A Cyclical Magneto-Responsive Massage Dressing for Wound Healing.

Tissue development is mediated by a combination of mechanical and biological signals. Currently, there are many reports on biological signals regulating repair. However, insufficient attention is paid to the process of mechanical regulation, especially the active mechanical regulation in vivo, which has not been realized. Herein, a novel dynamically regulated repair system for both in vitro and in vivo applications is developed, which utilizes magnetic nanoparticles as non-contact actuators to activate hydrogels. The magnetic hydrogel can be periodically activated and deformed to different amplitudes by a dynamic magnetic system. An in vitro skin model is used to explore the impact of different dynamic stimuli on cellular mechano-transduction signal activation and cell differentiation. Specifically, the effect of mechanical stimulation on the phenotypic transition of fibroblasts to myofibroblasts is investigated. Furthermore, in vivo results verify that dynamic massage can simulate and enhance the traction effect in skin defects, thereby accelerating the wound healing process by promoting re-epithelialization and mediating dermal contraction.

Hydrogel Rivet with Unidirectional Shape Morphing for Flexible Mechanical Assembly.

Integrating diverse materials and functions into highly additive produce has piqued global interest due to the increasing demands of intelligent soft robotics. Nevertheless, existing assembly techniques, especially supramolecular assembly which heavily rely on precise chemical design and specific recognition, may prove inadequate when confronted with diverse external demands. Inspired by the traditional mechanical assembly, rivet connection, herein, a thermo-responsive hydrogel with unidirectional shape-morphing is fabricated and a stable mechanical assembly is constructed by emulating the rivet connection mechanism. This system employed poly(acrylamide-co-acrylic acid) [P(AAm-co-AAc)] to induce continuous swelling and hexylamine-modified polyvinyl alcohol (PVA-C6) as a molecular switch to control the swelling process. The hydrogel rivet, initially threaded through pre-fabricated hollows in two components. Subsequently, upon the disassociation of alkane chains the molecular switch would activate, inducing swelling and stable mechanical assembly via anchor structures. Moreover, to enhance the assembly strength, knots are introduced to enhance assembly strength, guiding localized stress release for programmed deformations. Additionally, the system can be remotely controlled using near-infrared light (NIR) by incorporating photo-thermal nanoparticles. This work presents a universal and efficient strategy for constructing stable mechanical assemblies without compromising overall softness, offering significant potential for the fabrication of integrated soft robots.

Smart photonic crystal hydrogels for visual glucose monitoring in diabetic wound healing.

Diabetes is a global chronic disease that seriously endangers human health and characterized by abnormally high blood glucose levels in the body. Diabetic wounds are common complications which associate with impaired healing process. Biomarkers monitoring of diabetic wounds is of great importance in the diabetes management. However, actual monitoring of biomarkers still largely relies on the complex process and additional sophisticated analytical instruments. In this work, we prepared hydrogels composed of different modules, which were designed to monitor different physiological indicators in diabetic wounds, including glucose levels, pH, and temperature. Glucose monitoring was achieved based on the combination of photonic crystal (PC) structure and glucose-responsive hydrogels. The obtained photonic crystal hydrogels (PCHs) allowed visual monitoring of glucose levels in physiological ranges by readout of intuitive structural color changes of PCHs during glucose-induced swelling and shrinkage. Interestingly, the glucose response of double network PCHs was completed in 15 min, which was twice as fast as single network PCHs, due to the higher volume fraction of glucose-responsive motifs. Moreover, pH sensing was achieved by incorporation of acid-base indicator dyes into hydrogels; and temperature monitoring was obtained by integration of thermochromic powders in hydrogels. These hydrogel modules effectively monitored the physiological levels and dynamic changes of three physiological biomarkers, both in vitro and in vivo during diabetic wound healing process. The multifunctional hydrogels with visual monitoring of biomarkers have great potential in wound-related monitoring and treatment.

A minimally disruptive method for measuring water potential in planta using hydrogel nanoreporters.

Leaf water potential is a critical indicator of plant water status, integrating soil moisture status, plant physiology, and environmental conditions. There are few tools for measuring plant water status (water potential) in situ, presenting a critical barrier for developing appropriate phenotyping (measurement) methods for crop development and modeling efforts aimed at understanding water transport in plants. Here, we present the development of an in situ, minimally disruptive hydrogel nanoreporter (AquaDust) for measuring leaf water potential. The gel matrix responds to changes in water potential in its local environment by swelling; the distance between covalently linked dyes changes with the reconfiguration of the polymer, leading to changes in the emission spectrum via Förster Resonance Energy Transfer (FRET). Upon infiltration into leaves, the nanoparticles localize within the apoplastic space in the mesophyll; they do not enter the cytoplasm or the xylem. We characterize the physical basis for AquaDust's response and demonstrate its function in intact maize (Zea mays L.) leaves as a reporter of leaf water potential. We use AquaDust to measure gradients of water potential along intact, actively transpiring leaves as a function of water status; the localized nature of the reporters allows us to define a hydraulic model that distinguishes resistances inside and outside the xylem. We also present field measurements with AquaDust through a full diurnal cycle to confirm the robustness of the technique and of our model. We conclude that AquaDust offers potential opportunities for high-throughput field measurements and spatially resolved studies of water relations within plant tissues.

Development and In Vitro characterization of Azadirachta Indica Gum grafted polyacrylamide Based pH-Sensitive Hydrogels to improve the Bioavailability of Lansoprazole.

The present study intended to develop a pH-responsive hydrogel based on Neem gum (Ng) to improve Lansoprazole (LSP) oral bioavailability. pH-responsive hydrogel formulations (F1-F9) were prepared using different Ng ratios, Acrylamide (AAm), and methylene-bis-acrylamide (MBA). The formulated hydrogels were characterized through FTIR, thermal analysis, swelling ratio, SEM, sol-gel ratios, In-Vitro drug release, and cytotoxicity analysis. Azadirachta Indica was extracted to produce a powder containing 21.5 % Ng. Prepared hydrogels showed maximum swelling at pH 7.4, whereas the swelling at an acidic pH was insignificant. LSP-loaded hydrogel demonstrated a regulated release of LSP for up to 24 h and indicated a Super Case II transport release mechanism. During the cytotoxic evaluation, the delivery system showed minimal cytotoxicity towards normal cells, while percent cytotoxicity was carried out for a longer duration (up to 96 h). The present study revealed Azadirachta indica gum-based pH-responsive hydrogel as a promising technique for precisely delivering LSP.

A portable intelligent hydrogel platform for multicolor visual detection of HAase.

Hyaluronidase (HAase) is an important endoglycosidase involved in numerous physiological and pathological processes, such as apoptosis, senescence, and cancer progression. Simple, convenient, and sensitive detection of HAase is important for clinical diagnosis. Herein, an easy-to-operate multicolor visual sensing strategy was developed for HAase determination. The proposed sensor was composed of an enzyme-responsive hydrogel and a nanochromogenic system (gold nanobipyramids (AuNBPs)). The enzyme-responsive hydrogel, formed by polyethyleneimine-hyaluronic acid (PEI-HA), was specifically hydrolyzed with HAase, leading to the release of platinum nanoparticles (PtNPs). Subsequently, PtNPs catalyzed the mixed system of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 to produce TMB2+ under acidic conditions. Then, TMB2+ effectively etched the AuNBPs and resulted in morphological changes in the AuNBPs, accompanied by a blueshift in the localized surface plasmon resonance peak and vibrant colors. Therefore, HAase can be semiquantitatively determined by directly observing the color change of AuNBPs with the naked eye. On the basis of this, the method has a linear detection range of HAase concentrations between 0.6 and 40 U/mL, with a detection limit of 0.3 U/mL. In addition, our designed multicolor biosensor successfully detected the concentration of HAase in human serum samples. The results showed no obvious difference between this method and enzyme-linked immunosorbent assay, indicating the good accuracy and usability of the suggested method.

Thermo-Responsive Hydrogel Containing Microfluidic Chitosan Nanoparticles Loaded with Opuntia ficus-indica Extract for Periodontitis Treatment.

Periodontitis is a chronic inflammatory disease resulting from the dysbiosis of periodontal bacteria and the host's immune response, leading to tissue degradation and sustained inflammation. Traditional treatments, such as mechanical debridement and antimicrobial agents, often fail to fully eradicate pathogenic bacteria, especially in deep periodontal pockets. Consequently, the need for novel therapeutic approaches has increased the interest in bioactive natural extracts, such as that of Opuntia ficus-indica, known for its anti-inflammatory, antioxidant, and antimicrobial properties. This study investigates the encapsulation of Opuntia ficus-indica extract in OFI-loaded chitosan nanoparticles (OFI-NPs) via ionotropic gelation using a microfluidic system, allowing precise control over nanoparticle characteristics and enhancing protection against enzymatic degradation. To achieve localized and sustained release in periodontal pockets, a thermo-responsive hydrogel comprising hyaluronic acid and Pluronic F127 (OFI@tgels) was developed. The transition of OFI@tgels from a solution at low temperatures to a solid at body temperature enables prolonged drug release at inflammation sites. The in vitro application of the optimized formulation eradicated biofilms of S. mutans, P. aeruginosa (PAO1), and P. gingivalis over 36 h and disrupted extracellular polymeric substance formation. Additionally, OFI@tgel modulated immune responses by inhibiting M1 macrophage polarization and promoting a shift to the M2 phenotype. These findings suggest that OFI@tgel is a promising alternative treatment for periodontitis, effectively reducing biofilm formation and modulating the immune response.

Dual-Stimuli Cooperative Responsive Hydrogel Microactuators Via Two-Photon Lithography.

With the development of bionics as well as materials science, intelligent soft actuators have shown promising applications in many fields such as soft robotics, sensing, and remote manipulation. Microfabrication technologies have enabled the reduction of the size of responsive soft actuators to the micron level. However, it is still challenging to construct microscale actuators capable of responding to different external stimuli in complex and diverse conditions. Here, this work demonstrates a dual-stimuli cooperative responsive hydrogel microactuator by asymmetric fabrication via femtosecond laser direct writing. The dual response of the hydrogel microstructure is achieved by employing responsive hydrogel with functional monomer 2-(dimethylamino)ethyl methacrylate. Raman spectra of the hydrogel microstructures suggest that the pH and temperature response of the hydrogel is generated by the changes in tertiary amine groups and hydrogen bonds, respectively. The asymmetric hydrogel microstructures show opposite bending direction when being heated to high temperature or exposed to acid solution, and can independently accomplish the grasp of polystyrene microspheres. Moreover, this work depicts the cooperative response of the hydrogel microactuator to pH and temperature at the same time. The dual-stimuli cooperative responsive hydrogel microactuators will provide a strategy for designing and fabricating controllable microscale actuators with promising applications in microrobotics and microfluidics.

Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is an age-related disease characterised by the accumulation of senescent chondrocytes, which drives its pathogenesis and progression. Senescent cells exhibit distinct features, including mitochondrial dysfunction and the excessive accumulation and release of reactive oxygen species (ROS), which are highly correlated and lead to a vicious cycle of increasing senescent cells. Stem cell therapy has proven effective in addressing cellular senescence, however, it still has issues such as immune rejection and ethical concerns. Microvesicles (MVs) constitute the primary mechanism through which stem cell therapy exerts its effects, offering a cell-free approach that circumvents these risks and has excellent anti-ageing potential. Nonetheless, MVs have a short in vivo half-life, and their secretion composition varies considerably under diverse conditions. This study aims to address these issues by constructing a ROS-responsive hydrogel loaded with pre-stimulant MVs. Through responding to ROS levels this hydrogel intelligently releases MVs, and enhancing mitochondrial function in chondrocytes to improving cellular senescence. RESULT: We employed Interferon-gamma (IFN-γ) as a stem cell-specific stimulus to generate IFN-γ-microvesicles (iMVs) with enhanced anti-ageing effects. Simultaneously, we developed a ROS-responsive carrier utilising 3-aminophenylboronic acid (APBA)-modified silk fibroin (SF) and polyvinyl alcohol (PVA). This carrier served to protect MVs, prolong longevity, and facilitate intelligent release. In vitro experiments demonstrated that the Hydrogel@iMVs effectively mitigated cell senescence, improved mitochondrial function, and enhanced cellular antioxidant capacity. In vivo experiments further substantiated the anti-ageing capabilities of the Hydrogel@iMVs. CONCLUSION: The effect of MVs can be significantly enhanced by appropriate pre-stimulation and constructing a suitable carrier. Therefore, we have developed a ROS-responsive hydrogel containing IFN-γ pre-stimulated iMVs to target the characteristics of ageing chondrocytes in OA for therapeutic purposes. Overall, this novel approach effectively improving mitochondrial dysfunction by regulating the balance between mitochondrial fission and fusion, and the accumulation of reactive oxygen species was reduced, finally, alleviates cellular senescence, offering a promising therapeutic strategy for OA.

Hybrid Vesicles Enable Mechano-Responsive Hydrogel Degradation.

Stimuli-responsive hydrogels are intriguing biomimetic materials. Previous efforts to develop mechano-responsive hydrogels have mostly relied on chemical modifications of the hydrogel structures. Here, we present a simple, generalizable strategy that confers mechano-responsive behavior on hydrogels. Our approach involves embedding hybrid vesicles, composed of phospholipids and amphiphilic block copolymers, within the hydrogel matrix to act as signal transducers. Under mechanical stress, these vesicles undergo deformation and rupture, releasing encapsulated compounds that can control the hydrogel network. To demonstrate this concept, we embedded vesicles containing ethylene glycol tetraacetic acid (EGTA), a calcium chelator, into a calcium-crosslinked alginate hydrogel. When compressed, the released EGTA sequesters calcium ions and degrades the hydrogel. This study provides a novel method for engineering mechano-responsive hydrogels that may be useful in various biomedical applications.

Jammed Microgel-Based Inks for 3D Printing of Complex Structures Transformable via pH/Temperature Variations.

Structure changes mediated by anisotropic volume changes of stimuli-responsive hydrogels are useful for many research fields, yet relatively simple structured objects are mostly used due to limitation in fabrication methods. To fabricate complex 3 dimensional (3D) structures that undergo structure changes in response to external stimuli, jammed microgel-based inks containing precursors of stimuli-responsive hydrogels are developed for extrusion-based 3D printing. Specifically, the jammed microgel-based inks are prepared by absorbing precursors of poly(acrylic acid) or poly(N-isopropylacrylamide) in poly(acrylamide) (PAAm) microgels, and jamming them. The inks exhibit shear-thinning and self-healing properties that allow extrusion of the inks through a nozzle and rapid stabilization after printing. Stimuli-mediated volume changes are observed for the extruded structures when they are post-crosslinked by UV light to form interpenetrating networks of PAAm microgels and stimuli-responsive hydrogels. Using this method, a dumbbell-shaped object that can transform to a biconvex shape, and a gripper that can grasp and lift an object in response to stimuli are 3D-printed. The jammed microgel-based 3D printing strategy is a versatile method useful for variety of applications as diverse types of monomers absorbable in the microgels can be used to fabricate complex 3D objects transformable by external stimuli.

A Multifunctional Light-Driven Swimming Soft Robot for Various Application Scenarios.

The locomotor behavior of creatures in nature can bring a lot of inspiration for the fabrication of soft actuators. In this paper, we fabricated a bionic light-driven swimming soft robot that can perform grasping of tiny objects and achieve the task of object transfer. By adding carbon nanotubes (CNTs), the temperature-sensitive hydrogels can be endowed with light-responsive properties. The fabricated composite hydrogel structure can control the contraction and expansion of volume by light, which is similar to the contraction and diastole behavior of muscles. The oscillation of the fish tail and the grasping action of the normally closed micromanipulator can be achieved by the control of the irradiation of the xenon light source. The bending of the bionic arm can be controlled by the irradiation of a near-infrared (NIR) laser, which transforms the spatial position and posture of the micromanipulator. The proposed scheme is feasible for miniaturized fabrication and application of flexible actuators. This work provides some important insights for the study of light-driven microrobots and light-driven flexible actuators.

Biomacromolecule-Fueled Transient Volume Phase Transition of a Hydrogel.

A metabolic cycle-inspired hydrogel which exhibits the biomacromolecule-fueled transient volume phase transition is reported. This hydrogel has the affinity and digestive capacity for a fuel α-poly-L-lysine by incorporating acrylic acid and trypsin. The hydrogel captured fuel and transiently shrank owing to the construction of electrostatic cross-linkages. This process was inherently connected with the digestion of these cross-linkages and the release of oligo-lysine as waste, which induced the reswelling of the hydrogel at equilibrium. The transient volume change of the hydrogel realized the fuel-stimulated transient release of a payload. This study provides a strategy for engineering materials with biomacromolecule-fueled dynamic functions under the out-of-equilibrium condition.

Synthesis, characterization, and in vitro evaluation of the starch-based α-amylase responsive hydrogels.

Controlled-release drug delivery systems are promising platforms in medicine. Among various types of material in drug delivery, hydrogels are interesting ones. They are water-soluble and tissue compatible polymers with a high capacity to carry and release drugs in a controllable manner. In this study, we introduce the synthesis, characterization, and application of an α-amylase responsive hydrogel in controlled drug delivery. The newly synthesized starch-based hydrogels structurally characterized by means of Fourier-transform infrared spectroscopy and scanning electron microscopy. A proapoptotic drug, doxorubicin, was loaded into the hydrogels and the controlled release of the drug was assessed in the presence of α-amylase and ultimately it was evaluated to controlled-drug release in vitro and subsequently in killing cancer cells. Our results highlight the effectiveness of temporal drug delivery using α-amylase responsive hydrogels in killing cancer cells.

Environmentally responsive hydrogels for repair of cardiovascular tissue.

Cardiovascular diseases (CVDs) pose a serious threat to human health, which are characterized by high disability and mortality rate globally such as myocardial infarction (MI), atherosclerosis, and heart failure. Although stem cells transplantation and growth factors therapy are promising, their low survival rate and loss at the site of injury are major obstacles to this therapy. Recently, the development of hydrogel scaffold materials provides a new way to solve this problem, which have shown the potential to treat CVD. Among these scaffold materials, environmentally responsive hydrogels have great prospects in repairing the microenvironment of cardiovascular tissues and vascular regeneration. They provide a new method for the treatment of cardiovascular tissue repair and space-time control for the release of various therapeutic drugs, including small-molecule drugs, growth factors, and stem cells. Herein, this article reviews the occurrence and current treatment of CVD, as well as the repair of cardiovascular injury by several environmental responsive hydrogels systems currently used, mainly focusing on the delivery of growth factors or the application of cell therapy to revascularization. In addition, we will also discuss the enormous potential and personal perspectives of environmentally responsive hydrogels in cardiovascular repair.

Stimuli-Sensitive Self-Assembled Tubules Based on Lysine-Derived Surfactants for Delivery of Antimicrobial Proteins.

Drug delivery vectors based on amphiphiles have important features such as versatile physicochemical properties and stimuli-responsiveness. Amino acid-based surfactants are especially promising amphiphiles due to their enhanced biocompatibility compared to conventional surfactants. They can self-organize into micelles, vesicles and complex hierarchical structures, such as fibers, twisted and coiled ribbons, and tubules. In this work, we investigated the self-assembly and drug loading properties of a family of novel anionic double-tailed lysine-derived surfactants, with variable degree of tail length mismatch, designated as mLys10 and 10Lysn, where m and n are the number of carbon atoms in the tails. These surfactants form tubular aggregates with assorted morphologies in water that undergo gelation due to dense entanglement, as evidenced by light and electron microscopy. Lysozyme (LZM), an enzyme with antimicrobial properties, was selected as model protein for loading. After the characterization of the interfacial properties and phase behavior of the amphiphiles, the LZM-loading ability of the tubules was investigated, under varying experimental conditions, to assess the efficiency of the aggregates as pH- and temperature-sensitive nanocarriers. Further, the toxicological profile of the surfactants per se and surfactant/LZM hydrogels was obtained, using human skin fibroblasts (BJ-5ta cell line). Overall, the results show that the tubule-based hydrogels exhibit very interesting properties for the transport and controlled release of molecules of therapeutic interest.

Homogeneous photoelectrochemical biosensor for microRNA based on target-responsive hydrogel coupled with exonuclease III and nicking endonuclease Nb.BbvCI assistant cascaded amplification strategy.

MicroRNAs can serve as biomarkers for many cancers, so it is significant to develop simple and sensitive strategies for microRNAs detection. Photoelectrochemical (PEC) detection has the advantages of simple equipment and high sensitivity. But in conventional PEC DNA sensors, tedious immobilization procedures of photoactive materials and capture probes on electrode surfaces are inevitable. To overcome those limitations, a homogeneous PEC biosensor based on target-responsive hydrogels has been developed (miRNA-155 has been chosen as a model target). PEC signal molecules (TiO2 nanoparticles, TiO2 NPs) were embedded in DNA hydrogels formed by hyaluronic acid sodium salt, amine-modified DNA double strands, and polyethylenimine rich in amine groups. In the presence of the target, DNA double strands in hydrogel were nicked by endonuclease and TiO2 NPs were released to the supernate and a high PEC response was obtained when collecting the supernate for PEC test, while almost no TiO2 NPs released in the absence of the target. Thanks to the exonuclease III and nicking endonuclease Nb.BbvCI-assisted cascaded amplification strategy, the proposed biosensor exhibits high sensitivity toward miRNA-155 with a low detection limit of 0.41 fM and a wide linear range from 1.0 fM to 100 pM. Since this method circumvents tedious electrode modification procedures, the proposed technique exhibits the advantages of simplicity and good reproducibility. Moreover, the prepared hydrogels have outstanding storage stability, so that they can be prepared in advance and shorten detection time. This biosensing platform provides a versatile strategy for the construction of homogeneous PEC biosensors for the detection of diverse targets. Photoelectrochemical detection techniques have been coupled with controlled release system to develop an immobilization-free microRNA biosensor. High sensitivity has been realized based on cascaded signal amplification strategy, and the proposed biosensor has been applied to detect the target in real sample with satisfied results. Since no tedious electrode modifications, the proposed homogeneous PEC sensor exhibits high reproducibility and good stability.

Large three-dimensional cell constructs for tissue engineering.

Much research has been conducted on fabricating biomimetic biomaterials in vitro. Tissue engineering approaches are often conducted by combining cells, scaffolds, and growth factors. However, the degradation rate of scaffolds is difficult to control and the degradation byproducts occasionally limit tissue regeneration. To overcome these issues, we have developed a novel system using a thermo-responsive hydrogel that forms scaffold-free, three-dimensional (3D) cell constructs with arbitrary size and morphology. 3D cell constructs prepared using bone marrow-derived stromal stem cells (BMSCs) exhibited self-organizing ability and formed bone-like tissue with endochondral ossification. Endothelial cells were then introduced into the BMSC construct and a vessel-like structure was formed within the constructs. Additionally, the bone formation ability was promoted by endothelial cells and cell constructs could be freeze-dried to improve their clinical application. A pre-treatment with specific protein protectant allowed for the fabrication of novel bone substitutes composed only of cells. This 3D cell construct technology using thermo-responsive hydrogels was then applied to other cell species. Cell constructs composed of dental pulp stem cells were fabricated, and the resulting construct regenerated pulp-like tissue within a human pulpless tooth. In this review, we demonstrate the approaches for the in vitro fabrication of bone and dental pulp-like tissue using thermo-responsive hydrogels and their potential applications.

Rapid photothermal actuation of light-addressable, arrayed hydrogel columns in a macroporous silicon membrane.

This paper presents rapid photothermal actuation of light-addressable, arrayed hydrogel columns in a macroporous silicon membrane. Au nanorods are incorporated into thermo-responsive p-NIPAAm hydrogel to utilize surface plasmon-induced local heating by near-infrared light. By measuring optical transmission through the fabricated membrane structure with Au nanorod embedded hydrogel, we have demonstrated that photothermal actuation of hydrogel can be done in two-dimensional, pixel-like configuration with high spatial and temporal resolutions. Benefiting from the hydrogel volume confinement within micron-sized pores, we have achieved sub-second response time of hydrogel photothermal actuation and its repeatable photothermal actuation on highly localized illuminated area. Considering that each hydrogel column is confined within each pore and different wavelength of light can be used to induce photothermal actuation of hydrogel's deswelling characteristics by modifying physical dimensions of Au nanorods, it has a potential for optically-addressable, multiplexed drug release systems with rapid response time.

Smart hydrogels with high tunability of stiffness as a biomimetic cell carrier.

Human tissues are sophisticated ensembles of various distinct cell types encapsulated in the biomechanical cues of the extracellular matrix. It has been known matrix stiffness plays a pivot role in cellular events and tissue-scale biological processes. Thus, materials that can mimic mechanical environments of tissues in vitro and possess wide, physiologically relevant elasticity are highly desirable. Hydrogels provide a good cell platform to mimic native cellular environment. However, the limited stiffness tunability, and hinders the efforts to reproduce the biomechanical microenvironment of many in vivo progresses. These problems have been addressed by the recently emerged great quantity of exquisitely designed smart hydrogels. Smart hydrogels that respond sensitively to external stimuli are good choices due to the convenience in regulating their mechanical properties. In this review, we summarize the latest progress in the development of stimuli-responsive hydrogels as a cell carrier (platform for cell culture) which spans a wide range of stiffness. Different kinds of smart hydrogels corresponding to various stimuli, including pH, temperature, light, metal ions, and forces, are introduced and their stiffness modulation through physicochemical procedures are reported.