Direct injection of cell‐laden hydrogels shows high potential for tissue regeneration in translational therapy. The traditional cell‐laden hydrogels are often used as bulk space fillers to tissue ...defects after injection, likely limiting their structural controllability. On the other hand, patterned cell‐laden hydrogel constructs often necessitate invasive surgical procedures. To overcome these problems, herein, a unique strategy is reported for encapsulating living human cells in a pore‐forming gelatin methacryloyl (GelMA)‐based bioink to ultimately produce injectable hierarchically macro‐micro‐nanoporous cell‐laden GelMA hydrogel constructs through 3D extrusion bioprinting. The hydrogel constructs can be fabricated into various shapes and sizes that are defect‐specific. Due to the hierarchically macro‐micro‐nanoporous structures, the cell‐laden hydrogel constructs can readily recover to their original shapes, and sustain high cell viability, proliferation, spreading, and differentiation after compression and injection. In addition, in vivo studies further reveal that the hydrogel constructs can integrate well with the surrounding host tissues. These findings suggest that the unique 3D‐bioprinted pore‐forming GelMA hydrogel constructs are promising candidates for applications in minimally invasive tissue regeneration and cell therapy.
An aqueous two‐phase emulsion bioink is used to fabricate a hierarchically macro‐micro‐nanoporous cell‐laden gelatin methacryloyl hydrogel constructs via 3D extrusion bioprinting. A variety of shapes and sizes of the hydrogel constructs can be minimally invasively injected, and readily shape‐recovered to fill irregular defects. The encapsulated cells maintain their viabilities, proliferation, spreading, and differentiation after injection.
Although the technological and scientific importance of functional polymers have been well established over the last few decades, the most recent focus that has attracted much attention concerns ...stimuli-responsive polymer gels. These materials are of particular interest due to their abilities to respond to internal and/or external chemo-physical stimuli. Aside from the scientific challenges of designing stimuli-responsive polymer gels, the main technological interests concern numerous applications, ranging from catalysis in microsystem technology and chemo-mechanical actuators to sensors.
This Special Issue includes seventeen papers covering a wide range of subjects including thermo- and pH-responsive hydrogels, functionalized materials, supramolecular stimuli-responsive structures, composite hydrogels, sensors, and biomedical applications. Together, these contributions not only provide an excellent overview of the current state-of-the-art in the field but also point out exciting challenges and opportunities for future work. In a number of reviews the most recent findings on “Stimuli-Responsive Gels” are compiled in this book supplemented by original contributions
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Injectable conductive hydrogels have great potential as tissue engineering scaffolds and delivery vehicles for electrical signal sensitive cell therapy. In this work, we present the ...synthesis of a series of injectable electroactive degradable hydrogels with rapid self-healing ability and their potential application as cell delivery vehicles for skeletal muscle regeneration. Self-healable conductive injectable hydrogels based on dextran-graft-aniline tetramer-graft-4-formylbenzoic acid and N-carboxyethyl chitosan were synthesized at physiological conditions. The dynamic Schiff base bonds between the formylbenzoic acid and amine group from N-carboxyethyl chitosan endowed the hydrogels with rapid self-healing ability, which was verified by rheological test. Equilibrated swelling ratio, morphology, mechanical strength, electrochemistry and conductivity of the injectable hydrogels were fully investigated. The self-healable conductive hydrogels showed an in vivo injectability and a linear-like degradation behavior. Two different kinds of cells (C2C12 myoblasts and human umbilical vein endothelial cells (HUVEC)) were encapsulated in the hydrogels by self-healing effect. The L929 fibroblast cell culture results indicated the biocompatibility of the hydrogels. Moreover, the C2C12 myoblast cells were released from the conductive hydrogels with a linear-like profile. The in vivo skeletal muscle regeneration was also studied in a volumetric muscle loss injury model. All these data indicated that these biodegradable self-healing conductive hydrogels are potential candidates as cell delivery vehicles and scaffolds for skeletal muscle repair.
Injectable hydrogels with self-healing and electrical conductivity properties are excellent candidates as tissue-engineered scaffolds for myoblast cell therapy and skeletal muscle regeneration. The self-healing property of these hydrogels can prolong their lifespan. However, most of the reported conductive hydrogels are not degradable or do not have the self-healing ability. Herein, we synthesized antibacterial conductive self-healing hydrogels as a cell delivery carrier for cardiac cell therapy based on chitosan-grafted-tetraaniline hydrogels synthesized in our previous work. However, an acid solution was used to dissolve the polymers in that study, which may induce toxicity to cells. In this work, we synthesized a series of injectable electroactive biodegradable hydrogels with rapid self-healing ability composed of N-carboxyethyl chitosan (CECS) and dextran-graft-aniline oligomers, and these hydrogel precusor can dissolve in PBS solution of pH 7.4; we further demonstrated their potential application as cell delivery vehicles for skeletal muscle regeneration.
This study aimed to design a novel thermoreversible compact self-assembled host macromolecule based on beta-cyclodextrin and low molecular weight ethylene glycol with a difunctional guest molecule ...i.e. poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) tri-block co-polymer (Pluronic® 127) through host-guest inclusion complexation in aqueous media using cold method. The injectable thermoreversible self-assembled supramolecular hydrogel was developed to encapsulate hydrophobic curcumin as anti-malignant agent and for controlled delivery to systemic circulation after in vivo application through subcutaneous route. As reversible supramolecular assembly, the thermoresponsive gels showed a unique structure-related reversible gel to sol transition above and below LCST determined via tube titling method. The rheological measurements of the supramolecular hydrogels showed a viscoelastic structure. Optical transmittance of supramolecular assembly also confirmed the thermoreversible sol-gel transitions. The strong potential of supramolecular assembly as injectable controlled delivery was assessed using curcumin as model active pharmaceutical ingredient for in vitro release experiments. The release experiments conducted in various dissolution medias and at different temperature programs showed maximum curcumin release in phosphate buffer solution (7.4) at 35 °C. methyl thiazolyl tetrazolium assay was used to assess the safety and efficacy of self-assembled supramolecular injectable hydrogels. In vitro cytotoxicity study showed that blank supramolecular gels are non-toxic to the L929 cells. While curcumin released from supramolecular injectable hydrogels (Cur-beta-CD/EG-PF127) has the ability to show pharmacological activity and kill the cancer cells. Furthermore the formation of channel type inclusion complex was studied through Fourier transformed infra-red spectroscopy, X-ray diffraction, thermogravimetric analysis, differential scanning calorimetric and scanning electron microscopic analysis.
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Injectable hydrogels with multistimuli responsiveness to electrical field and pH as a drug delivery system have been rarely reported. Herein, we developed a series of injectable ...conductive hydrogels as “smart” drug carrier with the properties of electro-responsiveness, pH-sensitivity, and inherent antibacterial activity. The hydrogels were prepared by mixing chitosan-graft-polyaniline (CP) copolymer and oxidized dextran (OD) as a cross-linker. The chemical structures, morphologies, electrochemical property, swelling ratio, conductivity, rheological property, in vitro and in vivo biodegradation, and gelation time of hydrogels were characterized. The pH-responsive behavior was verified by drug release from hydrogels in PBS solutions with different pH values (pH = 7.4 or 5.5) in an in vitro model. As drug carriers with electric-driven release, the release rate of the model drugs amoxicillin and ibuprofen loaded within CP/OD hydrogels dramatically increased when an increase in voltage was applied. Both chitosan and polyaniline with inherent antibacterial properties endowed the hydrogels with excellent antibacterial properties. Furthermore, cytotoxicity tests of the hydrogels using L929 cells confirmed their good cytocompatibility. The in vivo biocompatibility of the hydrogels was verified by H&E staining. Together, all these results suggest that these injectable pH-sensitive conductive hydrogels with antibacterial activity could be ideal candidates as smart drug delivery vehicles for precise doses of medicine to meet practical demand.
Stimuli-responsive or “smart” hydrogels have attracted great attention in the field of biotechnology and biomedicine, especially on designing novel drug delivery systems. Compared with traditional implantable electronic delivery devices, the injectable hydrogels with electrical stimuli not only are easy to generate and control electrical field but also could avoid frequent invasive surgeries that offer a new avenue for chronic diseases. In addition, designing a drug carrier with pH-sensitive property could release drug efficiently in targeted acid environment, and it could reinforce the precise doses of medicine. Furthermore, caused by opportunistic microorganisms and rapid spread of antibiotic-resistant microbes, infection is still a serious threat for many clinical utilities. To overcome these barriers, we designed a series of injectable antibacterial conductive hydrogels based on chitosan-graft-polyaniline (CP) copolymer and oxidized dextran (OD), and we demonstrated their potential as “smart” delivery vehicles with electro-responsiveness and pH-responsive properties for triggered and localized release of drugs.
Light guiding and manipulation in photonics have become ubiquitous in events ranging from everyday communications to complex robotics and nanomedicine. The speed and sensitivity of light–matter ...interactions offer unprecedented advantages in biomedical optics, data transmission, photomedicine, and detection of multi‐scale phenomena. Recently, hydrogels have emerged as a promising candidate for interfacing photonics and bioengineering by combining their light‐guiding properties with live tissue compatibility in optical, chemical, physiological, and mechanical dimensions. Herein, the latest progress over hydrogel photonics and its applications in guidance and manipulation of light is reviewed. Physics of guiding light through hydrogels and living tissues, and existing technical challenges in translating these tools into biomedical settings are discussed. A comprehensive and thorough overview of materials, fabrication protocols, and design architectures used in hydrogel photonics is provided. Finally, recent examples of applying structures such as hydrogel optical fibers, living photonic constructs, and their use as light‐driven hydrogel robots, photomedicine tools, and organ‐on‐a‐chip models are described. By providing a critical and selective evaluation of the field's status, this work sets a foundation for the next generation of hydrogel photonic research.
The current panorama of hydrogel‐based photonics and advances in fabrication techniques toward functional optical architectures are reviewed, evaluating their capabilities in the biomedical field. Further, the future potential for hydrogel photonic constructs to integrate into live tissues, advanced biosensing platforms, microrobotics, photomedicine, and lab‐on‐chip technologies are discussed.
Gelatin methacryloyl (GelMA) is a versatile material for a wide range of bioapplications. There is an intense interest in developing effective chemical strategies to prepare GelMA with a high degree ...of batch-to-batch consistency and controllability in terms of methacryloyl functionalization and physiochemical properties. Herein, we systematically investigated the batch-to-batch reproducibility and controllability of producing GelMA (target highly and lowly substituted versions) via a one-pot strategy. To assess the GelMA product, several parameters were evaluated, including the degree of methacryloylation, secondary structure, and enzymatic degradation, along with the mechanical properties and cell viability of GelMA hydrogels. The results showed that two types of target GelMA with five batches exhibited a high degree of controllability and reproducibility in compositional, structural, and functional properties owing to the highly controllable one-pot strategy.
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