Design and Applications of Photoresponsive Hydrogels

Hydrogels are the most relevant biochemical scaffold due to their tunable properties, inherent biocompatibility, and similarity with tissue and cell environments. Over the past decade, hydrogels have developed from static materials to “smart” responsive materials adapting to various stimuli, such as pH, temperature, chemical, electrical, or light. Light stimulation is particularly interesting for many applications because of the capability of contact‐free remote manipulation of biomaterial properties and inherent spatial and temporal control. Moreover, light can be finely adjusted in its intrinsic properties, such as wavelength and intensity (i.e., the energy of an individual photon as well as the number of photons over time). Water is almost transparent for light in the photochemically relevant range (NIR–UV), thus hydrogels are well‐suited scaffolds for light‐responsive functionality. Hydrogels' chemical and physical variety combined with light responsiveness makes photoresponsive hydrogels ideal candidates for applications in several fields, ranging from biomaterials, medicine to soft robotics. Herein, the progress and new developments in the field of light‐responsive hydrogels are elaborated by first introducing the relevant photochemistries before discussing selected applications in detail.     

25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine

Hydrogels are hydrophilic polymer‐based materials with high water content and physical characteristics that resemble the native extracellular matrix. Because of their remarkable properties, hydrogel systems are used for a wide range of biomedical applications, such as three‐dimensional (3D) matrices for tissue engineering, drug‐delivery vehicles, composite biomaterials, and as injectable fillers in minimally invasive surgeries. In addition, the rational design of hydrogels with controlled physical and biological properties can be used to modulate cellular functionality and tissue morphogenesis. Here, the development of advanced hydrogels with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light‐sensitive, composite, and shape‐memory hydrogels. Emerging technologies developed over the past decade to control hydrogel architecture are also discussed and a number of potential applications and challenges in the utilization of hydrogels in regenerative medicine are reviewed. It is anticipated that the continued development of sophisticated hydrogels will result in clinical applications that will improve patient care and quality of life.     

DNA Hydrogels and Microgels for Biosensing and Biomedical Applications

DNA hydrogels, which take advantage of the unique properties of functional DNA motifs, such as specific molecular recognition, programmable and high-precision assembly, multifunctionality, and excellent biocompatibility, have attracted increasing research interest in the past two decades in diverse fields, especially in biosensing and biomedical applications. The responsiveness of smart DNA hydrogels to external stimuli by changing their swelling volume, crosslinking density, and optical or mechanical properties has facilitated the development of DNA-hydrogel-based in vitro biosensing systems and actuators. Furthermore, reducing the sizes of DNA hydrogels to the micro- and nanoscale leads to better responsiveness and delivery capacity, thereby making them excellent candidates for rapid detection, in vivo real-time sensing, and drug release applications. Here, the recent progress in the development of smart DNA hydrogels and DNA microgels for biosensing and biomedical applications is summarized, and the current challenges as well as future prospects are also discussed.     

Sensitivity Tuning through Additive Heterogeneous Plasmon Coupling between 3D Assembled Plasmonic Nanoparticle and Nanocup Arrays

Plasmonic substrates have fixed sensitivity once the geometry of the structure is defined. In order to improve the sensitivity, significant research effort has been focused on designing new plasmonic structures, which involves high fabrication costs; however, a method is reported for improving sensitivity not by redesigning the structure but by simply assembling plasmonic nanoparticles (NPs) near the evanescent field of the underlying 3D plasmonic nanostructure. Here, a nanoscale Lycurgus cup array (nanoLCA) is employed as a base colorimetric plasmonic substrate and an assembly template. Compared to the nanoLCA, the NP assembled nanoLCA (NP‐nanoLCA) exhibits much higher sensitivity for both bulk refractive index sensing and biotin–streptavidin binding detection. The limit of detection of the NP‐nanoLCA is at least ten times smaller when detecting biotin–streptavidin conjugation. The numerical calculations confirm the importance of the additive plasmon coupling between the NPs and the nanoLCA for a denser and stronger electric field in the same 3D volumetric space. Tunable sensitivity is accomplished by controlling the number of NPs in each nanocup, or the number density of the hot spots. This simple yet scalable and cost‐effective method of using additive heterogeneous plasmon coupling effects will benefit various chemical, medical, and environmental plasmon‐based sensors.     

Highly Efficient and Environmentally Friendly Fabrication of Robust,Programmable, and Biocompatible Anisotropic,All‐Cellulose,Wrinkle‐Patterned Hydrogels for Cell Alignment

Wrinkled hydrogels from biomass sources are potential structural biomaterials. However, for biorelated applications, engineering scalable, structure‐customized, robust, and biocompatible wrinkled hydrogels with highly oriented nanostructures and controllable intervals is still a challenge. A scalable biomass material, namely cellulose, is reported for customizing anisotropic, all‐cellulose, wrinkle‐patterned hydrogels (AWHs) through an ultrafast, auxiliary force, acid‐induced gradient dual‐crosslinking strategy. Direct immersion of a prestretched cellulose alkaline gel in acid and relaxation within seconds allow quick buildup of a consecutive through‐thickness modulus gradient with acid‐penetration‐directed dual‐crosslinking, confirmed by visual 3D Raman microscopy imaging, which drives the formation of self‐wrinkling structures. Moreover, guided by quantitative mechanics simulations, the structure of AWHs is found to exhibit programmable intervals and aligned nanostructures that differ between ridge and valley regions and can be controlled by tuning the prestretching strain and acid treatment time, and these AWHs successfully induce cell alignment. Thus, a new avenue is opened to fabricate polysaccharide‐derived, programmable, anisotropic, wrinkled hydrogels for use as biomedical materials via a bottom‐up method.     

Hydrophobic Hydrogels with Fruit‐Like Structure and Functions

Normally, a polymer network swells in a good solvent to form a gel but the gel shrinks in a poor solvent. Here, an abnormal phenomenon is reported: some hydrophobic gels significantly swell in water, reaching water content as high as 99.6 wt%. Such abnormal swelling behaviors in the nonsolvent water are observed universally for various hydrophobic organogels containing omniphilic organic solvents that have a higher affinity to water than to the hydrophobic polymers. The formation of a semipermeable skin layer due to rapid phase separation, and the asymmetric diffusion of water molecules into the gel driven by the high osmotic pressure of the organic solvent–water mixing, are found to be the reasons. As a result, the hydrophobic hydrogels have a fruit‐like structure, consisting of hydrophobic skin and water‐trapped micropores, to display various unique properties, such as significantly enhanced strength, surface hydrophobicity, and antidrying, despite their extremely high water content. Furthermore, the hydrophobic hydrogels exhibit selective water absorption from concentrated saline solutions and rapid water release at a small pressure like squeezing juices from fruits. These novel functions of hydrophobic hydrogels will find promising applications, e.g., as materials that can automatically take the fresh water from seawater.     

Performing Logical Operations with Stimuli‐Responsive Building Blocks

Chemical logic gates can be fabricated by synthesizing molecules that have the ability to detect external stimuli (e.g., temperature or pH) and provide logical outputs. It is, however, challenging to fabricate a system that consists of many logic gates using this method: complex molecules can be difficult to synthesize and these logic gates typically cannot be integrated together. Here, we fabricated different types of logic gates by assembling a combination of different types of stimuli‐responsive hydrogels that change their size under the influence of one type of stimulus. Importantly, the preparation of these stimuli‐responsive hydrogels is widely reported and technically simple. Through designing the geometry of the systems, we fabricated the YES, NOT, OR, AND, NOR, and NAND gates. Although the hydrogels respond to different types of stimuli, their outputs are the same: a change in size of the hydrogel. Hence, we show that the logic gates can be integrated easily (e.g., by connecting an AND gate to an OR gate). In addition, we fabricated a standalone system with the size of a normal drug tablet (i.e., a “smart tablet”) that can analyze (or diagnose) different stimuli and control the release of a chemical (or drug) via the logic gates.     

Dynamic Hyaluronan Hydrogels with Temporally Modulated High Injectability and Stability Using a Biocompatible Catalyst

Injectable and biocompatible hydrogels have become increasingly important for cell transplantation to provide mechanical protection of cells during injection and a stable scaffold for cell adhesion post‐injection. Injectable hydrogels need to be easily pushed through a syringe needle and quickly recover to a gel state, thus generally requiring noncovalent or dynamic cross‐linking. However, a dilemma exists in the design of dynamic hydrogels: hydrogels with fast exchange of cross‐links are easier to eject using less force, but lack long‐term stability; in contrast, slow exchange of cross‐links improves stability, but compromises injectability and thus the ability to protect cells under flow. A new concept to resolve this dilemma using a biocompatible catalyst to modulate the dynamic properties of hydrogels at different time points of application to have both high injectability and high stability is presented. Hyaluronic acid based hydrogels are formed through dynamic covalent hydrazone cross‐linking in the presence of a biocompatible benzimidazole‐based catalyst. The catalyst accelerates the formation and exchange of hydrazone bonds, enhancing injectability, but rapidly diffuses away from the hydrogel after injection to retard the exchange and improve the long‐term stability for cell culture.     

Ag/PVP/PVA抗菌水凝胶的制备及性能

采用液相还原法,以聚乙烯吡咯烷酮(PVP)为保护剂,水合肼直接还原硝酸银溶液得到稳定分散的纳米银溶胶,并通过冷冻(-20℃)、解冻(20℃)法合成了物理交联的Ag/PVP/PVA水凝胶。利用透射电子显微镜(TEM)、紫外可见光谱(UV-vis)、X射线衍射(XRD)以及红外分析(FT-IR)对制备的复合材料进行了表征,以大肠杆菌为细菌模型测试了样品的抗菌性能并分析了抗菌原理。结果表明,所得银溶胶中纳米银平均粒径约为50 nm,由于纳米银的引入,该新型水凝胶具有抗菌性能,是一种具有开发前景的复合材料。     

Highly Elastic and Ultratough Hybrid Ionic–Covalent Hydrogels with Tunable Structures and Mechanics

Hybrid ionically–covalently crosslinked double‐network (DN) hydrogels are attracting increasing attention on account of their self‐recovery ability and fatigue resistance, but their relative low mechanical strength and tedious performance adjustment severely limit their applications. Herein, a new strategy to concurrently fabricate hybrid ionic–covalent DN hydrogels and modulate their structures and mechanics is reported, in which an in situ formed chitosan ionic network is incorporated by post‐crosslinking the chitosan‐based composite hydrogel using multivalent anions solutions. The obtained hybrid DN hydrogels exhibit predominant mechanical properties including superior elastic modulus, high tensile strength, and ultrahigh fracture energy because of the more efficient energy dissipation of rigid short‐chain chitosan network. Notably, the swollen hydrogels still remain mechanically strong and tough even after immersion in water for 24 h. More significantly, simply changing the post‐crosslinking time can vary the compactness and rigidity of the chitosan network in situ, achieving flexible and efficient modulation of the structures and mechanics of the hybrid DN hydrogels. This study opens up a new horizon in the preparation and regulation of DN hydrogels for promising applications in tissue scaffolds, actuators, and wearable devices.     

Tough Hydrogels with Fast,Strong, and Reversible Underwater Adhesion Based on a Multiscale Design

Hydrogels have promising applications in diverse areas, especially wet environments including tissue engineering, wound dressing, biomedical devices, and underwater soft robotics. Despite strong demands in such applications and great progress in irreversible bonding of robust hydrogels to diverse synthetic and biological surfaces, tough hydrogels with fast, strong, and reversible underwater adhesion are still not available. Herein, a strategy to develop hydrogels demonstrating such characteristics by combining macroscale surface engineering and nanoscale dynamic bonds is proposed. Based on this strategy, excellent underwater adhesion performance of tough hydrogels with dynamic ionic and hydrogen bonds, on diverse substrates, including hard glasses, soft hydrogels, and biological tissues is obtained. The proposed strategy can be generalized to develop other soft materials with underwater adhesion.     

Ascidian-Inspired Temperature-Switchable Hydrogels with Antioxidant Fullerenols for Protecting Radiation-Induced Oral Mucositis and Maintaining the Homeostasis of Oral Microbiota

A key characteristic of radiation-induced oral mucositis (RIOM) is oxidative stress mediated by the “reactive oxygen species (ROS) storm” generated from water radiolysis, resulting in severe pathological lesions, accompanied by a disturbance of oral microbiota. Therefore, a sprayable in situ hydrogel loaded with “free radical sponge” fullerenols (FOH) is developed as antioxidant agent for RIOM radioprotection. Inspired by marine organisms, 3,4,5-trihydroxyphenylalanine (TOPA) which is enriched in ascidians is grafted to clinically approved temperature-switchable Pluronic F127 to produce gallic acid (containing the TOPA fragment)-modified Pluronic F127 (MGA) hydrogels to resist the fast loss of FOH via biomimetic adhesion during oral movement and saliva erosion. Based on this, progressive RIOM found in mice is alleviated by treatment of FOH-loaded MGA hydrogels whether pre-irradiation prophylactic administration or post-irradiation therapeutic administration, which contributes to maintaining the homeostasis of oral microbiota. Mechanistically, FOH inhibits cell apoptosis by scavenging radiation-induced excess ROS and up-regulates the inherent enzymatic antioxidants, thereby protecting the proliferation and migration of mucosal epithelial cells. In conclusion, this work not only provides proof-of-principle evidence for the oral radioprotection of FOH by blocking the “ROS storm”, but also provides an effective and easy-to-use hydrogel system for mucosal in situ administration.     

Nanoreinforced Hydrogels for Tissue Engineering: Biomaterials that are Compatible with Load‐Bearing and Electroactive Tissues

Given their highly porous nature and excellent water retention, hydrogel‐based biomaterials can mimic critical properties of the native cellular environment. However, their potential to emulate the electromechanical milieu of native tissues or conform well with the curved topology of human organs needs to be further explored to address a broad range of physiological demands of the body. In this regard, the incorporation of nanomaterials within hydrogels has shown great promise, as a simple one‐step approach, to generate multifunctional scaffolds with previously unattainable biological, mechanical, and electrical properties. Here, recent advances in the fabrication and application of nanocomposite hydrogels in tissue engineering applications are described, with specific attention toward skeletal and electroactive tissues, such as cardiac, nerve, bone, cartilage, and skeletal muscle. Additionally, some potential uses of nanoreinforced hydrogels within the emerging disciplines of cyborganics, bionics, and soft biorobotics are highlighted.     

一种新型的表面用吡啶修饰的CdS纳米粒子电解质

本文用反胶束方法合成了表面修饰吡啶（Ｐｙ）的ＣｄＳ纳米粒子,由于粒子表面富Ｃｄ＾２＋和表面修饰剂为电中性分子,导致粒子周围吸附反离子作为平衡电荷,这种复合ＣｄＳ纳米粒子在稀溶液中具有类强电解质的电导行为。     

Distributed Electric Field Induces Orientations of Nanosheets to Prepare Hydrogels with Elaborate Ordered Structures and Programmed Deformations

Living organisms use musculatures with spatially distributed anisotropic structures to actuate deformations and locomotion with fascinating functions. Replicating such structural features in artificial materials is of great significance yet remains a big challenge. Here, a facile strategy is reported to fabricate hydrogels with elaborate ordered structures of nanosheets (NSs) oriented under a distributed electric field. Multiple electrodes are distributed with various arrangements in the precursor solution containing NSs and gold nanoparticles. A complex electric field induces sophisticated orientations of the NSs that are permanently inscribed by subsequent photo-polymerization. The resultant anisotropic nanocomposite poly(N-isopropylacrylamide) hydrogels exhibit rapid deformation upon heating or photoirradiation, owing to the fast switching of permittivity of the media and electric repulsion between the NSs. The complex alignments of NSs and anisotropic shape change of discrete regions result in programmed deformation of the hydrogels into various configurations. Furthermore, locomotion is realized by a spatiotemporal light stimulation that locally triggers time-variant shape change of the composite hydrogel with complex anisotropic structures. Such a strategy on the basis of the distributed electric-field-generated ordered structures should be applicable to gels, elastomers, and thermosets loaded with other anisotropic particles or liquid crystals, for the design of biomimetic/bioinspired materials with specific functionalities.