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A hierarchical nanocomposite of carbon microspheres decorated with tungsten oxide (WO₃) nanocrystals resulted from the hydrothermal treatment of a precursor solution containing glucose and tungstic acid. The dehydration of glucose molecules formed oligosaccharides, which consequently carbonized, turning into carbon microspheres. The carbon microspheres then acted as a spherical nucleus onto which WO₃nanocrystals grew via heterogeneous nucleation. The reaction product showed a phase junction of orthorhombic and monoclinic WO_3,which transitioned to mix-phase of tetragonal and monoclinic WO₃after a subsequent heat treatment at 600 °C in an inert condition. The electrochemical tests showed that incorporating WO₃onto the carbon (WO₃/C) resulted in a three-fold increase in the specific capacitance compared to WO₃alone and a high coulombic and energy efficiencies of 98.2% and 92.8%, respectively. The nanocomposite exhibited supercapacitance with both Faradaic and non-Faradaic charge storage mechanisms. Electrochemical impedance spectroscopy showed a lower charge transfer resistance for the composite at R_ct = 11.7Ω.

 

Microneedles are micron-sized devices that are used for the transdermal administration of a wide range of active pharmaceutics substances with minimally invasive pain. In the past decade, various additive manufacturing technologies have been used for the fabrication of microneedles; however, they have limitations due to material compatibility and bioavailability and are time-consuming and expensive processes. Additive manufacturing (AM), which is popularly known as 3D-printing, is an innovative technology that builds three-dimensional solid objects (3D). This article provides a comprehensive review of the different 3D-printing technologies that have the potential to revolutionize the manufacturing of microneedles. The application of 3D-printed microneedles in various fields, such as drug delivery, vaccine delivery, cosmetics, therapy, tissue engineering, and diagnostics, are presented. This review also enumerates the challenges that are posed by the 3D-printing technologies, including the manufacturing cost, which limits its viability for large-scale production, the compatibility of the microneedle-based materials with human cells, and concerns around the efficient administration of large dosages of loaded microneedles. Furthermore, the optimization of microneedle design parameters and features for the best printing outcomes is of paramount interest. The Food and Drug Administration (FDA) regulatory guidelines relating to the safe use of microneedle devices are outlined. Finally, this review delineates the implementation of futuristic technologies, such as artificial intelligence algorithms, for 3D-printed microneedles and 4D-printing capabilities. 

Three-dimensional (3D) printing is implemented for surface modification of titanium alloy substrates with multilayered biofunctional polymeric coatings. Poly(lactic-coglycolic) acid (PLGA) and polycaprolactone (PCL) polymers were embedded with amorphous calcium phosphate (ACP) and vancomycin (VA) therapeutic agents to promote osseointegration and antibacterial activity, respectively. PCL coatings revealed a uniform deposition pattern of the ACP-laden formulation and enhanced cell adhesion on the titanium alloy substrates as compared to the PLGA coatings. Scanning electron microscopy and Fourier-transform infrared spectroscopy confirmed a nanocomposite structure of ACP particles showing strong binding with the polymers. Cell viability data showed comparable MC3T3 osteoblast proliferation on polymeric coatings as equivalent to positive controls. In vitro live/dead assessment indicated higher cell attachments for 10 layers (burst release of ACP) as compared to 20 layers (steady release) for PCL coatings. The PCL coatings loaded with the antibacterial drug VA displayed a tunable release kinetics profile based on the multilayered design and drug content of the coatings. Moreover, the concentration of active VA released from the coatings was above the minimum inhibitory concentration and minimum bactericidal concentration, demonstrating its effectiveness against Staphylococcus aureus bacterial strain. This research provides a basis for developing antibacterial biocompatible coatings to promote osseointegration of orthopedic implants. 

The development of Cyber-Physical Systems (CPS) and the Internet of Things (IoT) has influenced Cyber-Physical Manufacturing Systems (CPMS). Collaborative manufacturing among organizations with geographically distributed operations using Nanomanufacturing (NM) requires integrated networking for enhanced productivity. The present research provides a unique cyber nanomanufacturing framework by combining digital design with various artificial neural networks (ANN) approaches to predict the optimal nano/micro-manufacturing process. It enables the visualization tool for real-time allocation of nano/micro-manufacturing resources to simulate machine availability for five types of NM processes in real-time for a dynamic machine identification system. This research establishes a foundation for a smart agent system with predictive capabilities for cyber nanomanufacturing in real-time. 

The interaction between bone morphogenetic protein-2 (BMP-2) and the surface of biomaterials is essential for the restoration of bone and cartilage tissue, inducing cellular differentiation and proliferation. The properties of the surface, including topology features, regulate the conformation and bioactivity of the protein. In this research, we investigated the influence of nanopatterned surfaces on the interaction of a homodimer BMP-2 with graphite material by combining molecular dynamics (MD) and steered molecular dynamics (SMD) simulations. The graphite substrates were patterned as flat, linear grating, square, and circular profiles in combination with BMP-2 conformation in the side-on configuration. Ramachandran plots for the wrist and knuckle epitopes indicated no steric hindrances and provided binding sites to type I and type II receptors. Results showed two optimal patterns that increased protein adsorption of the lower monomer while preserving the secondary structure and leaving the upper monomer free to interact with the cells. Charged residues arginine and lysine and polar residues histidine and tyrosine were the main residues responsible for the strong interaction with the graphite surface. This research provides new molecular-level insights to further understand the mechanisms underlying protein adsorption on nanoscale patterned substrates. 

Nanoscale surface topographies mediated with biochemical cues influence the differentiation of stem cells into different lineages. This research focuses on the adsorption behavior of bone morphogenetic protein (BMP-2) on nanopatterned gold substrates, which can aid in the differentiation of bone and cartilage tissue constructs. The gold substrates were patterned as flat, pillar, linear grating, and linear-grating deep based, and the BMP-2 conformation in end-on configuration was studied over 20 ns. The linear grating deep substrate pattern had the highest adsorption energy of around 125 kJ/mol and maintained its radius of gyration of 18.5 Å, indicating a stable adsorption behavior. Secondary structures including α-helix and β-sheet displayed no denaturation, and thus, the bioavailability of the BMP-2, for the deep linear-grating pattern. Ramachandran plots for the wrist and knuckle epitopes indicated no steric hindrances and provided binding sites to type I and type II receptors. The deep linear-grating substrate had the highest number of contacts (88 atoms) within 5 Å of the gold substrate, indicating its preferred nanoscale pattern choice among the substrates considered. This research provides new insights into the atomistic adsorption of BMP-2 on nanoscale topographies of a gold substrate, with applications in biomedical implants and regenerative medicine. 

Drug delivery through the skin offers many advantages such as avoidance of hepatic first-pass metabolism, maintenance of steady plasma concentration, safety, and compliance over oral or parenteral pathways. However, the biggest challenge for transdermal delivery is that only a limited number of potent drugs with ideal physicochemical properties can passively diffuse and intercellularly permeate through skin barriers and achieve therapeutic concentration by this route. Significant efforts have been made toward the development of approaches to enhance transdermal permeation of the drugs. Among them, microneedles represent one of the microscale physical enhancement methods that greatly expand the spectrum of drugs for transdermal and intradermal delivery. Microneedles typically measure 0.1–1 mm in length. In this review, microneedle materials, fabrication routes, characterization techniques, and applications for transdermal delivery are discussed. A variety of materials such as silicon, stainless steel, and polymers have been used to fabricate solid, coated, hollow, or dissolvable microneedles. Their implications for transdermal drug delivery have been discussed extensively. However, there remain challenges with sustained delivery, efficacy, cost-effective fabrication, and large-scale manufacturing. This review discusses different modes of characterization and the gaps in manufacturing technologies associated with microneedles. This review also discusses their potential impact on drug delivery, vaccine delivery, disease diagnostic, and cosmetics applications.