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Electronic skin (E‐skin) that can mimic the flexibility and stretchability of human skin with sensing capabilities, holds transformative potential in robotics, wearable technology, and healthcare. However, developing E‐skin poses significant challenges such as creating durable materials with skin‐like flexibility, integrating biosensing abilities, and using advanced fabrication techniques for wearable or implantable applications. To overcome these hurdles, a 3D‐printed electronic skin utilizing a novel class of nanoengineered hydrogels with tunable electronic and thermal biosensing capabilities is fabricated. This methodology takes advantage of the shear–thinning behavior in hydrogel precursors, allowing to construct intricate 2D and 3D electronic structures. The elasticity of skin using triple crosslinking in a robust fungal exopolysaccharide, and pullulan is simulated, while defect‐rich 2D molybdenum disulfide (MoS2) nanoassemblies ensure high electrical conductivity. The addition of polydopamine nanoparticles enhances adhesion to wet tissue. The hydrogel exhibits outstanding flexibility, stretchability, adhesion, moldability, and electrical conductivity. A distinctive feature of this technology is the precise detection of dynamic changes in strain, pressure, and temperature. As a human motion tracker, phonatory‐recognition platform, flexible touchpad, and thermometer, this technology represents a breakthrough in flexible wearable skins and holds transformative potential for the future of robotics and human‐machine interfaces. [ABSTRACT FROM AUTHOR]

Internal hemorrhaging is a leading cause of death after traumatic injury on the battlefield. Although several surgical approaches such as the use of fibrin glue and tissue adhesive have been commercialized to achieve hemostasis, these approaches are difficult to employ on the battlefield and cannot be used for incompressible wounds. Here, we present shear-thinning nanocomposite hydrogels composed of synthetic silicate nanoplatelets and gelatin as injectable hemostatic agents. These materials are demonstrated to decrease in vitro blood clotting times by 77%, and to form stable clot-gel systems. In vivo tests indicated that the nanocomposites are biocompatible and capable of promoting hemostasis in an otherwise lethal liver laceration. The combination of injectability, rapid mechanical recovery, physiological stability, and the ability to promote coagulation result in a hemostat for treating incompressible wounds in out-of-hospital, emergency conditions.

The objective of this study was to develop an injectable and biocompatible hydrogel which can efficiently deliver a nanocomplex of graphene oxide (GO) and vascular endothelial growth factor-165 (VEGF) pro-angiogenic gene for myocardial therapy. For the study, an efficient nonviral gene delivery system using polyethylenimine (PEI) functionalized GO nanosheets (fGO) complexed with DNAVEGF was formulated and incorporated in the low-modulus methacrylated gelatin (GelMA) hydrogel to promote controlled and localized gene therapy. It was hypothesized that the fGOVEGF/GelMA nanocomposite hydrogels can efficiently transfect myocardial tissues and induce favorable therapeutic effects without invoking cytotoxic effects. To evaluate this hypothesis, a rat model with acute myocardial infarction was used, and the therapeutic hydrogels were injected intramyocardially in the peri-infarct regions. The secreted VEGF from in vitro transfected cardiomyocytes demonstrated profound mitotic activities on endothelial cells. A significant increase in myocardial capillary density at the injected peri-infarct region and reduction in scar area were noted in the infarcted hearts with fGOVEGF/GelMA treatment compared to infarcted hearts treated with untreated sham, GelMA and DNAVEGF/GelMA groups. Furthermore, the fGOVEGF/GelMA group showed significantly higher (p < 0.05, n = 7) cardiac performance in echocardiography compared to other groups, 14 days postinjection. In addition, no significant differences were noticed between GO/GelMA and non-GO groups in the serum cytokine levels and quantitative PCR based inflammatory microRNA (miRNA) marker expressions at the injected sites. Collectively, the current findings suggest the feasibility of a combined hydrogel-based gene therapy system for ischemic heart diseases using nonviral hybrid complex of fGO and DNA.

Development of three dimensional (3D) microenvironments that direct stem cell differentiation into functional cell types remains a major challenge in the field of regenerative medicine. Here, we describe a new platform to address this challenge by utilizing a robotic microarray spotter for testing stem cell fates inside various miniaturized cell-laden gels in a systematic manner. To demonstrate the feasibility of our platform, we evaluated the osteogenic differentiation of human mesenchymal stem cells (hMSCs) within combinatorial 3D niches. We were able to identify specific combinations, that enhanced the expression of osteogenic markers. Notably, these 'hit' combinations directed hMSCs to form mineralized tissue when conditions were translated to 3D macroscale hydrogels, indicating that the miniaturization of the experimental system did not alter stem cell fate. Overall, our findings confirmed that the 3D cell-laden gel microarray can be used for screening of different conditions in a rapid, cost-effective, and multiplexed manner for a broad range of tissue engineering applications.

A significant challenge in cardiac tissue engineering is the development of biomimetic grafts that can potentially promote myocardial repair and regeneration. A number of approaches have used engineered scaffolds to mimic the architecture of the native myocardium tissue and precisely regulate cardiac cell functions. However, previous attempts have not been able to simultaneously recapitulate chemical, mechanical, and structural properties of the myocardial extracellular matrix (ECM). In this study, we utilized an electrospinning approach to fabricate elastomeric biodegradable poly(glycerol sebacate) (PGS):gelatin nanofibrous scaffolds with a wide range of chemical composition, stiffness and anisotropy. Our findings demonstrated that through incorporation of PGS, it is possible to create nanofibrous scaffolds with well-defined anisotropy that mimic the left ventricular myocardium architecture. Furthermore, we studied attachment, proliferation, differentiation and alignment of neonatal rat cardiac fibroblast cells (CFs) as well as protein expression, alignment, and contractile function of cardiomyocyte (CMs) on PGS:gelatin scaffolds with variable amount of PGS. Notably, aligned nanofibrous scaffold, consisting of 33 wt. % PGS, induced optimal synchronous contractions of CMs while significantly enhanced cellular alignment. Overall, our study suggests that the aligned nanofibrous PGS:gelatin scaffold support cardiac cell organization, phenotype and contraction and could potentially be used to develop clinically relevant constructs for cardiac tissue engineering.

Granular hydrogels are a promising biomaterial for a wide range of biomedical applications, including tissue regeneration, drug/cell delivery, and 3D printing. These granular hydrogels are created by assembling microgels through the jamming process. However, current methods for interconnecting the microgels often limit their use due to the reliance on postprocessing for crosslinking through photoinitiated reactions or enzymatic catalysis. To address this limitation, we incorporated a thiol‐functionalized thermo‐responsive polymer into oxidized hyaluronic acid microgel assemblies. The rapid exchange rate of thiol‐aldehyde dynamic covalent bonds allows the microgel assembly to be shear‐thinning and self‐healing, with the phase transition behavior of the thermo‐responsive polymer serving as secondary crosslinking to stabilize the granular hydrogels network at body temperature. This two‐stage crosslinking system provides excellent injectability and shape stability, while maintaining mechanical integrity. In addition, the aldehyde groups of the microgels act as covalent binding sites for sustained drug release. These granular hydrogels can be used as scaffolds for cell delivery and encapsulation, and can be 3D printed without the need for post‐printing processing to maintain mechanical stability. Overall, our work introduces thermo‐responsive granular hydrogels with promising potential for various biomedical applications. [ABSTRACT FROM AUTHOR]

Hydrogels are widely used for therapeutic delivery applications due to their biocompatibility, biodegradability, and ability to control release kinetics by tuning swelling and mechanical properties. However, their clinical utility is hampered by unfavorable pharmacokinetic properties, including high initial burst release and difficulty in achieving prolonged release, especially for small molecules (<500 Da). The incorporation of nanomaterials within hydrogels has emerged as viable option as a method to trap therapeutics within the hydrogel and sustain release kinetics. Specifically, two-dimensional nanosilicate particles offer a plethora of beneficial characteristics, including dually charged surfaces, degradability, and enhanced mechanical properties within hydrogels. The nanosilicate–hydrogel composite system offers benefits not obtainable by just one component, highlighting the need for detail characterization of these nanocomposite hydrogels. This review focuses on Laponite, a disc-shaped nanosilicate with diameter of 30 nm and thickness of 1 nm. The benefits of using Laponite within hydrogels are explored, as well as examples of Laponite–hydrogel composites currently being investigated for their ability to prolong the release of small molecules and macromolecules such as proteins. Future work will further characterize the interplay between nanosilicates, hydrogel polymer, and encapsulated therapeutics, and how each of these components affect release kinetics and mechanical properties. [ABSTRACT FROM AUTHOR]

Glucose biosensors that could be subcutaneously injected and interrogated without a physically connected electrode and transmitter affixed to skin would represent a major advancement in reducing the user burden of continuous glucose monitors (CGMs). Towards this goal, an optical glucose biosensor was formed by strategically tailoring a thermoresponsive double network (DN) membrane to house a phosphorescence lifetime-based glucose sensing assay. This membrane was selected based on its potential to exhibit reduced biofouling via 'self-cleaning' due to cyclical deswelling/reswelling in vivo. The membrane was strategically tailored to incorporate oxygen-sensitive metalloporphyrin phosphor, Pd meso-tetra(sulfophenyl)-tetrabenzoporphyrin ([PdPh4(SO3Na)4TBP]3) (HULK) and glucose oxidase (GOx). Specifically, electrostatic interactions and colvalent bonds were used to stabilize HULK and GOx within the membrane, respectively. Enhancing the oxygen permeability of the membrane was necessary to achieve sensitivity of HULK/GOx to physiological glucose levels. Thus, silicone microparticles were incorporated at two concentrations. Key properties of SiHy-0.25 and SiHy-0.5 microparticle-containing compositions were compared to a control having no microparticles (SiHy-0). The discrete nature of the silicone microparticles maintained the desired thermosensitivity profile and did not impact water content. While the modulus decreased with silicone microparticle content, membranes were more mechanically robust versus a conventional hydrogel. SiHy-0.25, owing to apparent phase separation, displayed greater glucose diffusion and oxygen permeability versus SiHy-0.5. Furthermore, SiHy-0.25 biosensors exhibited the greatest glucose sensitivity range of 100 to 300 mg dL−1versus only 100 to 150 mg dL−1 for both SiHy-0 and SiHy-0.5 biosensors. [ABSTRACT FROM AUTHOR]

Dynamic hydrogels are promising biomaterials for various biomedical and biotechnological applications due to their ability to change physicochemical properties and functions reversibly and/or sequentially in a time‐ or stimuli‐dependent manner. In this study, a new class of dynamic hydrogels that are crosslinked by the in situ redox reactions of gold ions and disulfide groups are developed. Specifically, the gold ions initiate hydrogel formation via gold‐thiol crosslinking, transforming the hydrogel from an injectable hydrogel to a mechanically stable and tough hydrogel. Moreover, the in situ nucleation and growth of gold nanoparticles within the crosslinked hydrogel networks further enhance electrical conductivity. The current work demonstrates the utility of these dynamic hydrogels for 3D printing and drug delivery. [ABSTRACT FROM AUTHOR]

Herein, a method that uses direct‐ink‐write printing to fabricate engineering living materials (ELMs) that respond by undergoing a programmed shape change in response to specific molecules is reported. Stimuli‐responsiveness is imparted to ELMs by integrating genetically engineered yeast that only proliferate in the presence of specific biomolecules. This proliferation, in turn, leads to a shape change in the ELM in response to that biomolecule. These ELMs are fabricated by coprinting bioinks that contain multiple yeast strains. Locally, cellular proliferation leads to controllable shape change of the material resulting in up to a 370% increase in volume. Globally, the printed 3D structures contain regions of material that increase in volume and regions that do not under a given set of conditions, leading to programmable changes in form in response to target amino acids and nucleotides. Finally, this printing method is applied to design a reservoir‐based drug delivery system for the on‐demand delivery of a model drug in response to a specific biomolecule. [ABSTRACT FROM AUTHOR]

Belousov–Zhabotinsky (BZ) reactions have been used to investigate periodic spatial patterns due to the oscillatory nature of the reaction. However, these systems have not been confined, nor controlled, in macro‐scaled architectures, making it hard to translate observations to natural behavior. Here, a poly(electrolyte) complex is designed that can be ionically or covalently reinforced to construct 3D geometries with additive manufacturing techniques. Printed geometries varied in shape, size, and angle to investigate spatiotemporal pattern formation in 3D. Size variations correlated to trends in oscillating pattern frequencies, demonstrating a geometry effect on spatial alterations. Overall, the combination of 3D printing techniques with self‐oscillating chemical reactions allows to model, study, and further understand macro‐scale patterns observed in nature. The proposed approach can be used to design smart structure to replicate biological oscillators such as cardiac arrhythmias, neuron signaling, and camouflage skin patterns. [ABSTRACT FROM AUTHOR]