Multicomponent Hydrogels for the Formation of Vascularized Bone-like Constructs In Vitro.

The native extracellular matrix (ECM) is a complex gel-like system with a broad range of structural features and biomolecular signals. Hydrogel platforms that can recapitulate the complexity and signaling properties of this ECM would have enormous impact in fields ranging from tissue engineering to drug discovery. Here, we report on the design, synthesis, and proof-of-concept validation of a microporous and nanofibrous hydrogel exhibiting multiple bioactive epitopes designed to recreate key features of the bone ECM. The material platform integrates self-assembly with orthogonal enzymatic cross-linking to create a supramolecular environment comprising hyaluronic acid modified with tyramine (HA-Tyr) and peptides amphiphiles (PAs) designed to promote cell adhesion (RGDS-PA), osteogenesis (Osteo-PA), and angiogenesis (Angio-PA). Through individual and co-cultures of human adipose derived mesenchymal stem cells (hAMSCs) and human umbilical vascular endothelial cells (HUVECs), we confirmed the capacity of the HA-Tyr/RGDS-PA/Osteo-PA/Angio-PA hydrogel to promote cell adhesion as well as osteogenic and angiogenic differentiation in both 2D and 3D setups. Furthermore, using immunofluorescent staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), we demonstrated co-differentiation and organization of hAMSCs and HUVECs into 3D aggregates resembling vascularized bone-like constructs

A thermosensitive electromechanical model for detecting biological particles

Miniature electromechanical systems form a class of bioMEMS that can provide appropriate sensitivity. In this research, a thermo-electro-mechanical model is presented to detect biological particles in the microscale. Identification in the model is based on analyzing pull-in instability parameters and frequency shifts. Here, governing equations are derived via the extended Hamilton’s principle. The coupled effects of system parameters such as surface layer energy, electric field correction, and material properties are incorporated in this thermosensitive model. Afterward, the accuracy of the present model and obtained results are validated with experimental, analytical, and numerical data for several cases. Performing a parametric study reveals that mechanical properties of biosensors can significantly affect the detection sensitivity of actuated ultra-small detectors and should be taken into account. Furthermore, it is shown that the number or dimension of deposited particles on the sensing zone can be estimated by investigating the changes in the threshold voltage, electrode deflection, and frequency shifts. The present analysis is likely to provide pertinent guidelines to design thermal switches and miniature detectors with the desired performance. The developed biosensor is more appropriate to detect and characterize viruses in samples with different temperatures

De Novo Design of Functional Coassembling Organic–Inorganic Hydrogels for Hierarchical Mineralization and Neovascularization

Synthetic nanostructured materials incorporating both organic and inorganic components offer a unique, powerful, and versatile class of materials for widespread applications due to the distinct, yet complementary, nature of the intrinsic properties of the different constituents. We report a supramolecular system based on synthetic nanoclay (Laponite, Lap) and peptide amphiphiles (PAs, PAH3) rationally designed to coassemble into nanostructured hydrogels with high structural integrity and a spectrum of bioactivities. Spectroscopic and scattering techniques and molecular dynamic simulation approaches were harnessed to confirm that PAH3 nanofibers electrostatically adsorbed and conformed to the surface of Lap nanodisks. Electron and atomic force microscopies also confirmed an increase in diameter and surface area of PAH3 nanofibers after coassembly with Lap. Dynamic oscillatory rheology revealed that the co-assembled PAH3-Lap hydrogels displayed high stiffness and robust self-healing behavior while gas adsorption analysis confirmed a hierarchical and heterogeneous porosity. Furthermore, this distinctive structure within the three-dimensional (3D) matrix provided spatial confinement for the nucleation and hierarchical organization of high-aspect ratio hydroxyapatite nanorods into well-defined spherical clusters within the 3D matrix. Applicability of the organic-inorganic PAH3-Lap hydrogels was assessed in vitro using human bone marrow-derived stromal cells (hBMSCs) and ex vivo using a chick chorioallantoic membrane (CAM) assay. The results demonstrated that the organic-inorganic PAH3-Lap hydrogels promote human skeletal cell proliferation and, upon mineralization, integrate with the CAM, are infiltrated by blood vessels, stimulate extracellular matrix production, and facilitate extensive mineral deposition relative to the controls

Xenogenic neural stem cell-derived extracellular nanovesicles modulate human mesenchymal stem cell fate and reconstruct metabolomic structure

Abstract Extracellular nanovesicles, particularly exosomes, can deliver their diverse bioactive biomolecular content, including miRNAs, proteins, and lipids, thus providing a context for investigating the capability of exosomes to induce stem cells toward lineage-specific cells and tissue regeneration. In this study, it is demonstrated that rat subventricular zone neural stem cell-derived exosomes (rSVZ-NSCExo) can control neural-lineage specification of human mesenchymal stem cells (hMSCs). Microarray analysis shows that the miRNA content of rSVZ-NSCExo is a faithful representation of rSVZ tissue. Through immunocytochemistry, gene expression, and multi-omics analyses, the capability to use rSVZ-NSCExo to induce hMSCs into a neuroglial or neural stem cell phenotype and genotype in a temporal and dose-dependent manner via multiple signaling pathways is demonstrated. The current study presents a new and innovative strategy to modulate hMSCs fate by harnessing the molecular content of exosomes, thus suggesting future opportunities for rSVZ-NSCExo in nerve tissue regeneration

Electrochemical Impedance Analysis of Biofunctionalized Conducting Polymer-Modified Graphene-CNTs Nanocomposite for Protein Detection

We report an electrodeposited poly(pyrrole-co-pyrrolepropylic acid) copolymer modified electroactive graphene-carbon nanotubes composite deposited on a glassy carbon electrode to detect the protein antigen (cTnI). The copolymer provides pendant carboxyl groups for the site-specific covalent immobilization of protein antibody, anti-troponin I. The hybrid nanocomposite was used as a transducer for biointerfacial impedance sensing for cTnI detection. The results show that the hybrid exhibits a pseudo capacitive behaviour with a maximum phase angle of 49 degrees near 1 Hz, which is due to the inhomogeneous and porous structure of the hybrid composition. The constant phase element of copolymer is 0.61 (n = 0.61), whereas, it is 0.88 (n = 0.88) for the hybrid composites, indicating a comparatively homogeneous microstructure after biomolecular functionalization. The transducer shows a linear change in charge transfer characteristic (R-et) on cTnI immunoreaction for spiked human serum in the concentration range of 1.0 pg mL(-1) - 10.0 ng mL(-1). The sensitivity of the transducer is 167.8 +/- 14.2 Omega cm(2) per decade, and it also exhibits high specificity and good reproducibility

Sophisticated Biocomposite Scaffolds from Renewable Biomaterials for Bone Tissue Engineering

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