum (XAN) hydrogels incorporated with different clove essential oil (CLV) concentrations were produced by the extrusion-based 3D-printing technology. Rheology measurements, filament fusion, and filament collapse analyses indicated that XAN's blending overcame the challenges associated with ALG's printability and shape fidelity. Attenuated total reflection-Fourier-transform infrared (ATR-FTIR) spectra and total phenolic content assay confirmed the presence of CLV in the 3D-printed hydrogels. Additionally, the releasing profile showed that CLV exhibited long-term release for up to 28 days. Furthermore, the incorporation of CLV increased 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging while reducing the S. aureus and E. coli relative bacterial viability; thereby, the CLV incorporation enhanced the 3Dprinted ALG−XAN hydrogel antioxidant and antibacterial activity. In addition, anti-inflammatory activity was assessed using Raw 264.7 macrophage-like cells, and the results demonstrated that CLV reduced nitric oxide (NO) concentration in medium, indicating a potential anti-inflammatory effect. Moreover, in vitro cytotoxicity results showed that the incorporation of CLV has no toxic effect on NHDF cells, whereas the proliferation of NHDF cells exhibited a dose-dependent response. In conclusion, the present study shows not only the development of a new ALG-XAN biomaterial ink but also the potential benefit of natural phytotherapeutics incorporated into 3D-printed hydrogels as a multifunctional wound dressing.
are easily modeled. For a heterodimer such as ab-tropomyosin, there are multiple ways the b-chain could be incorporated into the coiled-coil structure each having different predicted contacts between the b-chain and actin. In this study, we expand our thin filament modeling to include ab-tropomyosin. The b-chain is incorporated in the model by first homology modeling the side chains and then considering multiple ways to form the heterodimers (substituting different a-chains with b-chains). These models were then subjected to molecular dynamics simulation as isolated dimers, a pair of head-to-tail linked dimers, and as part of an infinite thin filament cable. The results of the simulations show that there may be a preferred way to incorporate the b-chain into the tropomyosin coiled-coil. Therefore in the cell, there may only be a single conformer of ab-tropomyosin on the thin filament.
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