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Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a delivery vehicle which promotes desired cell behavior for new bone formation. In this work, we describe the use of an injectable microporous hydrogel, made of crosslinked gelatin microgels, for the encapsulation and delivery of human mesenchymal stem cells (MSCs) and compared it to a traditional nonporous injectable hydrogel. MSCs encapsulated in the microporous hydrogel showed rapid cell spreading with direct cell–cell connections whereas the MSCs in the nonporous hydrogel were entrapped by the surrounding polymer mesh and isolated from each other. On a per-cell basis, encapsulation in microporous hydrogel induced a 4 × increase in alkaline phosphatase (ALP) activity and calcium mineral deposition in comparison to nonporous hydrogel, as measured by ALP and calcium assays, which indicates more robust osteogenic differentiation. RNA-seq confirmed the upregulation of the genes and pathways that are associated with cell spreading and cell–cell connections, as well as the osteogenesis in the microporous hydrogel. These results demonstrate that microgel-based injectable hydrogels can be useful tools for therapeutic cell delivery for bone tissue repair.

Incremental sheet metal forming is known for its high flexibility, making it suitable for fabricating low-batch, highly customized complex parts. In this article, a localized multipass toolpath referred to as localized reforming, with reverse forming in a region of interest, is employed within the double-sided incremental forming (DSIF) process to manipulate the mechanical properties of a truncated pyramid formed from austenitic stainless steel sheet, SS304, through deformation-induced martensite transformation. DSIF forms a clamped sheet through localized deformations by two opposing tools. The toolpath effect in localized reforming is examined in terms of martensite transformation, geometrical accuracy, and thickness distribution. The results are compared with a conventional toolpath, i.e., forming in a single pass. The results show that varying toolpaths lead to different martensite transformation levels, while final geometry and thickness remain similar. The study demonstrates that localized reforming significantly increases martensite transformation in the specified region, i.e., the center of the pyramid wall, to ∼70%, with a martensite fraction remaining around 25% elsewhere. In comparison, using a single pass forming toolpath leads to a decreasing martensite fraction from the base of the pyramid toward the apex, due to the heat generated, with values <10% along the entire wall. Through finite element simulation, it is shown that the increase in martensite transformation of the region of interest is with the plastic deformation accumulation during the reverse pass. These findings highlight the potential to tailor mechanical properties in specific areas using a reforming toolpath in DSIF.

Current research practice for optimizing bioink involves exhaustive experimentation with multi-material composition for determining the printability, shape fidelity and biocompatibility. Predicting bioink properties can be beneficial to the research community but is a challenging task due to the non-Newtonian behavior in complex composition. Existing models such as Cross model become inadequate for predicting the viscosity for heterogeneous composition of bioinks. In this paper, we utilize a machine learning framework to accurately predict the viscosity of heterogeneous bioink compositions, aiming to enhance extrusion-based bioprinting techniques. Utilizing Bayesian optimization (BO), our strategy leverages a limited dataset to inform our model. This is a technique especially useful of the typically sparse data in this domain. Moreover, we have also developed a mask technique that can handle complex constraints, informed by domain expertise, to define the feasible parameter space for the components of the bioink and their interactions. Our proposed method is focused on predicting the intrinsic factor (e.g. viscosity) of the bioink precursor which is tied to the extrinsic property (e.g. cell viability) through the mask function. Through the optimization of the hyperparameter, we strike a balance between exploration of new possibilities and exploitation of known data, a balance crucial for refining our acquisition function. This function then guides the selection of subsequent sampling points within the defined viable space and the process continues until convergence is achieved, indicating that the model has sufficiently explored the parameter space and identified the optimal or near-optimal solutions. Employing this AI-guided BO framework, we have developed, tested, and validated a surrogate model for determining the viscosity of heterogeneous bioink compositions. This data-driven approach significantly reduces the experimental workload required to identify bioink compositions conducive to functional tissue growth. It not only streamlines the process of finding the optimal bioink compositions from a vast array of heterogeneous options but also offers a promising avenue for accelerating advancements in tissue engineering by minimizing the need for extensive experimental trials.

DNA serves as a model system in polymer physics due to its ability to be obtained as a uniform polymer with controllable topology and non‐equilibrium behavior. Currently, a major obstacle in the widespread adoption of DNA is obtaining it on a scale and cost basis that accommodates bulk rheology and high‐throughput screening. To address this, recent advancements in bioreactor‐based plasmid DNA production is coupled with anion exchange chromatography to produce a unified approach to generating gram‐scale quantities of monodisperse DNA. With this method, 1.1 grams of DNA is obtained per batch to generate solutions with concentrations up to 116 mg mL⁻¹of uniform supercoiled and relaxed circular plasmid DNA, which is roughly 69 times greater than the overlap concentration. The utility of this method is demonstrated by performing bulk rheology measurements on DNA of different length, topologies, and concentrations at sample volumes up to 1 mL. The measured elastic moduli are orders of magnitude larger than those previously reported for DNA and allowed for the construction of a time‐concentration superposition curve that spans twelve decades of frequency. Ultimately, these results could provide important insights into the dynamics of ring polymers and the nature of highly condensed DNA dynamics.

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Single point incremental forming (SPIF) is a flexible manufacturing process that has applications in industries ranging from biomedical to automotive. In addition to rapid prototyping, which requires easy adaptations in geometry or material for design changes, control of the final part properties is desired. One strategy that can be implemented is stress superposition, which is the application of additional stresses during an existing manufacturing process. Tensile and compressive stresses applied during SPIF showed significant effects on the resulting microstructure in stainless steel 304 truncated square pyramids. Specifically, the amount of martensitic transformation was increased through stress superposed incremental forming. Finite element analyses with advanced material modeling supported that the stress triaxiality had a larger effect than the Lode angle parameter on the phase transformation that occurred during deformation. By controlling the amount of tensile and compressive stresses superposed during incremental forming, the microstructure of the final component can be manipulated based on the intended application and desired final part properties.

Controlled modulation of electronic and magnetic properties in stimuli‐responsive materials provides valuable insights for the design of magnetoelectric or multiferroic devices. This paper demonstrates the modulation of electrical and magnetic properties of a semiconductive, paramagnetic metal−organic framework (MOF) Cu₃(C₆O₆)₂with small gaseous molecules, NH₃, H₂S, and NO. This study merges chemiresistive and magnetic tests to reveal that the MOF undergoes simultaneous changes in electrical conductance and magnetization that are uniquely modulated by each gas. The features of response, including direction, magnitude, and kinetics, are modulated by the physicochemical properties of the gaseous molecules. This study advances the design of multifunctional materials capable of undergoing simultaneous changes in electrical and magnetic properties in response to chemical stimuli.

Sepsis, whole‐body inflammation caused by the contamination of blood by bacteria and endotoxins, affects millions of patients annually with high mortality rates. A recent promising approach to treat sepsis involves the removal of bacteria and endotoxins using extracorporeal blood‐cleansing devices. However, poor specificity, slow recognition of pathogens, and high costs remain the main limitations. Here, the melanin, a biologically derived pigment, is reported for the rapid binding of bacteria and endotoxins from the contaminated blood . This novel approach utilizes the specific binding between Zn²⁺‐loaded melanin and bacteria/endotoxins with minimal nonspecific interactions with human blood components. Melanin contains various chemical functional groups that allow reversible chelation of metallic ions such as Zn²⁺via redox reactions. Zn²⁺enables rapid and specific binding with bacteria/endotoxins due to the strong electrostatic interactions between Zn²⁺and phosphate ions. The presence of various zinc‐binding proteins on the bacterial cell membrane further enhances the binding. The well‐known biocompatibility and low cost make melanin an ideal material to interface with human blood. Zn²⁺‐charged melanin can remove 90% ofE. coliand 100% of endotoxin in PBS and human blood. Zn²⁺‐melanin also demonstrated excellent hemocompatibility shown by protein adsorption, blood coagulation, and hemolysis tests.

3D continuous mesoscale architectures of nanomaterials possess the potential to revolutionize real‐time electrochemical biosensing through higher active site density and improved accessibility for cell proliferation. Herein, 3D microporous Ti₃C₂T_XMXene biosensors are fabricated to monitor antibiotic release in tissue engineering scaffolds. The Ti₃C₂T_X‐coated 3D electrodes are prepared by conformal MXene deposition on 3D‐printed polymer microlattices. The Ti₃C₂T_XMXene coating facilitates direct electron transfer, leading to the efficient detection of common antibiotics such as gentamicin and vancomycin. The 3D microporous architecture exposes greater electrochemically active MXene surface area, resulting in remarkable sensitivity for detecting gentamicin (10–1 mM) and vancomycin (100–1 mM), 1000 times more sensitive than control electrodes composed of 2D planar films of Ti₃C₂T_XMXene. To characterize the suitability of 3D microporous Ti₃C₂T_XMXene sensors for monitoring drug elution in bone tissue regeneration applications, osteoblast‐like (MG‐63) cells are seeded on the 3D MXene microlattices for 3, 5, and 7 days. Cell proliferation on the 3D microporous MXene is tracked over 7 days, demonstrating its promising biocompatibility and its clinical translation potential. Thus, 3D microporous Ti₃C₂T_XMXene can provide a platform for mediator‐free biosensing, enabling new applications for in vivo monitoring of drug elution.

Although tissue culture plastic has been widely employed for cell culture, the rigidity of plastic is not physiologic. Softer hydrogels used to culture cells have not been widely adopted in part because coupling chemistries are required to covalently capture extracellular matrix (ECM) proteins and support cell adhesion. To create an in vitro system with tunable stiffnesses that readily adsorbs ECM proteins for cell culture, a novel hydrophobic hydrogel system is presented via chemically converting hydroxyl residues on the dextran backbone to methacrylate groups, thereby transforming non‐protein adhesive, hydrophilic dextran to highly protein adsorbent substrates. Increasing methacrylate functionality increases the hydrophobicity in the resulting hydrogels and enhances ECM protein adsorption without additional chemical reactions. These hydrophobic hydrogels permit facile and tunable modulation of substrate stiffness independent of hydrophobicity or ECM coatings. Using this approach, it is shown that substrate stiffness and ECM adsorption work together to affect cell morphology and proliferation, but the strengths of these effects vary in different cell types. Furthermore, it is revealed that stiffness‐mediated differentiation of dermal fibroblasts into myofibroblasts is modulated by the substrate ECM. The material system demonstrates remarkable simplicity and flexibility to tune ECM coatings and substrate stiffness and study their effects on cell function.

Three-dimensional (3D) bio-printing is a rapidly growing field attempting to recreate functional tissues for medical and pharmaceutical purposes. The printability of multiple materials encapsulating various living cells can take this emerging effort closer to tissue regeneration. In our earlier research, we designed a Y-like nozzle connector system capable of switching materials between more than one filament with continuous deposition. The device had a fixed switching angle, was made from plastic, and was suitable for one-time use. This paper presents the extension of our previously proposed nozzle system. We considered 30°, 45°, 60°, and 90° angles (vertical and tilted) between the two materials and chose stainless steel as a material to fabricate those nozzle connectors. The overall material switching time was recorded and compared to analyze the effects of those various angles. Our previously developed hybrid hydrogel (4% Alginate and 4% Carboxymethyl Cellulose, CMC) was used as a test material to flow through the nozzle system. These in-house fabricated nozzle connectors are reusable, easy to clean, and sterile, allowing smooth material transition and flow.