Schiff base, an important family of reaction in click chemistry, has received significant attention in the formation of self-healing hydrogels in recent years. Schiff base reversibly reacts even in ...mild conditions, which allows hydrogels with self-healing ability to recover their structures and functions after damages. Moreover, pH-sensitivity of the Schiff base offers the hydrogels response to biologically relevant stimuli. Different types of Schiff base can provide the hydrogels with tunable mechanical properties and chemical stabilities. In this review, we summarized the design and preparation of hydrogels based on various types of Schiff base linkages, as well as the biomedical applications of hydrogels in drug delivery, tissue regeneration, wound healing, tissue adhesives, bioprinting, and biosensors.
An injectable, self‐healing hydrogel (≈1.5 kPa) is developed for healing nerve‐system deficits. Neurosphere‐like progenitors proliferate in the hydrogel and differentiate into neuron‐like cells. In ...the zebrafish injury model, the central nervous system function is partially rescued by injection of the hydrogel and significantly rescued by injection of the neurosphere‐laden hydrogel. The self‐healing hydrogel may thus potentially repair the central nervous system.
Hydrogels, which are crosslinked polymer networks with high water contents and rheological solid-like properties, are attractive materials for biomedical applications. Self-healing hydrogels are ...particularly interesting because of their abilities to repair the structural damages and recover the original functions, similar to the healing of organism tissues. In addition, self-healing hydrogels with shear-thinning properties can be potentially used as the vehicles for drug/cell delivery or the bioinks for 3D printing by reversible sol-gel transitions. Therefore, self-healing hydrogels as biomedical materials have received a rapidly growing attention in recent years. In this paper, synthesis methods and repair mechanisms of self-healing hydrogels are reviewed. The biomedical applications of self-healing hydrogels are also described, with a focus on the potential therapeutic applications verified through
experiments. The trends indicate that self-healing hydrogels with automatically reversible crosslinks may be further designed and developed for more advanced biomedical applications in the future.
The immunological response of macrophages to physically produced pure Au and Ag nanoparticles (NPs) (in three different sizes) is investigated in vitro. The treatment of either type of NP at ≥10 ppm ...dramatically decreases the population and increases the size of the macrophages. Both NPs enter the cells but only AuNPs (especially those with smaller diamter) up‐regulate the expressions of proinflammatory genes interlukin‐1 (IL‐1), interlukin‐6 (IL‐6), and tumor necrosis factor (TNF‐α). Transmission electron microscopy images show that AuNPs and AgNPs are both trapped in vesicles in the cytoplasma, but only AuNPs are organized into a circular pattern. It is speculated that part of the negatively charged AuNPs might adsorb serum protein and enter cells via the more complicated endocytotic pathway, which results in higher cytotoxicity and immunological response of AuNPs as compared to AgNPS.
Physically produced gold nanoparticles are more cytotoxic and provoke a larger immunological response in macrophages than silver nanoparticles. This may be due to receptor‐mediated endocytosis (see image).
Adding cellulose nanofibers (CNFs) into waterborne polyurethane (PU) nanoparticle dispersion during synthesis successfully generated high viscosity and directly printable PU/CNF composite ink, ...possibly through the formation of “skewer-like” structure. The 3D printed PU/CNF scaffolds had stable dimensions before and after water removal. Solid scaffolds could be obtained after freeze-drying or by soaking and air dry. The composite scaffolds retained the shape and mechanical integrity during degradation, and maintained the proliferation of fibroblasts over a week.
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•A directly printable waterborne PU composite ink is prepared by introducing CNFs.•CNFs link multiple PU nanoparticles to form skewer structure to increase viscosity.•Direct 3D printing is achieved by particle aggregation at low temperatures.•The printed constructs are hand-holdable and do not melt in 37 °C water.
Waterborne polyurethane (PU) is a green, high performance elastomer but the viscosity of the dispersion is generally too low for direct three-dimensional (3D) printing. Composite brings additional properties while reinforcing the substrate. In the study, printable PU composites were successfully prepared by introducing cellulose nanofibrils (CNFs) and the viscosity was effectively regulated by the amount of neutralizing agent during in-situ synthesis. Rheological measurements supported the good printability. TEM images revealed that CNFs linked multiple PU nanoparticles to form a ‘skewer’ structure. PU/CNF scaffolds were 3D-printed with excellent pattern fidelity and structure stability. Meanwhile, the compression modulus was much higher than the scaffolds printed with a water-soluble viscosity enhancer (PEO). Fibroblasts kept proliferating in the scaffolds for two weeks. The interaction between CNF and PU may offer a novel and unique way to tune the viscosity of waterborne PU for direct 3D printing and enhance the properties of the green elastomers.
Stroke is a common disease with high mortality worldwide. The endogenous neural regeneration during the intracerebral hemorrhage (ICH) stroke is restricted by the brain cavity, inflammation, cell ...apoptosis, and neural scar formation. Biomaterials serving as temporary supporting matrices are highly demanded as injectable implants for brain tissue regeneration. Herein, a chitosan micellar self‐healing hydrogel (CM hydrogel) with comparable modulus (≈150 Pa) to brain, shape adaptability, and proper swelling (≈105%) is developed from phenolic chitosan (PC) and a micellar crosslinker (DPF). Two model drugs are individually packaged in the hydrophilic network and hydrophobic micelle cavities of CM hydrogel, and they feature asynchronous releasing kinetics, including a first‐order rapid release for hydrophilic drug and a zero‐order sustained release for hydrophobic drug. The dual‐drug loaded CM (CMD) hydrogel delivers two clinical drugs corresponding to the anti‐inflammatory and neurogenesis phases of the stroke to ICH rats through brain injection. The rats receiving CMD hydrogel show behavioral improvement (≈84% recovery) and balanced brain midline shift (≈0.98 left/right hemibrain ratio). Immunohistochemistry reveals neurogenesis (doublecortin‐ and nestin‐ positive cells) and evidence of angiogenesis (≈18 µm diameter vessels lined with CD31‐positive cells). The injectable CMD hydrogel offers a novel asynchronous drug delivery platform for treating ICH stroke.
A chitosan self‐healing hydrogel with comparable modulus to brain tissue, shape adaptability, and dual drug‐encapsulating capacity is implemented to treat the intracerebral hemorrhage stroke rats. The hydrogel exhibits asynchronous drug release kinetics aligned with the therapeutic requirement in different stages of intricate stroke pathologies. The positive efficacy of the hydrogel treatment is confirmed by behavioral, histological, and image analyses.
Conductive hydrogel, with electroconductive properties and high water content in a three-dimensional structure is prepared by incorporating conductive polymers, conductive nanoparticles, or other ...conductive elements, into hydrogel systems through various strategies. Conductive hydrogel has recently attracted extensive attention in the biomedical field. Using different conductivity strategies, conductive hydrogel can have adjustable physical and biochemical properties that suit different biomedical needs. The conductive hydrogel can serve as a scaffold with high swelling and stimulus responsiveness to support cell growth in vitro and to facilitate wound healing, drug delivery and tissue regeneration in vivo. Conductive hydrogel can also be used to detect biomolecules in the form of biosensors. In this review, we summarize the current design strategies of conductive hydrogel developed for applications in the biomedical field as well as the perspective approach for integration with biofabrication technologies.
Tissue engineering biomaterials are aimed to mimic natural tissue and promote new tissue formation for the treatment of impaired or diseased tissues. Highly porous biomaterial scaffolds are often ...used to carry cells or drugs to regenerate tissue-like structures. Meanwhile, self-healing hydrogel as a category of smart soft hydrogel with the ability to automatically repair its own structure after damage has been developed for various applications through designs of dynamic crosslinking networks. Due to flexibility, biocompatibility, and ease of functionalization, self-healing hydrogel has great potential in regenerative medicine, especially in restoring the structure and function of impaired neural tissue. Recent researchers have developed self-healing hydrogel as drug/cell carriers or tissue support matrices for targeted injection via minimally invasive surgery, which has become a promising strategy in treating brain diseases. In this review, the development history of self-healing hydrogel for biomedical applications and the design strategies according to different crosslinking (gel formation) mechanisms are summarized. The current therapeutic progress of self-healing hydrogels for brain diseases is described as well, with an emphasis on the potential therapeutic applications validated by in vivo experiments. The most recent aspect as well as the design rationale of self-healing hydrogel for different brain diseases is also addressed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Electroconductive hydrogels and scaffolds have great potential for strain sensing and in tissue engineering. Herein, we designed electroconductive self-healing hydrogels and shape-recoverable ...scaffolds with injectability, strain/motion-sensing ability, and neural regeneration capacity. The crosslinked network of hydrogels and scaffolds was synthesized and prepared under physiological conditions from N-carboxyethyl chitosan (CEC), a chitosan-modified polypyrrole (DCP) nanoparticle (∼40 nm), and a unique aldehyde-terminated difunctional polyurethane (DFPU) crosslinker. CEC was mixed with DCP by electrostatic interaction and then crosslinked with DFPU through a dynamic Schiff base reaction. Schiff base endowed the hydrogels with self-healing behavior, confirmed by rheological examinations. Shape-recoverable scaffolds were obtained by freeze-drying the hydrogels. These hydrogels and scaffolds showed injectability and conductivity (3–6 mS/cm), while the scaffolds also exhibited high water absorption and durable elasticity after repeated deformation. The hydrogels and scaffolds promoted the attachment, proliferation, and differentiation of neural stem cells (NSCs). The scaffolds had excellent strain/motion-sensing properties in vitro and ex vivo as well as biodegradability and biocompatibility in vivo. Moreover, the neural regeneration capacity of the conductive hydrogel or the cell-laden conductive hydrogel was demonstrated by the rescue of motor function (∼53 and ∼80% functional recoveries, respectively) in the zebrafish brain injury model. These hydrogels and scaffolds are potential candidates for nerve repair and motion sensing.
Abstract The 3D bioprinting technology serves as a powerful tool for building tissue in the field of tissue engineering. Traditional 3D printing methods involve the use of heat, toxic organic ...solvents, or toxic photoinitiators for fabrication of synthetic scaffolds. In this study, two thermoresponsive water-based biodegradable polyurethane dispersions (PU1 and PU2) were synthesized which may form gel near 37 °C without any crosslinker. The stiffness of the hydrogel could be easily fine-tuned by the solid content of the dispersion. Neural stem cells (NSCs) were embedded into the polyurethane dispersions before gelation. The dispersions containing NSCs were subsequently printed and maintained at 37 °C. The NSCs in 25–30% PU2 hydrogels (∼680–2400 Pa) had excellent proliferation and differentiation but not in 25–30% PU1 hydrogels. Moreover, NSC-laden 25–30% PU2 hydrogels injected into the zebrafish embryo neural injury model could rescue the function of impaired nervous system. However, NSC-laden 25–30% PU1 hydrogels only showed a minor repair effect in the zebrafish model. In addition, the function of adult zebrafish with traumatic brain injury was rescued after implantation of the 3D-printed NSC-laden 25% PU2 constructs. Therefore, the newly developed 3D bioprinting technique involving NSCs embedded in the thermoresponsive biodegradable polyurethane ink offers new possibilities for future applications of 3D bioprinting in neural tissue engineering.
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