Dual-sensitive Hydrogel Research Articles

ROS/Thermo dual-sensitive hydrogel loaded with a nanoemulsion of patchouli essential oil for ulcerative colitis

Patchouli essential oil (PEO) is acknowledged as a potent contender for the management of ulcerative colitis (UC). However, the limited ability of PEO to be absorbed by the body and its low stability substantially limit its potential uses. Furthermore, UC lesions are mainly concentrated in the rectal and colonic mucosa, with excessive production of reactive oxygen species (ROS). Herein, a nanoemulsion of PEO (PEONE) was developed to enhance the stability and bioavailability of a drug. Subsequently, we developed a novel platform for the rectal administration of a ROS/thermo dual-sensitive Bletilla striata polysaccharide-based hydrogel (RTH) co-loaded with PEONE to efficiently treat UC. As expected, the sol–gel transition of PEONE@RTH, after its intrarectal administration, resulted in its extended presence in the colon and facilitated its attachment to the inflammation site. Moreover, PEONE@RTH alleviated dextran sulfate sodium-induced UC symptoms by suppressing inflammation and oxidative stress, repairing the damage to the intestinal epithelial barrier (claudin-1 and occludin), increasing short-chain fatty acid content and inhibiting the MAPK signalling pathway. Additionally, PEONE@RTH exhibits exceptional safety and biocompatibility. Thus, PEONE@RTH has the potential to provide a novel approach for treating UC and other intestinal disorders characterised by similar clinical conditions.

PH/Temperature Dual-Sensitive Hydrogel Based on Carboxymethyl Chitosan and a Pluronic for Combined Chemo-Photothermal Therapy

pH/Temperature Dual-Sensitive Hydrogel Based on Carboxymethyl Chitosan and a Pluronic for Combined Chemo-Photothermal Therapy

Facile fabrication of temperature/pH dual sensitive hydrogels based on cellulose and polysuccinimide through aqueous amino-succinimide reaction

A temperature/pH dual sensitive hydrogel with a semi-interpenetrating network (semi-IPN) structure was synthesized through an aqueous amino-succinimide reaction between water-soluble polysuccinimide and polyethyleneimine in the presence of thermosensitive cellulose derivatives. Single-factor experiments were carried out to optimize the preparation conditions of the semi-IPN hydrogel. The swelling behavior and cytotoxicity assay of the hydrogel were tested. Finally, taking 5- fluorouracil (5-Fu) as a model drug, the release performance of the 5-Fu-loaded hydrogel was investigated. The results indicated that the swelling ratio (SR) first decreased and then increased when the pH of the solutions ascended from 2 to 10. The SR decreased with the increase in temperature. In addition, the swelling behavior of the hydrogel was reversible and reproducible under different pH values and temperatures. The prepared hydrogels had good cytocompatibility. The release behavior of 5-Fu was most consistent with the Korsmeyer-Peppas model and followed the case II diffusion. The acidic environment was beneficial for the release of 5-Fu. The preparation process of the semi-IPN hydrogel is simple and the reaction can proceed quickly in water. The strategy introduced here has great potential for application in the preparation of drug carriers.

Preparation and properties of polyvinyl alcohol/chitosan-based hydrogel with dual pH/NH3 sensor for naked-eye monitoring of seafood freshness

To address the issue of food spoilage causing health and economic loss, we developed a pH/NH3 dual sensitive hydrogel based on polyvinyl alcohol/chitosan (PVA/CS) containing chitosan-phenol red (CP). The CP was synthesized via Mannich reaction and immobilized it in PVA/CS hydrogel through freezing/thawing method to prepare the final PVA/CS/CP hydrogel. The synthesis of CP was confirmed by 1H NMR, FT–IR, XRD, UV–vis, and XPS. The characteristics of hydrogel were evaluated by FT–IR, XRD, SEM, mechanical properties, thermal stability, leaching, and color stability tests. The PVA/CS/CP hydrogel showed distinctly different color at various pH and NH3 vapor levels (yellow to purple). The hydrogel exhibited obvious color changes (ΔE = 46.95) in response to shrimp spoilage, stored at 4 °C. It showed positive and strong correlation between the ΔE values of the indicator hydrogel and total volatile basic nitrogen (TVB-N) as (R2 = 0.9573) and with pH as (R2 = 0.8686), respectively. These results clearly show that the PVA/CS/CP hydrogel could be applied for naked-eye real-time monitoring of seafood freshness in intelligent packaging.

Exploring the potential of dual-sensitive hydrogels for personalized precision medicine applications

BackgroundMelanoma, the uncontrolled accumulation of malignant melanocytes, remains one of the most dangerous and deadly types of skin cancer. Current medical interventions, such as radiation and immunotherapy, are ineffective in treating malignant metastatic melanoma of the lung. Due to the complexity of cancer, abnormalities occur and lead to treatment failure. MethodsIn this study, a novel, dual-reaction hydrogel was composed of a thermo-sensitive type (fundamental) and a pH-sensitive type. In addition, the innovative hydrogel showed thermal reversibility and could liquefy at low temperatures and recover at room temperature. We used Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis (TGA), and rheometer to observe the hydrogel's mechanical properties. Significant findingsResults show the hydrogel had a small pore size, revealing positive interactions between molecular chains. The dual-reactive hydrogel exhibited the least cytotoxicity to B16F10 cells in vitro, indicating great biocompatibility and potential. The hydrogel in microparticles brings several advantages, including a high surface area-to-volume ratio and delivery within microscale structures. Microfluidic devices are promising for producing hydrogel particles because they enable high-precision flow control during microfabrication, resulting in precise size and shape. This study used a microfluidic device to produce hydrogel particles and encapsulate cells for future drug screening applications.

A novel adhesive dual-sensitive hydrogel for sustained release of exosomes derived from M2 macrophages promotes repair of bone defects

The repair of bone defects remains a huge clinical challenge. M2 macrophage-derived exosomes (M2-Exos) can act as immunomodulators to promote fracture healing; however, how to retain the sustained release of exosomes to the target area remains a challenge. Here, we report a composite hydrogel loaded with M2-Exos aiming to accelerate bone defect healing. It was verified that the F127/HA-NB hydrogel had a dense network structure, tissue adhesiveness, and dual sensitivity to temperature and light. F127/HA-NB loaded with M2-Exos (M2-Exos@F127/HA-NB) exhibited good biocompatibility and achieved sustained release of exosomes for up to two weeks. The study showed that both M0-Exos and M2-Exos@F127/HA-NB significantly promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells. The mechanism study implied that M2-Exos activates the Wnt/β-catenin signaling pathway to promote osteogenic differentiation of BMSCs. Finally, we evaluated the osteogenetic effects of M2-Exos@F127/HA-NB in a rat cranial defect model, and the results showed that M2-Exos@F127/HA-NB had superior bone regeneration-promoting effects. This study provides a new strategy for cell-free treatment of bone defects.

Chitin whiskers enhanced methacrylated hydroxybutyl chitosan hydrogels as anti-deformation scaffold for 3D cell culture

Hydrogel, as three-dimensional (3D) cell culture scaffold, is an effective strategy for tissue and organ regeneration due to their good biocompatibility, biodegradability and resemblance to body microenvironments in vivo. However, the inherent weak mechanical properties and strong shrinkage of hydrogels during cell culture hinder its application in clinical. In this study, a two-component thermo/photo dual-sensitive hydrogel (M/C) was prepared from methacrylated hydroxybutyl chitosan (MHBC) and chitin whisker (CHW) via physical and chemical cross-linking methods. M/C hydrogel showed a special internal structure with lamellar arrangement. The rheological properties of the hydrogels could be regulated with the change of M/C ratio. It is worth emphasizing that the mechanical properties, shrinkage resistance and cellular capacitances of the M/C hydrogel were improved with the addition of CHW. Moreover, the M/C hydrogel not only exhibited excellent degradability and antibacterial properties, but also significantly promoted the adhesion and proliferation of MC3T3-E1 cells in vitro. Therefore, the M/C hydrogel showed a wide application potential in tissue regeneration as a 3D cell culture scaffold.

Dual-sensitive drug-loaded hydrogel system for local inhibition of post-surgical glioma recurrence

Local treatment after resection to inhibit glioma recurrence is thought to able to meet the real medical needs. However, the only clinically approved local glioma treatment-wafer containing bis(2-chloroethyl) nitrosourea (BCNU) showed very limited effects. Herein, in order to inhibit tumor recurrence with prolonged and synergistic therapeutic effect of drugs after tumor resection, an in situ dual-sensitive hydrogel drug delivery system loaded with two synergistic chemo-drugs BCNU and temozolomide (TMZ) was developed. The thermosensitive hydrogel was loaded with reactive oxygen species (ROS)-sensitive poly (lactic-co-glycolic) acid nanoparticles (NPs) encapsulating both BCNU and TMZ and also free BCNU and TMZ. The in vitro synergistic effect of BCNU and TMZ and in vivo presence of ROS at the residual tumor site were confirmed. The prepared ROS-sensitive NPs and thermosensitive hydrogel, as well as the long-term release behavior of drugs and NPs, were fully characterized both in vitro and in vivo. After >90% glioblastoma resection, the dual-sensitive hydrogel drug delivery system was injected into the resection cavity. The median survival time of the experimental group reached 65days which was twice as long as the Resection only group, implying that this in situ drug delivery system effectively inhibited tumor recurrence. Overall, this study provides new ideas and strategies for the inhibition of postoperative glioma recurrence.

Synthesis of magnetic/pH dual responsive dextran hydrogels as stimuli-sensitive drug carriers

Hydrogels loaded with magnetic nanoparticles have been widely researched recently as biomaterials, due to their good biocompatibility and unique magnetic characteristics. In this study, water-soluble superparamagnetic iron oxide nanoparticles (Fe3O4) prepared by coprecipitation were physically doped into the dextran hydrogels which were formed via Schiff base reactions between ethylenediamine and oxidized dextran. The combination of magnetic nanoparticles and chemical cross-linked hydrogels leads to magnetic/pH dual-sensitive hydrogels which can be used as stimuli-responsive carrier. Magnetic properties, swelling, and rheology behaviors of the resulted magnetic hydrogels were strongly affected by the Fe3O4 nanoparticle content. Moreover, doxorubicin (DOX⋅HCl) was embedded into the magnetic hydrogels and pH/magnetic sensitive release profiles were identified. The release mechanism analysis indicated that the release behaviors of DOX⋅HCl were controlled by the diffusion, swelling, and erosion processes simultaneously. The prepared hydrogel/Fe3O4 composites with dual magnetic/pH stimuli-responsiveness hold the promise to be used in various applications such as drug release.

Thermosensitive hydrogel-functionalized gold nanorod/mesoporous MnO2 nanoparticles for tumor cell-triggered drug delivery

MnO2 owns distinct redox, imaging, and degradable properties corresponding to the tumor microenvironment. However, the onefold structure and non-modifiable property cause many obstacles to anticancer applications. In this report, we first prepared a typical core-shell gold nanorod (GNR)/manganese dioxide (MnO2) nanoparticles (GNR/MnO2 NPs). Interestingly, the MnO2 had a mesoporous channel and modifiable hydroxyl group (OH). Here, the unique ‘OH’ groups were modified and further grafted with poly(N-isopropylacrylamide-co-acrylic acid) (PNA). As a dual-sensitive hydrogel, it was selected as the thermal/pH-sensitive component in the hybrid nanoparticles (GNR/MnO2/PNA NPs). The anticancer drug doxorubicin hydrochloride (DOX) was selected and loaded into the hybrid nanoparticles (GNR/MnO2/PNA-DOX NPs). The GNR/MnO2/PNA NPs achieved satisfying drug-loading efficiency and glutathione (GSH)/pH/thermal-responsive drug-controlled release. As a side benefit, the GNR/MnO2/PNA NPs showed potential as excellent near-infrared (NIR)-excited nanoplatforms for photothermal therapy (PTT). Delightedly, the studies demonstrated that the GNR/MnO2/PNA-DOX NPs showed a noticeable killing effect on tumor cells, whether it is tumor cell-triggered drug release or photothermal effect. Besides, it not only could enhance mitochondrial damage but also could inhibit the migration and invasion of tumor cells. Quite the reverse, it had little negative impact on normal cells. The feature can prevent anticancer drugs and nanoparticles from killing normal cells. Consequently, GNR/MnO2/PNA NPs have potential applications in drug delivery and synergistic therapy due to these advantageous features.

A Dual-sensitive Hydrogel Based on Poly(Lactide-co-Glycolide)-Polyethylene Glycol-Poly(Lactide-co-Glycolide) Block Copolymers for 3D Printing.

The thermo-sensitive hydrogel formed by triblock copolymers of polyethylene glycols and aliphatic polyesters serves as a promising candidate for bioink due to its excellent biodegradability and biocompatibility. However, the thermo-crosslinking alone cannot achieve a robust hydrogel to support the 3D printed constructs without collapse. Herein, a photo-crosslinkable group was introduced into the triblock copolymers to achieve a dual-sensitive hydrogel. A triblock copolymer poly(lactide-co-glycolide)-polyethylene glycol-poly(lactide-co-glycolide) decorated with acrylate group in the chain end was prepared. The obtained aqueous solutions of the copolymers could transform into hydrogels with excellent shear thinning properties and rapid elastic recovery properties spontaneously on the increase of temperature. The resulted thermogels also allowed for photo-crosslinking by exposure to ultraviolet radiation, with storage modulus dramatically increased to stable the printed constructs. Through a two-step crosslinking strategy, complicated tissue-like constructs with high shape fidelity can be printed using the dual-sensitive inks. Moreover, the mechanical strength, swelling ratio, and printability of the hydrogels can be tuned by varying the substitution rate of the acrylate group without compromising the inks’ extrudability. We expect that the dual-sensitive hydrogels may be used as bioinks to print large constructs for applications in tissue engineering.

Budesonide-Loaded Pectin/Polyacrylamide Hydrogel for Sustained Delivery: Fabrication, Characterization and In Vitro Release Kinetics.

A single ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that causes inflammation of the colonic mucosa at the distal colon and rectum. The mainstay therapy involves anti-inflammatory immunosuppression based on the disease location and severity. The disadvantages of using systemic corticosteroids for UC treatment is the amplified risk of malignancies and infections. Therefore, topical treatments are safer as they have fewer systemic side effects due to less systemic exposure. In this context, pH sensitive and enzymatically triggered hydrogel of pectin (PC) and polyacrylamide (PAM) has been developed to facilitate colon-targeted delivery of budesonide (BUD) for the treatment of UC. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), swelling ratio, and drug release. FT-IR spectroscopy confirmed the grafting as well loading of BUD in hydrogel. XRD showed the amorphous nature of hydrogel and increment in crystallinity after drug loading. On the other hand, SEM showed that the hydrogels exhibited a highly porous morphology, which is suitable for drug loading and also demonstrated a pH-responsive swelling behaviour, with decreased swelling in acidic media. The in-vitro release of BUD from the hydrogel exhibited a sustained release behaviour with non-ficken diffusion mechanism. The model that fitted best for BUD released was the Higuchi kinetic model. It was concluded that enzyme/pH dual-sensitive hydrogels are an effective colon-targeted delivery system for UC.

Exosome loaded genipin crosslinked hydrogel facilitates full thickness cutaneous wound healing in rat animal model

Full thickness cutaneous wound therapy and regeneration remains a critical challenge in clinical therapeutics. Recent reports have suggested that mesenchymal stem cells exosomes therapy is a promising technology with great potential to efficiently promote tissue regeneration. Multifunctional hydrogel composed of both synthetic materials and natural materials is an effective carrier for exosomes loading. Herein, we constructed a biodegradable, dual-sensitive hydrogel encapsulated human umbilical cord-mesenchymal stem cells (hUCMSCs) derived exosomes to facilitate wound healing and skin regeneration process. The materials characterization, exosomes identification, and in vivo full-thickness cutaneous wound healing effect of the hydrogels were performed and evaluated. The in vivo results demonstrated the exosomes loaded hydrogel had significantly improved wound closure, re-epithelialization rates, collagen deposition in the wound sites. More skin appendages were observed in exosomes loaded hydrogel treated wound, indicating the potential to achieve complete skin regeneration. This study provides a new access for complete cutaneous wound regeneration via a genipin crosslinked dual-sensitive hydrogel loading hUCMSCs derived exosomes.

PEG-interpenetrated genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier compound formulation for topical drug administration

PEG-interpenetrated dual-sensitive hydrogels that load nano lipid carrier (NLC) were researched and developed for topical drug administration. Natural antioxidant α-lipoic acid (ALA) was selected as our model drug. The α-lipoic acid (ALA) nano lipid carrier was successfully prepared by hot melt emulsification and ultrasonic dispersion method, and the physicochemical properties of the nano lipid carrier were investigated, including morphology, particle distribution, polydispersity coefficient, zeta potential and encapsulation efficiency. Carboxymethyl chitosan and poloxamer 407 contributed to pH- and temperature-sensitive properties in the hydrogel, respectively. Natural non-toxic cross-linking agent genipin reacted with carboxymethyl chitosan to form the hydrogel. Poly ethylene glycol (PEG), a polymer compound with good water solubility and biocompatibility, interpenetrated the hydrogel and influenced the mechanical strength and drug release behaviour. FI-IR test verified the successful synthesis of the hydrogel. The rheological parameters indicated that the mechanical strength of the hydrogel was positively correlated with the amount of PEG, and the in vitro dissolution profiles demonstrated that the increasement of PEG could accelerate the drug release rate. The compatibility of the drug delivery system was verified with cells and mice model. Topical delivery of ALA in solution, NLC and NLC-gel was investigated in-vitro.

Preparation and Characterization of Thermal and pH Dual Sensitive Hydrogel Based on 1,3‐Dipole Cycloaddition Reaction

In this study, thermal and pH dual sensitive hydrogels were prepared via Cu‐free 1,3‐dipole cycloaddition between two copolymers which were modified by azide and maleimide functional groups, respectively. First, the thermally sensitive terpolymers were fabricated via conventional free‐radical polymerization of N‐isopropylacrylamide, hydroxyethyl methacrylate (HEMA), and N,N‐dimethylacrylamide (DMA). Then, polymeric dipolarophiles were synthesized via the esterification between the above terpolymers and N‐maleoyl alanine. Similarly, the pH‐sensitive terpolymers were also fabricated via conventional free‐radical polymerization of 4‐vinylpyridine, HEMA, and DMA, and then, polymeric dipoles were acquired via the decoration of the as‐prepared terpolymers with 2‐azidoacetic acid. Afterward, the smart hydrogels were fabricated via the aqueous 1,3‐dipole cycloaddition reaction between the as‐prepared polymeric dipolarophiles and dipoles without the use of catalysts. The results of swelling measurements confirm that the hydrogels possessed thermal and pH dual sensitivity. Moreover, the investigation of the behavior of oscillatory swelling shrinking indicates their sensitivity to temperature and pH was reversible and repeatable, which is of great significance for the repeated use of the prepared hydrogels. The proposed strategy demonstrates a great application prospects in the preparation of hydrogels as there were no catalysts and organic solvents employed. POLYM. ENG. SCI., 60:917–924, 2020. © 2020 Society of Plastics Engineers

Application of a mechanically responsive, inflammatory macrophage-targeted dual-sensitive hydrogel drug carrier for atherosclerosis

Atherosclerotic lesions create obvious vascular stenosis due to the presence of plaque, and a large number of inflammatory macrophages are enriched in the thrombus. In this study, we develop a composite hydrogel drug delivery system that is capable of both mechanically-sensitive drug release and of targeting inflammatory macrophages at the thrombus. The hydrogel is a high molecular weight hyaluronic acid (HA) modified with glycidyl methacrylate as a hydrogel precursor; a cross-linkable block copolymer (CBC) is used as the drug coating material and a microscopic cross-linking agent. The difference in drug release rate of the composite hydrogel (HACBC) in simulated blood vessels with 0 % and 75 % occlusion was as high as 49.3 %. Under long-term cycling conditions in stenotic vessels, dynamic shear rheometry revealed that the HACBC still maintained the hydrogel properties. However, the micelles were deformed and recombined to produce smaller sized micelles. An in vitro cell culture demonstrated precise targeting of the HACBC to inflammatory macrophages, and our rabbit experiments with simvastatin-coated HACBC confirmed the effective release of simvastatin in the plaque of the drug carrier. Moreover, we demonstrated the precise targeting of HACBC in vivo in apoE-/- mice by using HACBC coated with cy7. The mechanical stress-sensitive and CD44 receptor-targeted dual-response drug delivery system prepared by micellar composite hydrogel is the first application in the field of atherosclerosis, which provides a new method for diagnosing and treating atherosclerosis.

Injectable Hydrogels for Localized Cancer Therapy.

Traditional intravenous chemotherapy is relative to many systemic side effects, including myelosuppression, liver or kidney dysfunction, and neurotoxicity. As an alternative method, the injectable hydrogel can efficiently avoid these problems by releasing drugs topically at the tumor site. With advantages of localized drug toxicity in the tumor site, proper injectable hydrogel as the drug delivery system has become a research hotspot. Based on different types and stages of cancer, a variety of hydrogel drug delivery systems were developed, including thermosensitive, pH-sensitive, photosensitive, and dual-sensitive hydrogel. In this review, the latest developments of these hydrogels and related drug delivery systems were summarized. In summary, our increasing knowledge of injectable hydrogel for localized cancer therapy ensures us that it is a more durable and effective approach than traditional chemotherapy. Smart release system reacting to different stimuli at different time according to the micro-environment changes in the tumor site is a promising tendency for further studies.

Analysis of The Coupling Behavior of a Thin Layer of a Temperature-pH Dual Sensitive Hydrogel for an Inhomogeneous Large Deformation

Due to ionic migration and adsorption, an electrical double layer with a thickness scaled by the Debye length is formed at the hydrogel-solution interface. For a thin temperature-pH dual sensitive hydrogel whose chickness is comparable to the Debye length, its mechanical behavior may be affected by the electrical double layer. In this paper, by incorporating electromagnetic field theory into thermodynamic theory, we develop a coupled field theory for a temperature-pH dual sensitive hydrogel, and we take into account the electrical double layer. The proposed model can be used to analyze the influences of the size effect, ionic concentration, ambient temperature and solution pH value on the swelling of a thin layer of the temperature-pH sensitive hydrogel.

Dual-Sensitive Hydrogel Nanoparticles Based on Conjugated Thermoresponsive Copolymers and Protein Filaments for Triggerable Drug Delivery.

In this study, novel hydrogel nanoparticles with dual triggerable release properties based on fibrous structural proteins (keratin) and thermoresponsive copolymers (Pluronic) are introduced. Nanoparticles were used for curcumin delivery as effective and safe anticancer agents, the hydrophobicity of which has limited their clinical applications. A drug was loaded into hydrogel nanoparticles by a single-step nanoprecipitation method. The drug-loaded nanoparticles had an average diameter of 165 and 66 nm at 25 and 37 °C, respectively. It was shown that the drug loading efficiency could be enhanced through crosslinking of the disulfide bonds in keratin. Crosslinking provided a targeted release profile under reductive conditions using an in vivo agent, glutathione (GSH), or in the presence of trypsin. Cytocompatibility assay using HeLa and L929 fibroblast cells exhibited no adverse effect of nanoparticles on cell viability up to 1 mg/mL. Besides, the green fluorescence of curcumin confirmed the uptake of drug-loaded nanoparticles by cancer cells. The redox and temperature-sensitive nanoparticles are potentially useable for the efficient delivery of hydrophobic drugs to targeted regions having a triggerable release profile.

PH-Sensitive and Thermosensitive Hydrogels as Stem-Cell Carriers for Cardiac Therapy.

Stem-cell therapy has the potential to regenerate damaged heart tissue after a heart attack. Injectable hydrogels may be used as stem-cell carriers to improve cell retention in the heart tissue. However, current hydrogels are not ideal to serve as cell carriers because most of them block blood vessels after solidification. In addition, these hydrogels have a relatively slow gelation rate (typically >60 s), which does not allow them to quickly solidify upon injection, so as to efficiently hold cells in the heart tissue. As a result, the hydrogels and cells are squeezed out of the tissue, leading to low cell retention. To address these issues, we have developed hydrogels that can quickly solidify at the pH of an infarcted heart (6-7) at 37 °C but cannot solidify at the pH of blood (7.4) at 37 °C. These hydrogels are also clinically attractive because they can be injected through catheters commonly used for minimally invasive surgeries. The hydrogels were synthesized by free-radical polymerization of N-isopropylacrylamide, propylacrylic acid, hydroxyethyl methacrylate-co-oligo(trimethylene carbonate), and methacrylate poly(ethylene oxide) methoxy ester. Hydrogel solutions were injectable through 0.2-mm-diameter catheters at pH 8.0 at 37 °C, and they can quickly form solid gels under pH 6.5 at 37 °C. All of the hydrogels showed pH-dependent degradation and mechanical properties with less mass loss and greater complex shear modulus at pH 6.5 than at pH 7.4. When cardiosphere-derived cells (CDCs) were encapsulated in the hydrogels, the cells were able to survive during a 7-day culture period. The surviving cells were differentiated into cardiac cells, as evidenced by the expression of cardiac markers at both the gene and protein levels, such as cardiac troponin T, myosin heavy chain α, calcium channel CACNA1c, cardiac troponin I, and connexin 43. The gel integrity was found to largely affect CDC cardiac differentiation. These results suggest that the developed dual-sensitive hydrogels may be promising carriers for cardiac cell therapy.