Thermal Sensitive Hydrogel Research Articles

A thermo-sensitive hydrogel with prominent hemostatic effect prevents tumor recurrence via anti-anoikis-resistance

Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell–cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H2O2) catalyzed by intracellular GOx into oxygen (O2), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery.Graphical

Safe Induction of Acute Inflammation with Enhanced Antitumor Immunity by Hydrogel-Mediated Outer Membrane Vesicle Delivery.

Acute inflammation has the potential for the recruitment of immune cells, inhibiting tumor angiogenesis, metastasis, and drug resistance thereby overcoming the tumor immunosuppressive microenvironment caused by chronic inflammation. Here, an acute inflammation inducer using bacteria outer membrane vesicles (OMVs) loaded in thermal-sensitive hydrogel (named OMVs-gel) for localized and controlled release of OMVs in tumor sites is proposed. OMVs trigger neutrophil recruitment and amplify acute inflammation inside tumor tissues. The hydrogel ensures drastic inflammation is confined within the tumor, addressing biosafety concerns that the direct administration of free OMVs may cause fatal effects. This strategy eradicated solid tumors safely and rapidly. The study further elucidates one of the possible immune mechanisms of OMVs-gel therapy, which involves the assembly of antitumor neutrophils and elastase release for selective tumor killing. Additionally, tumor vascular destruction induced by OMVs-gel results in tumor darkening, allowing for combinational photothermal therapy. The findings suggest that the use of OMVs-gel can safely induce acute inflammation and enhance antitumor immunity, representing a promising strategy to promote acute inflammation application in tumor immunotherapy.

A stretchable, environmentally tolerant, and photoactive liquid metal/MXene hydrogel for high performance temperature monitoring, human motion detection and self-powered application

Conductive gels have received extensive attention in flexible electronics due to their diverse characteristics. The requirement for versatility and incompatibility of the conductive fillers with the hydrogel matrix remain a challenge for hydrogels. Herein, the cellulose nanofiber stabilized liquid metal droplets are utilized to initiate the polymerization and simultaneously serve as solid conductive fillers to construct the polyacrylamide/MXene/glycerol hydrogel with eligible stretchability (1000%) and high environmental adaptability (−25 to 80 °C) for multifunctional sensing. The hydrogel is utilized as a flexible electrode to construct the triboelectric nanogenerator for mechanical energy harvesting and conversion as well as self-powered sensing. Importantly, as a versatile sensor, it combines temperature sensing and deformation sensing with a wide range of stimulus responses and exceptional sensing performance. The flexible temperature and strain sensors are realized with superior thermosensitivity and strain sensitivity. In addition, the hydrogel exhibits favorable photothermal antibacterial ability. This work opens new avenues for the preparation of photothermal, conductive, stress and thermal sensitive hydrogels for multimodal sensors, sketching a promising future for them in flexible and wearable electronics.

Microgel-enhanced thermal-sensitive hydrogel electrolyte enables active heat management, controllable energy storage and mechanical flexibility of supercapacitors

Thermal runaway is a critical issue in energy storage process, leading to damage even failure of energy storage devices. Herein, active heat management, controllable energy storage and mechanical flexibility of supercapacitors are achieved by utilizing microgel-enhanced thermal-sensitive hydrogels as electrolytes. Because of the improved thermal sensitivity of microgel-enhanced hydrogel electrolyte, heat can be efficiently consumed by volume phase transition process, and meanwhile the energy storage process is also weakened by slowing down the ion transport. Reversibly controlled energy storage is also demonstrated in such supercapacitors. By varying temperature below and above volume phase transition temperature (VPTT) of hydrogel electrolytes, the specific capacitance is switched between 124 mF cm−2 and 9 mF cm−2. Moreover, the hydrogel electrolytes also endow such supercapacitors mechanical flexibility and stable charge–discharge under a bending angle from 0 to 180° has been demonstrated. Overall, this work has provided a new clue to construct intelligent hydrogel devices by elegant structure design.

Biodegradable photothermal thermosensitive hydrogels treat osteosarcoma by reprogramming macrophages.

Osteosarcoma is one of the most common malignant tumors in children and tends to occur around the knee. Problems such as recurrence and metastasis are the outcomes of traditional treatment methods. One of the reasons for these issues is the infiltration of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Photothermal immunotherapy has emerged as one of the most potent approaches for cancer treatment. In this study, we designed a biodegradable, injectable, and photothermal hydrogel that functions to reprogram TAMs into classically activated macrophages (M1) based on hydroxypropyl chitin (HPCH), tannic acid and ferric ions (HTA). We found that HTA had better photothermal efficiency than a pure hydrogel; its photothermal repeatability is good and it can be NIR (808 nm) irradiated as needed. In addition, the precooled hydrogel solution can be injected into the tumor and it can rapidly gel in situ. In vitro, HTA with NIR irradiation (HTA + NIR) induced the apoptosis of K7M2 cancer cells. In vivo, the local administration of HTA + NIR exerted photothermal killing of primary tumors and reprogramming of TAMs into M1-type macrophages in the TME. Therefore, the injectable photothermally active antitumor hydrogel has great potential for modulating the TME to treat bone tumors.

Embedded Cooling of High-Heat-Flux Hotspots Using Self-Adaptive Microchannel/Pin-Fin Hybrid Heat Sink

The chips present unsteady and highly concentrated heat fluxes and the available volume for cooling solution is significantly constrained with the trend of miniaturization and integration. Traditional liquid cooling techniques fail to regulate the coolant distribution according to the changing thermal environment and remove the unevenly distributed thermal loads effectively. In this article, embedded cooling with self-adaptive microchannel/pin-fin hybrid heat sink is proposed. Hybrid channels with thermal-sensitive hydrogels at the outlet are designed and integrated into the substrate. A numerical model is established and an iteration procedure is designed to investigate the flow regulation behavior. The hydrogel downstream of the hotspot undergoes volume reduction and the local coolant flow rate is enlarged, illustrating the autonomous flow regulation effect. Various nonuniform heat load distributions are considered. Taking advantage of the current self-adaptive cooling solution, heat flux of up to 500 W/cm2 can be dissipated and the peak temperature is reduced by 12.2 K with a pressure drop of 34.0 kPa. The embedded self-adaptive cooling provides both effective and intelligent thermal management for densely integrated electronics.

Impacting different structures of injectable pluronic-conjugated alginate (chitosan) hydrogels on their physicochemical characteristics and morphological fibroblast behavior

Chitosan and alginate have inherent properties that have a tremendous impact on the design of in situ thermal sensitive hydrogels due to their ability to fill complex three-dimensional damaged tissue gaps, which can be applied in the tissue regeneration or drug delivery systems. In this study, pluronic F127-conjugated alginate (Alg-F127) and pluronic F127-conjugated chitosan (CS-F127) copolymers were investigated for their physicochemical characteristics and morphological fibroblast behavior. The structures of the amphiphilic copolymers were characterized by 1H-NMR. The aqueous copolymer solution could reversibly change its state from sol to gel via hydrophobic interactions at body temperature (35°–37 °C). At the same concentration of two grafted copolymers, the alginate-based hydrogel performed higher resistance to degrade in both PBS buffer and DMEM. Regarding their specific charge, CS-F127 showed higher protein absorption as compared to the Alg-F127 copolymer. The typical characteristic could induce the different morphological cell behaviors on the hydrogel platforms. Interestingly, as an inherent characteristic of fibroblasts, the cells were elongated and migrated directionally on the Alg-F127 scaffold, though both had excellent cytocompatibility. The improved understanding of the influence of polysaccharide structure on cell behavior has a significant impact on the design of biomedical devices and specific tissue regeneration.

Self-adaptive cooling of chips with unevenly distributed high heat fluxes

• A self-adaptive chip cooling method for high heat fluxes is proposed. • Unevenly distributed high heat fluxes of up to 460 W/cm 2 are effectively removed. • The maximum surface temperature drop amounts to 22.6 K with reduced flow rates. • Coolant flow adapts to local heat fluxes and movable hotspots are cooled effectively. The heat load scenario of a real chip is unsteady and spatially variable and gives rise to regions of concentrated high power. Conventional liquid cooling techniques are always inadequate to tailor the flow distribution to the changing thermal environment and cool the resulting high-heat-flux regions effectively. In this work, the self-adaptive cooling for unevenly distributed high heat fluxes is proposed. It contains a matrix of microfluidic units with integrated thermal-sensitive hydrogel valves. The units are independently controlled and deliver the coolant to where it is needed. A numerical model is developed to investigate the flow and temperature distribution of the cooling unit. By introducing the self-adaptive mechanism, the near-wall flow is enhanced remarkably. Nonuniform heat fluxes of up to 460 W/cm 2 are effectively dissipated by means of the developed self-adaptive cooling method. The maximum surface temperature drop amounts to 22.6 K, meanwhile the total flow rate can be reduced by nearly an order of magnitude. The microfluidic unit array adapts to local heat fluxes by reconfiguring its internal flow-channel structure automatically and thus movable hotspots are elaborately cooled. The self-adaptive cooling scheme offers both effective and smart thermal management for modern electronic devices.

Thermal-Sensitive Hydrogel Microneedle for Controlled Transdermal Drug Delivery

Thermal-Sensitive Hydrogel Microneedle for Controlled Transdermal Drug Delivery

Multifunctional injectable pluronic-cystamine-alginate-based hydrogel as a novel cellular delivery system towards tissue regeneration

This paper presents a new thermal sensitive hydrogel system based on cystamine-functionalised sodium alginate-g-pluronic F127 (ACP). The introduction of cystamine to the alginate backbone not only creates a covalent bond with pluronic F127 but also provides intrinsic anti-bacterial activity for the resultant hydrogel. The amount of water uptake inside the hydrogel remained ~200% for 6 days and the degradation was completed in 12 days in physiological media. The ACP copolymer solution could form a hydrogel at body temperature (~37 °C) and could return to the solution phase if the temperature decreased below 25o °C. Fibroblast encapsulated in situ in the ACP hydrogel maintained their viability (≥90% based on the live/dead assay) for 7 days, demonstrating the good biocompatibility of the ACP hydrogel for long-term cell cultivation. In addition, three-dimensional (3D) culture showed that fibroblast attached to the hydrogels and successfully mimicked the porous structure of the ACP hydrogel after 5 days of culture. Fibroblast cells could migrate from the cell-ACP clusters and form a confluent cell layer on the surface of the culture dish. Altogether, the obtained results indicate that the thermal-responsive ACP hydrogel synthesised in this study may serve as a cellular delivery platform for diverse tissue engineering applications.

NIR responsive tumor vaccine in situ for photothermal ablation and chemotherapy to trigger robust antitumor immune responses

BackgroundTherapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel.ResultsHA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen.ConclusionTaken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.

Cellulose nanocrystals reinforced highly stretchable thermal-sensitive hydrogel with ultra-high drug loading

Hydrogels often have poor mechanical properties which limit their application in load-bearing tissues such as muscle and cartilage. In this work, a near-infrared light-triggered stretchable thermal-sensitive hydrogel with ultra-high drug loading was developed by a combination of natural polymeric nanocrystals, a network of synthetic thermo-responsive polymer, and magnetic Fe3O4 nanoparticles. The hydrogels comprise cellulose nanocrystals (CNCs) decorated with Fe3O4 nanoparticles (Fe3O4/CNCs) dispersed homogeneously in poly(N-isopropylacrylamide) (PNIPAm) networks. The composite hydrogels exhibit an extensibility of 2200%. Drug loading of vancomycin (VCM) reached a high value of 10.18 g g−1 due to the dispersion of Fe3O4/CNCs and the interactions between the CNCs and the PNIPAm network. Importantly, the hydrogels demonstrated a thermo-response triggered by NIR, with the temperature increasing from 26 to 41 °C within 60 s. The hydrogels have high biocompatibility evidenced by cell proliferation tests, illustrating that these hydrogels are promising as dressings for wound closure, and wound healing.

Crystallization enhanced thermal-sensitive hydrogels of PCL-PEG-PCL triblock copolymer for 3D printing

Temperature-sensitive hydrogels with mild gel-forming process, good biocompatibility and biodegradability have been widely studied as bioinks and biomaterial inks for 3D bioprinting. However, the hydrogels synthesized via copolymerization of aliphatic polyesters and polyethylene glycols have low mechanical strength and cannot meet the needs of 3D printing. In this paper, we propose a strategy of enhancing the strength of hydrogels by introducing crystallization between blocks to meet the requirements of 3D bioprinting inks. A series of polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock polymers were prepared by ring-opening polymerization, of which the strong crystallinity of polycaprolactone blocks improved the printability and enhanced the mechanical properties of the ink. It was found that the resulted hydrogels were temperature-responsive, and the PCL blocks could form a crystalline phase in the state of the hydrogel, thereby significantly increasing the modulus of the hydrogel. Moreover, the mechanical strength of the hydrogel could be adjusted by changing the composition ratio of each block of the copolymer. The 3D printing results showed that the PCL-PEG-PCL hydrogel with crystallinity can not only be extruded and printed via temperature adjustment, but also the three-dimensional structure can be effectively maintained after 3D printing. The gels demonstrated good cell compatibility, and the cell survival rate was maintained at a high level.

Formulation, characterization and in vitro anti-leishmanial evaluation of amphotericin B loaded solid lipid nanoparticles coated with vitamin B12-stearic acid conjugate.

Despite the advancement of new anti-leishmanials, amphotericin B (AmB) prevails as one of the most potent agent in the treatment of visceral leishmaniasis (VL), a neglected tropical disease affecting mostly poverty ridden and underdeveloped regions of the globe. Nonetheless, many patients display intolerance to parenteral AmB, notably at higher dosages. Also, conventional AmB presents an apparently poor absorption. Therefore, to improve AmB bioavailability and overcome multiple barriers for oral delivery of AmB, we fabricated a promising vitamin B12-stearic acid (VBS) conjugate coated solid lipid nanoparticles (SLNs) encapsulated with AmB (VBS-AmB-SLNs) by a combination of double emulsion solvent evaporation and thermal sensitive hydrogel techniques. VBS-AmB-SLNs showed a particle size of 306.66±3.35nm with polydispersity index of 0.335±0.08 while the encapsulation efficiency and drug loading was observed to be 97.99±1.6% and 38.5±5.6% respectively. In vitro drug release showed a biphasic release pattern and chemical stability of AmB was ensured against simulated gastrointestinal fluids. Cellular uptake studies confirmed complete internalization of the formulation. Anti-leishmanial evaluation against intramacrophage amastigotes showed an enhanced efficacy of 94% which was significantly (P<0.01) higher than conventional AmB without showing any toxic effects on J774A.1 cells. VBS-AmB-SLNs could serve as a potential therapeutic strategy against VL.

Intranasal delivery system of bacterial antigen using thermosensitive hydrogels based on a Pluronic-Gantrez conjugate.

Thermosensitive hydrogels have been studied as feasible needle-avoidance alternative to vaccine delivery. In this work, we report the development of a new thermal-sensitive hydrogel for intranasal vaccine delivery. This delivery system was formulated with a combination of the polymer Gantrez® AN119 and the surfactant Pluronic® F127 (PF127), with a high biocompatibility, biodegradability and immunoadjuvant properties. Shigella flexneri outer membrane vesicles were used as the antigen model. A stable and easy-to-produce thermosensitive hydrogel which allowed the incorporation of the OMV-antigenic complex was successfully synthetized. A rapid gel formation was achieved at body temperature, which prolonged the OMV-antigens residence time in the nasal cavity of BALB/c mice when compared to intranasal delivery of free-OMVs. In addition, the bacterial antigens showed a fast release profile from the hydrogel in vitro, with a peak at 30min of incubation at 37°C. Hydrogels appeared to be non-cytotoxic in the human epithelial HeLa cell line and nose epithelium as well, as indicated by the absence of histopathological features. Immunohistochemical studies revealed that after intranasal administration the OMVs reached the nasal associated lymphoid tissue. These results support the use of here described thermosensitive hydrogels as a potential platform for intranasal vaccination.

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

Extravascular gelation shrinkage-derived internal stress enables tumor starvation therapy with suppressed metastasis and recurrence

Despite the efficacy of current starvation therapies, they are often associated with some intrinsic drawbacks such as poor persistence, facile tumor metastasis and recurrence. Herein, we establish an extravascular gelation shrinkage-derived internal stress strategy for squeezing and narrowing blood vessels, occluding blood & nutrition supply, reducing vascular density, inducing hypoxia and apoptosis and eventually realizing starvation therapy of malignancies. To this end, a biocompatible composite hydrogel consisting of gold nanorods (GNRs) and thermal-sensitive hydrogel mixture was engineered, wherein GRNs can strengthen the structural property of hydrogel mixture and enable robust gelation shrinkage-induced internal stresses. Systematic experiments demonstrate that this starvation therapy can suppress the growths of PANC-1 pancreatic cancer and 4T1 breast cancer. More significantly, this starvation strategy can suppress tumor metastasis and tumor recurrence via reducing vascular density and blood supply and occluding tumor migration passages, which thus provides a promising avenue to comprehensive cancer therapy.

Preparation of Immunotherapy Liposomal-Loaded Thermal-Responsive Hydrogel Carrier in the Local Treatment of Breast Cancer.

To reduce the side effects of immune drugs and the sustainable release of immune drugs on local parts, we have designed an injectable thermal-sensitive hydrogel containing an imiquimod-loaded liposome system. In the extracellular environment of tumor tissues (pH 6.4), 50% of the drug was released from the carrier, which could be a result of the morphological changes of the liposomal microstructure in the acidic environment. According to the results in animals, the drug-containing liposomes combined with hydrogel can be effectively applied in breast cancer therapy to delay the growth of tumors as well as to dramatically reduce the death rate of mice.

Facile and green preparation of thermal and ph sensitive hydrogel microspheres based on spray drying and the diels–alder reaction

Thermal and pH dual‐sensitive hydrogel microspheres were fabricated using spray drying. During the spray drying, chemical crosslinks were formed in situ via the Diels–Alder reaction without the involvement of any catalysts or organic solvents. The structures and morphologies of the products were characterized by Fourier Transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), Raman spectroscopy, scanning electron microscopy (SEM), X‐ray diffraction (XRD), and thermogravimetric analysis (TGA). A general weighing method was applied to study the swelling behavior of the microspheres at different temperatures and pHs. Using urea as a model molecule, the ability of the microspheres to control the release of urea was explored by spectrophotometry and calculated from the calibration curve obtained from the reaction of urea and diaminobenzaldehyde. The as‐prepared microspheres show a reversible and reproducible volume change with varying pH or temperature, and their swelling ratios increase with increasing temperature or pH. Furthermore, the urea release rates can be tuned by changing the pH or the temperature. Since spray drying can easily produce microspheres on a large scale, the strategy demonstrated here has the potential for applications in the green preparation of hydrogel microspheres. POLYM. ENG. SCI., 59:1999–2007, 2019. © 2019 Society of Plastics Engineers

A dual synergistic of curcumin and gelatin on thermal-responsive hydrogel based on Chitosan-P123 in wound healing application

This study aimed to fabricate the potential therapeutic scaffold to efficiently and safely fastening skin wound healing. A biocompatible grafting polymer-based thermal sensitive hybrid hydrogel (Chitosan-P123, CP) containing gelatin and curcumin was designed to be suitable stiffness for tissue regeneration. A detailed in the rheological study found that the encapsulated agents induced the change in the stiffness of the hydrogel from the hard to the soft. Especial, the thermally induced phase transition of CP hydrogel was governed by the participant of gelatin rather than curcumin. For example, at 25 wt% gelatin, CP hydrogel exhibited a unique gel–sol-gel transition following the function of temperature. Moreover, in vitro investigation revealed that the hybrid hydrogel provides the capacity of especially induced curcumin release with a sustainable rate as well as the excellent biocompatibility scaffold. Altogether with in vivo study, the hybrid hydrogel highlighted the advance of the dual synergistic of curcumin and gelatin in development of smart scaffold system, which promoted the efficacy in the regeneration of the structure and the barrier's function of damaged skin such as wound or skin cancer.