Living Microneedle Patch with Adipose-Derived Stem Cells Embedding for Diabetic Ulcer Healing

Stem cells have demonstrated values in diabetic ulcer (DU) treatments. Challenges in this area are focused on enhancing the localized curative effects of stem cells and improving diabetic wound healing efficiently. Herein, a novel living microneedle (MN) patch is presented as a localized delivery system of bioactive platelet derived growth factor D (PDGF-D) and human adipose-derived stem cells (ADSCs) for DU wound treatment. Compared with traditional complicated stem cell carriers, the MN patch can keep stem cell viability for ADSCs encapsulation and delivery, and possesses good mechanical strengths to penetrate the local skin wounds noninvasively. It is demonstrated that the delivery ADSCs are with the abilities of angiogenesis promotion during the DU wound healing; while the additive PDGF-D can contribute significantly to the proliferation of ADSCs, strengthening the cell function of ADSCs and further facilitating the healing processes. Thus, living MN patches accelerate vascularization, tissue regeneration, and collagen deposition in a wounded diabetic mouse model, suggesting their potential application to DU wound healing and other therapeutic applications.     

A Self-Thickening and Self-Strengthening Strategy for 3D Printing High-Strength and Antiswelling Supramolecular Polymer Hydrogels as Meniscus Substitutes

3D printing of high-strength and antiswelling hydrogel-based load-bearing soft tissue scaffolds with similar geometric shape to natural tissues remains a great challenge owing to insurmountable trade-off between strength and printability. Herein, capitalizing on the concentration-dependent H-bonding-strengthened mechanism of supramolecular poly(N-acryloyl glycinamide) (PNAGA) hydrogel, a self-thickening and self-strengthening strategy, that is, loading the concentrated NAGA monomer into the thermoreversible low-strength PNAGA hydrogel is proposed to directly 3D printing latently H-bonding-reinforced hydrogels. The low-strength PNAGA serves to thicken the concentrated NAGA monomer, affording an appropriate viscosity for thermal-assisted extrusion 3D printing of soft PNAGA hydrogels bearing NAGA monomer and initiator, which are further polymerized to eventually generate high-strength and antiswelling hydrogels, due to the reconstruction of strong H-bonding interactions from postcompensatory PNAGA. Diverse polymer hydrogels can be printed with self-thickened corresponding monomer inks. Further, the self-thickened high-strength PNAGA hydrogel is printed into a meniscus, which is implanted in rabbit's knee as a substitute with in vivo outcome showing an appealing ability to efficiently alleviate the cartilage surface wear. The self-thickening strategy is applicable to directly printing a variety of polymer-hydrogel-based tissue engineering scaffolds without sacrificing mechanical strength, thus circumventing problems of printing high-strength hydrogels and facilitating their application scope.     

A Review of Design and Fabrication Methods for Nanoparticle Network Hydrogels for Biomedical,Environmental, and Industrial Applications

Nanoparticle network hydrogels (NNHs) in which nanoparticles are used as a key building block to build the gel network have attracted significant interest given their potential to leverage the favorable properties of both hydrogels (e.g., hydrophilicity, tunable pore sizes, mechanics, etc.) and a variety of different nanoparticles (e.g., high surface area, chemical activity, independently tunable porosity, mechanics) to create new functional materials. Herein, recent progress in the design and use of NNHs is comprehensively reviewed, with an emphasis on defining the typical gel morphologies/architectures that can be achieved with NNHs, the typical crosslinking approaches used to fabricate NNHs, the fundamental properties and functional benefits of NNHs, and the reported applications of NNHs in electronics (flexible electronics, sensors), environmental (sorbents, separations), agriculture, self-cleaning-materials, and biomedical (drug delivery, tissue engineering) applications. In particular, the way in which the NNH structure is applied to improve the performance of the hydrogel in each application is emphasized, with the aim to develop a set of principles that can be used to rationally design NNHs for future uses.     

Light-Fueled Nonequilibrium and Adaptable Hydrogels for Highly Tunable Autonomous Self-Oscillating Functions

Nonequilibrium oscillation fueled by dissipating chemical energy is ubiquitous in living systems for realizing a broad range of complex functions. The design of synthetic materials that can mimic their biological counterparts in the production of dissipative structures and autonomous oscillations is of great interest but remains challenging. Here, a series of environmentally adaptable hydrogels functionalized with photoswitchable spiropyran derivatives that display a tunable equilibrium-shifting capability, thus endowing those hydrogels with a high degree of freedom and flexibility is reported. Such nonequilibrium hydrogels are able to responsively adapt their shapes under constant light illumination due to asymmetric deswelling, which in turn generates self-shadowing and consequently creates autonomous self-oscillating behaviors through a negative feedback process. Diverse oscillation modes including bending, twisting, and snap-through buckling with tunable frequency and amplitude are widely observed in three different molecular systems. Density functional theory calculations and finite element simulations further demonstrated the robustness of such a photoadaptable self-oscillation mechanism. This study provides a useful molecular design strategy for construction of highly adaptable hydrogels with potential applications in self-sustained soft robots and autonomous devices.     

Ultra-Histocompatible and Electrophysiological-Adapted PEDOT-Based Hydrogels Designed for Cardiac Repair

Currently, although conducting polymers have exhibited potential electrophysiological modulation, designing bioinspired ultra-histocompatible conducting polymers remains a long-standing challenge. Moreover, the water dispersibility, conductivity, and biocompatibility of conducting polymers are incompatible, which restricts their application in tissue engineering. Herein, a multilevel template dispersion strategy is presented to produce poly(3,4-ethylenedioxythiophene):(dextran sulfate/carboxymethyl chitosan) (PEDOT:(DSS/CMCS)) with biocompatibility superior to that of commercial poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) without sacrificing processability and conductivity. The PEDOT:(DSS/CMCS) and oxidized dextran solutions form an injectable PEDOT-based hydrogel (PDCOH) mediated by dynamic covalent imine bonds under mild conditions. The PDCOH has a tissue-matched modulus and conductivity to adapt to the mechanical environment of dynamic tissue and modulate fibrosis-induced electrical decoupling. The PDCOH combined with adipose-derived stem cells demonstrates superior cardiac repair effects over cell suspensions and nonconductive hydrogels, inhibiting ventricular remodeling, reducing fibrous scarring, promoting vascular regeneration, and restoring electrophysiological and pulsatile functions.     

Hydration-Induced Void-Containing Hydrogels for Encapsulation and Sustained Release of Small Hydrophilic Molecules

Efficient encapsulation and sustained release of small hydrophilic molecules from traditional hydrogel systems are challenging due to the large mesh size of 3D networks and high water content. Furthermore, the encapsulated molecules are prone to early release from the hydrogel prior to use, resulting in a short shelf life of the formulation. Here, a hydration-induced void-containing hydrogel (HVH) based on hyperbranched polyglycerol-poly(propylene oxide)-hyperbranched polyglycerol (HPG-PPG-HPG) as a robust and efficient delivery system is presented for small hydrophilic molecules. Specifically, after the HPG-PPG-HPG is incubated overnight at 4 °C in the drug solution, it is hydrated into a hydrogel containing micron-sized voids, which can encapsulate hydrophilic drugs and achieve 100% drug encapsulation efficiency. In addition, the voids are surrounded by a densely packed polymer matrix, which restricts drug transport to achieve sustained drug release. The hydrogel/drug formulation can be stored for several months without changing the drug encapsulation and release properties. HVH hydrogels are injectable due to shear thinning properties. In rats, a single injection of the HPG-PPG-HPG hydrogel containing 8 µg of tetrodotoxin (TTX) produces sciatic nerve block lasting up to 10 h without any TTX-related systemic toxicity nor local toxicity to nerves and muscles.     

Phase Change Hydrogels for Bio-Inspired Adhesion and Energy Exchange Applications

The adhesion strategies of the gecko's toe through surface adaptation of spatulas to increase contact area and the snail's epiphragm via dehydration-induced solidification to lock interfaces are combined to design a class of adhesion-switchable hydrogels. The hydrogels are made via incorporating CH₃COONa·3H₂O salt (SA) into polyacrylamide (PAM) aqueous networks to construct supersaturated and stimuli-responsive phase change materials (PAM-SA). The crystallization dramatically strengthens the mechanical properties, and tensile Young's moduli are 340.7 and 0.1 MPa for crystalline C-PAM-SA-120% and soft PAM hydrogel. As a result, PAM-SA-120% shows excellent adhesive performance (adhesion strength, 348 kPa) compared with PAM hydrogel adhesive (adhesion strength, 7 kPa). The stimuli-induced crystallization from H-PAM-SA-120% phase change hydrogels releases thermal controllably, which can be utilized for thermochromic materials and thermotherapy.     

Graphene Oxide‐Templated Conductive and Redox‐Active Nanosheets Incorporated Hydrogels for Adhesive Bioelectronics

2D conductive nanosheets are central to electronic applications because of their large surface areas and excellent electronic properties. However, tuning the multifunctions and hydrophilicity of conductive nanosheets are still challenging. Herein, a green strategy is developed for fabricating conductive, redox‐active, water‐soluble nanosheets via the self‐assembly of poly(3,4‐ethylenedioxythiophene) (PEDOT) on the polydopamine‐reduced and sulfonated graphene oxide (PSGO) template. The conductivity and hydrophilicity of nanosheets are highly improved by PSGO. The nanosheets are redox active due to the abundant catechol groups and can be used as versatile nanofillers in developing conductive and adhesive hydrogels. The nanosheets create a mussel‐inspired redox environment inside the hydrogel networks and endow the hydrogel with long‐term and repeatable adhesiveness. This hydrogel is biocompatible and can be implanted for biosignals detection in vivo. This mussel‐inspired strategy for assembling 2D nanosheets can be adapted for producing diverse multifunctional nanomaterials, with various potential applications in bioelectronics.     

Highly Oxidation-Resistant and Self-Healable MXene-Based Hydrogels for Wearable Strain Sensor

Very recently, MXene-based wearable hydrogels have emerged as promising candidates for epidermal sensors due to their tissue-like softness and unique electrical and mechanical properties. However, it remains a challenge to achieve MXene-based hydrogels with reliable sensing performance and prolonged service life, because MXene inevitably oxidizes in water-containing system of the hydrogels. Herein, catechol-functionalized poly(vinyl alcohol) (PVA-CA)-based hydrogels is proposed to inhibit the oxidation of MXene, leading to rapid self-healing and superior strain sensing behaviors. Sufficient interaction of hydrophobic catechol groups with the MXene surface reduces the oxidation-accessible sites in the MXene for reaction with water and eventually suppresses the oxidation of MXene in the hydrogel. Furthermore, the PVA-CA-MXene hydrogel is demonstrated for use as a strain sensor for real-time motion monitoring, such as detecting subtle human motions and handwriting. The signals of PVA-CA-MXene hydrogel sensor can be accurately classified using deep learning models.     

Self-Repairing and Damage-Tolerant Hydrogels for Efficient Solar-Powered Water Purification and Desalination

Solar-driven interfacial evaporation has emerged as an innovative and sustainable technology for efficient, clean water production. Real-world applications depend on new classes of low-cost, lightweight, and robust materials that can be integrated into one monolithic device, which withstands a variety of realistic conditions on open water. Self-repairing building blocks are highly desired to prevent permanent failures, recover original functions and maintain the lifetime of interfacial steam generators, although related studies are scarce to date. For the first time, a monolithic, durable, and self-floating interfacial steam generator with well-defined structures is demonstrated by integrating self-healing hydrogels through facile processes in surface modulation and device fabrication. High and stable water evaporation rates over 2.0 kg m⁻² h⁻¹ are attained under 1 sun on both fresh water and brine with a broad range of salinity (36–210 g kg⁻¹). The solar evaporation and desalination performance are among the best-performing interfacial steam generators and surpass a majority of devices that are constructed by composite polymers as structural components. This study provides a perspective and highlights the future opportunities in self-healing and damage-tolerant materials that can simultaneously improve the performance, durability, and lifetime of interfacial steam generators in real-world applications.     

Photogenerated Aldehydes for Protein Patterns on Hydrogels and Guidance of Cell Behavior

The immobilization of proteins to hydrogels is important and plays a significant role to provide suitable biomimetic material as extracellular matrix for cell behavior mediation. This study describes a novel and universal strategy for photopatterning unmodified proteins on hydrogels. The methodology creates photogenerated aldehyde regions within a protein‐resistant hydrogel and then conjugates unmodified proteins by mild imine ligation with spatial, temporal, and dosage control. The relatively stable aldehyde intermediate enables the facile and highly efficient covalent immobilization of proteins by a postfunctionalization methodology and the sequential protein patterns provide an easy access to control the identity and dynamic change of proteins presented to cells on demand, thus mediating cell behaviors. This approach provides important opportunities for understanding and controlling cell behavior mediated by proteins, and opens up new avenues for hydrogels in tissue engineering and biotechnology applications.     

Patterned Hydrogels for Controlled Platelet Adhesion from Whole Blood and Plasma

This work describes the preparation and properties of hydrogel surface chemistries enabling controlled and well‐defined cell adhesion. The hydrogels may be prepared directly on plastic substrates, such as polystyrene slides or dishes, using a quick and experimentally simple photopolymerization process, compatible with photolithographic and microfluidic patterning methods. The intended application for these materials is as substrates for diagnostic cell adhesion assays, particularly for the analysis of human platelet function. The non‐specific adsorption of fibrinogen, a platelet adhesion promoting protein, is shown to be completely inhibited by the hydrogel, provided that the film thickness is sufficient (>5 nm). This allows the hydrogel to be used as a matrix for presenting selected bioactive ligands without risking interference from non‐specifically adsorbed platelet adhesion factors, even in undiluted whole blood and blood plasma. This concept is demonstrated by preparing patterns of proteins on hydrogel surfaces, resulting in highly controlled platelet adhesion. Further insights into the protein immobilization and platelet adhesion processes are provided by studies using imaging surface plasmon resonance. The hydrogel surfaces used in this work appear to provide an ideal platform for cell adhesion studies of platelets, and potentially also for other cell types.     

Magnetic Living Hydrogels for Intestinal Localization,Retention, and Diagnosis

Natural microbial sensing circuits can be rewired into new gene networks to build living sensors that detect and respond to disease-associated biomolecules. However, synthetic living sensors, once ingested, are cleared from the gastrointestinal (GI) tract within 48 h; retaining devices in the intestinal lumen is prone to intestinal blockage or device migration. To localize synthetic microbes and safely extend their residence in the GI tract for health monitoring and sustained drug release, an ingestible magnetic hydrogel carrier is developed to transport diagnostic microbes to specific intestinal sites. The magnetic living hydrogel is localized and retained by attaching a magnet to the abdominal skin, resisting the peristaltic waves in the intestine. The device retention is validated in a human intestinal phantom and an in vivo rodent model, showing that the ingestible hydrogel maintains the integrated living bacteria for up to seven days, which allows the detection of heme for GI bleeding in the harsh environment of the gut. The retention of microelectronics is also demonstrated by incorporating a temperature sensor into the magnetic hydrogel carrier.     

Injectability of Biosynthetic Hydrogels: Consideration for Minimally Invasive Surgical Procedures and 3D Bioprinting

Injectable hydrogels are often preferred when designing carriers for cell therapy or developing new bio-ink formulations. Biosynthetic hydrogels, which are a class of materials made with a hybrid design strategy, can be advantageous for endowing injectability while maintaining biological activity of the material. The chemical modification required to make these gels injectable by specific crosslinking pathways can be challenging and also make the hydrogels inhospitable to cells. Therefore, most efforts to functionalize biosynthetic hydrogel precursors toward injectability in the presence of cells try to balance between chemical and biological functionality, in order to preserve cell compatibility while addressing the injectability design challenges. Accordingly, hydrogel crosslinking strategies have evolved to include the use of photoinitiated “click” chemistry or bio-orthogonal reactions with rapid gelation kinetics and minimal cyto-toxicity required when working with cell-compatible hydrogel systems. With many new injectable biosynthetic materials emerging, their impact in cell-based regenerative medicine and bioprinting is also becoming more apparent. This review covers the main strategies that are used to endow biosynthetic polymers with injectability through rapid, cyto-compatible physical or covalent crosslinking and the main considerations for using the resulting injectable hydrogels in cell therapy, tissue regeneration, and bioprinting.     

Macroporous Hydrogels for Fast and Reversible Switching between Transparent and Structurally Colored States

Colloidal crystals have been used for creating stimuli‐responsive photonic materials. Here, macroporous hydrogels are designed, through a simple and reproducible protocol, that rapidly and reversibly switch between highly transparent and structurally colored states. The macroporous hydrogels are prepared by film‐casting photocurable dispersions of silica particles in hydrogel‐forming resins and selectively removing silica particles. The silica particles spontaneously form a nonclose‐packed array due to repulsive interparticle interaction, which form the regular array of cavities after removal. However, the cavities are randomly collapsed by drying, losing a long‐range order and rendering the materials highly transparent. When the hydrogels are swollen by either water, ethanol, or the mixture, the regular array is restored, which develops brilliant structural colors. This switching is completed in tens of seconds and repeatable without any hysteresis. The resonant wavelength depends on the composition of the water–ethanol mixture, where the dramatic shift occurs in one‐component‐rich mixtures due to the composition of the hydrogel. Micropatterns can be designed to have distinct domains of the macroporous hydrogels, which are transparent at the dried state and disclose encrypted graphics and unique reflectance spectra at the wet state. This class of solvent‐responsive photonic hydrogels is potentially useful for alcohol sensors and user‐interactive anti‐counterfeiting materials.     

Highly Stretchable,Resilient, Adhesive,and Self-Healing Ionic Hydrogels for Thermoelectric Application

Harvesting low-grade waste heat from the natural environment with thermoelectric materials is considered as a promising solution for the sustainable energy supply for wearable electronic devices. For practical applications, it is desirable to endow the thermoelectric materials with excellent mechanical and self-healing properties, which remains a great challenge. Herein, the design and characterization of a series of high-performance ionic hydrogels for soft thermoelectric generator applications are reported. Composed of a physically cross-linked network of polyacrylic acid (PAA) and polyethylene glycol (PEO) doped with sodium chloride, the resulting PAA-PEO-NaCl ionic hydrogels demonstrates impressive mechanical strength (breaking stress >1.3 MPa), stretchability (>1100%), and toughness (up to 7.34 MJ m⁻³). Moreover, the reversible hydrogen bonding interaction and chain entanglement render the ionic hydrogels with excellent mechanical resilience, adhesion properties, and self-healing properties. At ambient conditions, the electrochemical and thermoelectric performance of the ionic hydrogels can be restored immediately from physical damage such as cutting, and the mechanical healing can be completely restored within 24 h. At the optimized composition, the Seebeck coefficient of the ionic hydrogels can reach 3.26 mV K⁻¹ with a low thermal conductivity of 0.321 W m⁻¹ K⁻¹. Considering the excellent mechanical properties and thermoelectric performance, it is believed that the ionic hydrogels are widely applicable in ionic thermoelectric capacitors to convert low-grade heat into electricity for soft electronic devices.     

Muscle-Inspired MXene Conductive Hydrogels with Anisotropy and Low-Temperature Tolerance for Wearable Flexible Sensors and Arrays

Conductive hydrogels as flexible electronic devices, not only have unique attractions but also meet the basic need of mechanical flexibility and intelligent sensing. How to endow anisotropy and a wide application temperature range for traditional homogeneous conductive hydrogels and flexible sensors is still a challenge. Herein, a directional freezing method is used to prepare anisotropic MXene conductive hydrogels that are inspired by ordered structures of muscles. Due to the anisotropy of MXene conductive hydrogels, the mechanical properties and electrical conductivity are enhanced in specific directions. The hydrogels have a wide temperature resistance range of −36 to 25 °C through solvent substitution. Thus, the muscle-inspired MXene conductive hydrogels with anisotropy and low-temperature resistance can be used as wearable flexible sensors. The sensing signals are further displayed on the mobile phone as images through wireless technology, and images will change with the collected signals to achieve motion detection. Multiple flexible sensors are also assembled into a 3D sensor array for detecting the magnitude and spatial distribution of forces or strains. The MXene conductive hydrogels with ordered orientation and anisotropy are promising for flexible sensors, which have broad application prospects in human–machine interface compatibility and medical monitoring.     

Surface Patterning of Hydrogels for Programmable and Complex Shape Deformations by Ion Inkjet Printing

Convenient patterning and precisely programmable shape deformations are crucial for the practical applications of shape deformable hydrogels. Here, a facile and versatile computer‐assisted ion inkjet printing technique is described that enables the direct printing of batched, very complicated patterns, especially those with well‐defined, programmable variation in cross‐linking densities, on one or both surfaces of a large‐sized hydrogel sample. A mechanically strong hydrogel containing poly(sodium acrylate) is first prepared, and then digital patterns are printed onto the hydrogel surfaces by using a commercial inkjet printer and an aqueous ferric solution. The complexation between the polyelectrolyte and ferric ions increases the cross‐linking density of the printed regions, and hence the gel sample can undergo shape deformation upon swelling/deswelling. The deformation rates and degrees of the hydrogels can be conveniently adjusted by changing the printing times or the different/gradient grayscale distribution of designed patterns. By printing appropriate patterns on one or both surfaces of the hydrogel sheets, many complex 3D shapes are obtained from shape deformations upon swelling/deswelling, such as cylindrical shell and forsythia flower (patterns on one surface), ding (patterns on both surfaces), blooming flower (different/gradient grayscale distributive patterns on one surface), and non‐Euclidean plates (different/gradient grayscale distributive patterns on both surfaces).