Hydrogels and Hydrogel-related Healing Materials

This review highlights the recent advances in fluorescence microscopic visualization of synthetic hydrogels, bio-macromolecular hydrogels, organohydrogels, and supramolecular hydrogels. Topics related to the structural changes of hydrogels, hydrogel mechanics, and super-resolution imaging of hydrogels based on fluorescence microscopy are introduced. The design concepts, imaging mechanisms, and potential applications of the novel fluorescence visualization strategies are discussed in detail. Finally, our opinions on the major challenges of current research, possible solutions, and future directions are shared.

This review describes an overview of the strategies used to prepare self-healing and self-restoring materials utilizing reversible and movable crosslinks. Reversible crosslinks, consisting of noncovalent bonds, can reversibly undergo repeated cleavage and reformation. Therefore, self-healing can be achieved by effectively regenerating reversible crosslinks between polymeric chains. Movable crosslinks consist of polymer chains that penetrate macrocyclic units and have self-restoring properties due to their sliding motion along the polymeric chains. Self-restoring materials can regain their original shape and mechanical properties after a cycle of loading and unloading external stress.

Various changes occur in the myocardial infarcted microenvironment. An in-depth understanding of these changes has enabled the development of the functional hydrogels for cardiac repair. This article introduces recent advance in functional hydrogels for the treatment of myocardial infarction, including MMP-responsive hydrogels, ROS-scavenging hydrogels, immunomodulatory hydrogels, conductive hydrogels, vascularized hydrogels, and 3D printed hydrogels. Future perspective is also presented.

The “molecular knitting method” improves toughness and Young’s modulus. We prepared dual cross-network (DC) elastomers with a knitting structure and single movable cross-network elastomers with penetrating polymers (SCP elastomers) by swelling the single movable cross-network (SC) elastomers in liquid monomers. The DC elastomers showed a high toughness and a high Young’s modulus. SAXS indicated that the DC elastomers exhibited heterogeneity at the nanoscale. The DC elastomers showed a significantly broader relaxation time distribution than the SC and SCP elastomers. Thus, the nanoscale heterogeneity and broader relaxation time distribution were important to increase toughness.

Clay nanosheets (CNSs) of synthetic hectorite have been used for synthesizing advanced functional gels that exhibit high mechanical toughness and many unprecedented characteristics, such as cell harvesting, instant strong adhesion, and self-healing. Upon varying the pH and salt concentration, the aqueous CNS dispersions were found to exhibit a maximum viscosity accompanied by gelation, in addition to large and complex time-dependent viscosity changes in the static state. Such anomalous viscosity dynamics depended on the types of clay and acid (salt), temperature, number of repetitions, and agitation conditions; their mechanisms were also discussed in terms of variations in the CNS microstructures.

A multifunctional plasmonic nanoplatform inspired from chameleon skin is developed for the purpose of glucose sensing applications in body fluids. Fabricated nanoplatforms consisted of two outer layers of fully-crosslinked P(NIPAAm-co-NIPMAAm) hydrogel embedded with plasmonic silver nanocubes, while the inner layer is an electrospun nanofibrous mat of PCL/PEO. Morphological and optical investigation on layers of the platform as well as the whole structure shows the well-fabricated structure offering a compact and stable device. The platform provides fast photothermal-responsivity, mechanical and antibacterial properties as well as sensing features, which can be used to anticipate glucose levels in body fluids in both ranges of healthy and diabetic.

We controlled the oscillatory behaviors of the comb-type self-oscillating gels by varying the properties of the grafted chain. The grafted chain was introduced by ATRP (atom-transfer radical polymerization) as a “grafting from” method. We demonstrated that controlling the length of the grafted chains and the amount of Ru(bpy)₃ in the grafted chain can lead to the controlled amplitude, swelling rate and deswelling rate during the BZ reaction.

Versatile ionic gelatin-glycerol hydrogel for soft sensing applications: The sensing device is inexpensive and easy to manufacture, is self-healable at room temperature, can undergo strains of up to 454%, presents stability over long periods of time, and is biocompatible and biodegradable. This material is ideal for strain sensing applications, with a linear correlation coefficient R² = 0.9971 and a pressure-insensitive conduction mechanism. The experimental results show the applicability of ionic hydrogels for wearable devices and soft robotic technologies for strain, humidity and temperature sensing while being able to partially self-heal at room temperature.

We report dual-stimuli responsive and injectable hydrogels comprising a highly biocompatible cartilage acellularized matrix (CAM) and a water-soluble diselenide cross-linker, formed by ultrafast IEDDA click chemistry. The diselenide crosslinker was synthesized to have two PEG spacers and two tetrazine moieties. The PEG spacers enhanced the solubility of the crosslinker, whereas tetrazine functionalities reacted with norbornene groups of CAM during loading of DOX an ICG in hydrogels. The diselenide linkages could be cleaved internally by an over-expressed GSH tumor biomarker (a reducing molecule) or externally by NIR-light irradiation, releasing DOX which eradicated a tumor.

A mouse model of laminectomy is established to study the process of epidural fibrosis. Neutrophils infiltrated into the wound area release neutrophil extracellular traps (NETs). The temperature-sensitive hydrogel loaded with DNase I not only provide a perfect physical barrier but also destroy NETs via the encapsulated DNase I, thereby alleviating the excessive fibrosis following spine operations.

Sustained and controllable local gene therapy is a potential method for treating osteoarthritis (OA). Here, monodisperse gelatin methacryloyl microspheres produced under one-step innovative microfluidic technology were applied to construct “nano-micron” combined gene hydrogel by absorbing gene nanoparticles consisting of microRNA-140 and multifunctional gene vectors, arginine, histidine, and phenylalanine-modified generation 5 polyamidoamine (named G5-AHP). The “nano-micron” combined gene hydrogel showed better injectability in sustainable and matrix metalloproteinases-responsive degradation methods and provided a novel cell-free approach to alleviate the progression of OA.

Schematic illustration of functional injectable hydrogel system for cartilage regeneration. (1) Preparation of hydrogel with the function for spatiotemporal releasing SDF-1 and KGN; (2) Spatiotemporal regulation of MSCs recruitment and chondrogenic differentiation by hydrogel in vitro; (3) Implantation of hydrogel and cartilage regeneration.

Potassium acetate (KAc) has desirably both a high solubility and a salting-out effect on polyvinyl alcohol (PVA). The freezing temperature of 50 wt% KAc solution can reach as low as −70 °C. The hydrogels soaked in 50 wt% KAc solution exhibit the highest mechanical properties with an ultimate stress of 8.2 MPa and toughness of 25.8 MJ/m³, surpassing most reported results for anti-freezing gels. At 50 wt% KAc, the hydrogels also present a high conductivity of 8.0 S/m at room temperature and 1.2 S/m at −60 °C.