Development of bioactive short fiber-reinforced printable hydrogels with tunable mechanical and osteogenic properties for bone repair.

Personalized bone-regenerative materials have attracted substantial interest in recent years. Modern clinical settings demand the use of engineered materials incorporating patient-derived cells, cytokines, antibodies, and biomarkers to enhance the process of regeneration. In this work, we formulated short microfiber-reinforced hydrogels with platelet-rich fibrin (PRF) to engineer implantable multi-material core-shell bone grafts. By employing 3D bioprinting technology, we fabricated a core-shell bone graft from a hybrid composite hydroxyapatite-coated poly(lactic acid) (PLA) fiber-reinforced methacryolyl gelatin (GelMA)/alginate hydrogel. The overall concept involves 3D bioprinting of long bone mimic microstructures that resemble a core-shell cancellous-cortical structure, with a stiffer shell and a softer core with our engineered biomaterial. We observed a significantly enhanced stiffness in the hydrogel scaffold incorporated with hydroxyapatite (HA)-coated PLA microfibers compared to the pristine hydrogel construct. Furthermore, HA non-coated PLA microfibers were mixed with PRF and GelMA/alginate hydrogel to introduce a slow release of growth factors which can further enhance cell maturation and differentiation. These patient-specific bone grafts deliver cytokines and growth factors with distinct spatiotemporal release profiles to enhance tissue regeneration. The biocompatible and bio-responsive bone mimetic core-shell multi-material structures enhance osteogenesis and can be customized to have materials at a specific location, geometry, and material combination.

New dimensions of electrospun nanofiber material designs for biotechnological uses.

Electrospinning technology has garnered wide attention over the past few decades in various biomedical applications including drug delivery, cell therapy, and tissue engineering. This technology can create nanofibers with tunable fiber diameters and functionalities. However, the 2D membrane nature of the nanofibers, as well as the rigidity and low porosity of electrospun fibers, lower their efficacy in tissue repair and regeneration. Recently, new avenues have been explored to resolve the challenges associated with 2D electrospun nanofiber membranes. This review discusses recent trends in creating different electrospun nanofiber microstructures from 2D nanofiber membranes by using various post-processing methods, as well as their biotechnological applications.

Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model.

Cancer treatment resistance is a caused by presence of various types of cells and heterogeneity within the tumor. Tumor cell-cell and cell-microenvironment interactions play a significant role in the tumor progression and invasion, which have important implications for diagnosis, and resistance to chemotherapy. In this study, we develop 3D bioprinted in vitro models of the breast cancer tumor microenvironment made of co-cultured cells distributed in a hydrogel matrix with controlled architecture to model tumor heterogeneity. We hypothesize that the tumor could be represented by a cancer cell-laden co-culture hydrogel construct, whereas its microenvironment can be modeled in a microfluidic chip capable of producing a chemical gradient. Breast cancer cells (MCF7 and MDA-MB-231) and non-tumorigenic mammary epithelial cells (MCF10A) were embedded in the alginate-gelatine hydrogels and printed using a multi-cartridge extrusion bioprinter. Our approach allows for precise control over position and arrangements of cells in a co-culture system, enabling the design of various tumor architectures. We created samples with two different types of cells at specific initial locations, where the density of each cell type was carefully controlled. The cells were either randomly mixed or positioned in sequential layers to create cellular heterogeneity. To study cell migration toward chemoattractant, we developed a chemical microenvironment in a chamber with a gradual chemical gradient. As a proof of concept, we studied different migration patterns of MDA-MB-231 cells toward the epithelial growth factor gradient in presence of MCF10A cells in different ratios using this device. Our approach involves the integration of 3D bioprinting and microfluidic devices to create diverse tumor architectures that are representative of those found in various patients. This provides an excellent tool for studying the behavior of cancer cells with high spatial and temporal resolution.

Predicting and elucidating the post-printing behavior of 3D printed cancer cells in hydrogel structures by integrating in-vitro and in-silico experiments.

A key feature distinguishing 3D bioprinting from other 3D cell culture techniques is its precise control over created structures. This property allows for the high-resolution fabrication of biomimetic structures with controlled structural and mechanical properties such as porosity, permeability, and stiffness. However, analyzing post-printing cellular dynamics and optimizing their functions within the 3D fabricated environment is only possible through trial and error and replicating several experiments. This issue motivated the development of a cellular automata model for the first time to simulate post-printing cell behaviour within the 3D bioprinted construct. To improve our model, we bioprinted a 3D construct using MDA-MB-231 cell-laden hydrogel and evaluated cellular functions, including viability and proliferation in 11 days. The results showed that our model successfully simulated the 3D bioprinted structure and captured in-vitro observations. We demonstrated that in-silico model could predict and elucidate post-printing biological functions for different initial cell numbers in bioink and different bioink formulations with gelatine and alginate, without replicating several costly and time-consuming in-vitro measurements. We believe such a computational framework will substantially impact 3D bioprinting's future application. We hope this study inspires researchers to further realize how an in-silico model might be utilized to advance in-vitro 3D bioprinting research.

Surface-Mediated Hydrogen Bonding of Proteinogenic α-Amino Acids on Silicon.

Understanding the adsorption, film growth mechanisms, and hydrogen bonding interactions of biological molecules on semiconductor surfaces has attracted much recent attention because of their applications in biosensors, biocompatible materials, and biomolecule-based electronic devices. One of the most challenging questions when studying the behavior of biomolecules on a metal or semiconductor surface is "What are the driving forces and film growth mechanisms for biomolecular adsorption on these surfaces?" Despite a large volume of work on self-assembly of amino acids on single-crystal metal surfaces, semiconductor surfaces offer more direct surface-mediated interactions and processes with biomolecules. This is due to their directional surface dangling bonds that could significantly perturb hydrogen bonding arrangements. For all the proteinogenic biomolecules studied to date, our group has observed that they generally follow a "universal" three-stage growth process on Si(111)7×7 surface. This is supported by corroborating data obtained from a three-pronged approach of combining chemical-state information provided by X-ray photoelectron spectroscopy (XPS) and the site-specific local density-of-state images obtained by scanning tunneling microscopy (STM) with large-scale quantum mechanical modeling based on the density functional theory with van der Waals corrections (DFT-D2). Indeed, this three-stage growth process on the 7×7 surface has been observed for small benchmark biomolecules, including glycine (the simplest nonchiral amino acid), alanine (the simplest chiral amino acid), cysteine (the smallest amino acid with a thiol group), and glycylglycine (the smallest (di)peptide of glycine). Its universality is further validated here for the other sulfur-containing proteinogenic amino acid, methionine. We use methionine as an example of prototypical proteinogenic amino acids to illustrate this surface-mediated process. This type of growth begins with the formation of a covalent-bond driven interfacial layer (first adlayer), followed by that of a transitional layer driven by interlayer and intralayer hydrogen bonding (second adlayer), and then finally the zwitterionic multilayers (with intralayer hydrogen bonding). The important role of surface-mediated hydrogen bonding as the key for this universal three-stage growth process is demonstrated. This finding provides new insight into biomolecule-semiconductor surface interactions often found in biosensors and biomolecular electronic devices. We also establish the trends in the H-bond length among different types of the hydrogen bonding for dimolecular structures in the gas phase and on the Si(111)7×7 surface, the latter of which could be validated by their STM images. Finally, five simple rules of thumb are developed to summarize the adsorption properties of these proteinogenic biomolecules as mediated by hydrogen bonding, and they are expected to provide a helpful guide to future studies of larger biomolecules and their potential applications.

Plasmonic gold nanoparticles for ZnO-nanotube photoanodes in dye-sensitized solar cell application.

Surface modification of nanostructured metal oxides with metal nanoparticles has been extensively used to enhance their nanoscale properties. The unique properties of metal nanoparticles associated with their controllable dimensions allow these metal nanoparticles to be precisely engineered for many applications, particularly for renewable energy. Here, a simple electrodeposition method to synthesize gold nanoparticles (GNPs) on electrochemically grown ZnO nanotubes (NTs) is reported. The size distribution and areal density of the GNPs can be easily controlled by manipulating the concentration of AuCl3 electrolyte solution, and the deposition time, respectively. An excellent enhancement in the optical properties of ZnO NTs surface-decorated with GNPs (GNP/ZnO-NT), especially in the visible region, is attributed to their surface plasmon resonance. The plasmonic effects of GNPs, together with the large specific surface area of ZnO NTs, can be used to significantly enhance the dye-sensitized solar cell (DSSC) properties. Furthermore, the Schottky barrier at the Au/ZnO interface could prevent electron back transfer from the conduction band of ZnO to the redox electrolyte and thus could substantially increase electron injection in the ZnO conduction band, which would further improve the overall performance of the constructed DSSCs. The GNP/ZnO-NT photoanode has been found to increase the efficiency of the DSSC significantly to 6.0% from 4.7% of the pristine ZnO-NT photoanode, together with corresponding enhancements in short-circuit current density from 10.4 to 13.1 mA cm(-2) and in fill factor from 0.60 to 0.75, while the open-circuit voltage remain effectively unchanged (from 0.60 to 0.61 V). Surface decoration with GNPs therefore provides an effective approach to creating not only a high specific surface area for superior loading of dye molecules, but also higher absorbance capability due to their plasmonic effect, all of which lead to excellent performance enhancement for DSSC application.

Bimetallic nanoparticles for arsenic detection.

Effective and sensitive monitoring of heavy metal ions, particularly arsenic, in drinking water is very important to risk management of public health. Arsenic is one of the most serious natural pollutants in soil and water in more than 70 countries in the world. The need for very sensitive sensors to detect ultralow amounts of arsenic has attracted great research interest. Here, bimetallic FePt, FeAu, FePd, and AuPt nanoparticles (NPs) are electrochemically deposited on the Si(100) substrate, and their electrochemical properties are studied for As(III) detection. We show that trace amounts of As(III) in neutral pH could be determined by using anodic stripping voltammetry. The synergistic effect of alloying with Fe leads to better performance for Fe-noble metal NPs (Au, Pt, and Pd) than pristine noble metal NPs (without Fe alloying). Limit of detection and linear range are obtained for FePt, FeAu, and FePd NPs. The best performance is found for FePt NPs with a limit of detection of 0.8 ppb and a sensitivity of 0.42 µA ppb(-1). The selectivity of the sensor has also been tested in the presence of a large amount of Cu(II), as the most detrimental interferer ion for As detection. The bimetallic NPs therefore promise to be an effective, high-performance electrochemical sensor for the detection of ultratrace quantities of arsenic.

Reversible structural transformation and enhanced performance of PEDOT:PSS-based hybrid solar cells driven by light intensity.

Hybrid solar cells made of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) and appropriate amounts of a cosolvent and a fluorosurfactant on planar n-type silicon substrates showed a photoconversion efficiency (PCE) of above 13%. These cells also exhibited stable, reproducible, and high external quantum efficiency (EQE) that was not sensitive to light-bias intensity (LBI). In contrast, solar cells made of pristine PEDOT: PSS showed low PCE and high EQE only under certain measurement conditions. The EQE was found to degrade with increasing LBI. Here we report that the LBI-sensitive variation of EQE of the low-PCE cells is related to a reversible structural transformation from a quinoid to a benzoid structure of PEDOT.

In situ hybridization of superparamagnetic iron-biomolecule nanoparticles.

The increase in interest in the integration of organic-inorganic nanostructures in recent years has promoted the use of hybrid nanoparticles (HNPs) in medicine, energy conversion, and other applications. Conventional hybridization methods are, however, often long, complicated, and multistepped, and they involve biomolecules and discrete nanostructures as separate entities, all of which hinder the practical use of the resulting HNPs. Here, we present a novel, in situ approach to synthesizing size-specific HNPs using Fe-biomolecule complexes as the building blocks. We choose an anticancer peptide (p53p, MW 1.8 kDa) and an enzyme (GOx, MW 160 kDa) as model molecules to demonstrate the versatility of the method toward different types of molecules over a large size range. We show that electrostatic interaction for complex formation of metal hydroxide ion with the partially charged side of biomolecule in the solution is the key to hybridization of metal-biomolecule materials. Electrochemical deposition is then used to produce hybrid NPs from these complexes. These HNPs with controllable sizes ranging from 30 nm to 3.5 µm are found to exhibit superparamagnetic behavior, which is a big challenge for particles in this size regime. As an example of greatly improved properties and functionality of the new hybrid material, in vitro toxicity assessment of Fe-GOx HNPs shows no adverse effect, and the Fe-p53p HNPs are found to selectively bind to cancer cells. The superparamagnetic nature of these HNPs (superparamagnetic even above the size regime of 15-20 nm!), their biocompatibility, and the direct integration approach are fundamentally important to biomineralization and general synthesis strategy for bioinspired functional materials.

Bimetallic FeNi concave nanocubes and nanocages.

Concave nanostructures are rare because of their thermodynamically unfavorable shapes. We prepared bimetallic FeNi concave nanocubes with high Miller index planes through controlled triggering of the different growth kinetics of Fe and Ni. Taking advantage of the higher activity of the high-index planes, we then fabricated monodispersed concave nanocages via a material-independent electroleaching process. With the high-index facets exposed, these concave nanocubes and nanocages are 10- and 100-fold more active, respectively, toward electrodetection of 4-aminophenol than cuboctahedrons, providing a label-free sensing approach for monitoring toxins in water and pharmaceutical wastes.

FePt alloy nanoparticles for biosensing: enhancement of vitamin C sensor performance and selectivity by nanoalloying.

Electrocatalytic activity of supported FePt alloy nanoparticles (NPs) with different compositions (Fe25Pt75, Fe30Pt70, Fe35Pt65) for the electro-oxidation of vitamin C is investigated. These spherical FePt NPs with nanocrystallite size of 7-9 nm are found to consist of a nanoalloy core with a more Pt-rich shell. The FePt alloy NPs are superior catalysts than Pt NPs for vitamin C electro-oxidation, with a linear concentration range of 0.01-1 mM, a high sensitivity of 4.347 mA cm(-2) mM(-1), and a low detection limit of 0.1 µM (S/N = 3). By effectively reducing the overpotential for the electro-oxidation, these alloy NPs are significantly more selective to the detection of vitamin C against other common interference species, including dopamine, citric acid, uric acid, glucose, and NaCl. Enhancement in sensor performance can be attributed to the increase in surface area due to reduction of nanocrystallite size and to modification in the Pt electronic structure as a result of nanoalloying. These are supported by the X-ray diffraction data and binding energy shifts as observed by X-ray photoelectron spectroscopy, respectively. Alloying therefore represents a powerful approach to introduce synergetic properties for new biosensor applications.