Clinical translation of adipose-derived stem cell (ADSC)-derived extracellular vesicles (EVs) for cutaneous regeneration is challenged by variable secretion levels, heterogeneous molecular cargo, and inconsistent therapeutic potency. Here, we developed a mechanically tunable and biomolecularly instructive photocurable hybrid hydrogel (GelMA/HAMA/PEGDA) that serves both as a 3D culture microenvironment for ADSCs and as an EV-delivery scaffold. Systematic screening of PEGDA-controlled crosslinking identified GH11P (97% [15% GelMA : 1% HAMA = 1 : 1 (v/v)] + 3% PEGDA) as a formulation with balanced stiffness, controlled degradation, and cytocompatibility, supporting EV production under 3D culture. Multi-omics profiling suggested that EVs produced in this 3D matrix (3D-hcEVs) exhibit regenerative-associated signatures, including ECM-integrin interactions, focal adhesion-related pathways, PI3K-AKT signaling, and a keratin-enriched proteomic signature compared with dish-cultured EVs (dcEVs). Additional in vitro validation showed that 3D-hcEVs enhanced HaCaT migration and more strongly increased p-AKT/AKT than dcEVs at 30 and 60 min. An NTA-based in vitro release assay further demonstrated partial, sustained EV release from GH11P over 7 days. In a full-thickness dorsal wound model, GH11P scaffolds loaded with 3D-hcEVs accelerated wound closure compared with dcEV-loaded scaffolds and hydrogel-only controls. Histological analyses further indicated improved tissue regeneration features, including enhanced re-epithelialization, epidermal stratification, collagen organization, increased CD31+ neovascularization, and reduced CD68+ macrophage infiltration. Collectively, these results support the feasibility of a tunable hydrogel platform that integrates mechanical and biomolecular microenvironmental cues to modulate EV-associated molecular signatures and evaluate EV delivery for cutaneous wound repair.

A functionalized photocrosslinked organic-inorganic hybrid hydrogel for strawberry preservation and multimodal sensing.

Wound infections pose a substantial clinical challenge and an escalating healthcare burden, further complicated by the rapid increase in multidrug-resistant bacteria. Antimicrobial peptides (AMPs) offer an alternative to conventional antibiotics, but their rapid degradation, hemolytic activity, and potential cytotoxicity complicate systemic delivery and can have negative impact on wound healing. Here we show a bacterial nanocellulose hyaluronan (BC-HA) hybrid hydrogel wound dressing functionalized with mesoporous silica nanoparticles (MSNs) for localized, enzyme responsive delivery of a sequence optimized antimicrobial peptide (SOAP) for treatment of infected wounds. The dressings provide moisture retention and excellent skin conformability while enabling infection-triggered AMP release by bacterial and host proteases. In vitro, SOAP-loaded dressings showed potent activity against clinical wound pathogens while remaining compatible with human primary dermal fibroblasts and keratinocytes. In a contaminated porcine wound model, the dressings significantly reduced bacterial load while accelerating wound re-epithelialization and epithelial maturation compared to the controls. By integrating a dual-function hydrogel that promotes healing and provides on-demand antimicrobial activity, critical limitations in the use of AMPs in wound care can be addressed, providing new possibilities to treat infected wounds.

Neurological disorders severely impair the daily life of patients, necessitating precise assessments of neural conduction pathway damage to guide effective diagnosis and treatment. However, current clinical neurodiagnostic equipment is expensive, bulky, and restricted to hospital settings. Furthermore, the rigid nature and low adhesion of conventional electrodes lead to the acquisition of low-quality neurophysiological signals. Here, we develop a soft hybrid electronic system assembled with printed responsive hydrogel electrodes. By synthesizing thermoresponsive hydrogel microsphere inks, we achieve rapid direct-printed patterning of interface layers. Based on a thermally triggered hydration-dehydration strategy of hydrogel microspheres, the hydrogel electrodes demonstrate customizable adhesion, enabling intimate integration with skin for high-fidelity signal acquisition and gentle detachment after monitoring. Through hydrogel interface modification, on-skin electrodes also show excellent charge injection capability for stimulation and improved signal-to-noise ratio (SNR). The integration of hydrogel patches with the hybrid electronic system enables high-frequency and high-fidelity acquisition of subtle neural conduction signals. We further apply this system to assess injuries to the median and ulnar nerves in clinical cases, realizing accurate diagnosis of neural impairment while ensuring customized adhesion regulation. This user-friendly system holds great promise as a low-cost and portable diagnostic platform for telemedicine, home-based care, and clinical settings.

ATP-responsive injectable DNA hybrid hydrogels for regulating the "on-demand release" of fibroblast growth factor 21 cytokines to facilitate muscle regeneration.

Quasi solid-state thermocells (QTECs) based on the thermogalvanic effect offer a promising route for directly converting abundant low-grade heat into electricity. Introducing a single solvent into hydrogel electrolytes, a common strategy to enhance thermopower, often yields a marginal solvation entropy difference between redox ions and provides limited gains in ion transport. To break this longstanding trade-off, we present a simple yet highly effective co-solvent strategy that employs trimethyl phosphate and ethylene glycol to construct hybrid hydrogel electrolytes. This approach synergistically enlarges solvation entropy differences of redox ions, amplifies the concentration gradient across the thermocell, and enhances redox ion transport through the hydrogel network. The resulting hydrogel electrolyte achieves superior thermoelectrochemical performance and demonstrates efficient harvesting of low-grade heat even at sub-zero temperatures. Advanced characterization techniques, integrated with molecular simulations, elucidate that the enhanced thermoelectrochemical performance originates from co-solvent engineered asymmetric solvation structures. This work demonstrates targeted, additive-free modulation of the solvation environment in thermogalvanic hydrogels as a practical strategy to significantly enhance thermoelectrochemical performance.

This review explores gels that assemble from low-molecular-weight gelator (LMWG) building blocks for use in cell culture, with a focus on fibroblasts and stem cells. These LMWG hydrogels have unique potential for controlling and directing cell growth. We provide an overview of gel tunability and how careful molecular design can direct biological outcomes. The LMWG hydrogel approach to cell growth is based on reversible assembly, potentially enabling cells to be encapsulated and subsequently released. It is possible to easily formulate multiple active ingredients into LMWG hydrogels by co-assembly - a powerful strategy to create multi-functional hybrid hydrogels. Rheological properties can be tuned over orders of magnitude, with stiffness helping control properties like cell invasion or stem cell differentiation. Furthermore, gel dynamics at both molecular and network levels can control factors such as cell adhesion. By developing strategies to shape and pattern these gels, it is possible to create structured assemblies of cells or direct the growth of multi-functional biological tissues. The dynamic characteristics of these gels enables them to evolve, potentially facilitating 4D tissue engineering or the creation of materials that are both bio-instructive and bio-responsive. LMWG hydrogels have been applied both in vitro and in vivo and some are in commercial use. This critical review provides an overview of progress to date, emphasising the unique advantages of the LMWG hydrogel approach, and highlighting concepts that might unlock untapped potential, hence transforming next-generation regenerative medicine.

Efficient photocatalytic hydrogen evolution in hybrid hydrogels containing photocatalysts remains a challenge due to the rapid loss of water and poor light harvesting. To overcome this drawback, an electrospun poly(vinylidene fluoride) (PVDF) fibrous layer with an unconnected porous structure is coated on hybrid hydrogels to improve the photocatalytic hydrogen evolution. The hybrid hydrogels are prepared by the thermally initiated polymerization of the monomers poly(ethylene glycol) methyl ether methacrylate (OEGM300) and di(ethylene glycol) methyl ether methacrylate (MEO2MA) with g-C3N4/Pt nanosheets. After that, an electrospun PVDF fibrous layer with a porous structure is constructed on the hydrogel surface by first electrospinning a solution containing PVDF and poly(ethylene oxide) (PEO) and then removing PEO. To optimize photocatalytic performance, the weight fraction of PEO is increased from 0.2 to 0.5 and finally to 0.8. Simultaneously, the porous structure in the nanofibers switches from an unconnected to a fully connected state. Due to the existence of unconnected pores in the PVDF fibrous layer, the evaporated water molecules from hydrogels can be captured and returned to the liquid state. They act as tiny mirrors to reflect the light scattered from the hydrogel surface. Thus, light harvesting is enhanced. The hydrogen evolution rate prominently increases to 3491 μmol h-1 g-1, which is almost double that without a fibrous layer covering. In addition, evaporation also slows down due to cycles of evaporation and condensation of water molecules. The weight loss of hybrid hydrogels coated with an electrospun PVDF0.5 fibrous layer with an unconnected porous structure is only 43.5% to that without any PVDF fibrous layer. It significantly prolongs the lifetime. For this reason, the present hybrid hydrogel system is well suited for photocatalytic hydrogen evolution in deserts and prairies, which are rich in solar energy but lack water.

Magnetothermally responsive fibrin hydrogel for localized neuromodulation.

Advances in hybrid hydrogels for diabetic wound healing.

Supramolecular peptide hydrogels offer attractive bioactivity and dynamic mechanical behavior for three-dimensional cell culture and tissue engineering. However, their broader use is often limited by slow gelation and insufficient mechanical stability. Here, we introduce a molecular design strategy in which a tryptophan zipper pendant multiarm poly (ethylene glycol) (Trpzip-PEG) conjugate is incorporated into Trpzip nanofibrillar hydrogels to facilitate hierarchical tuning of materials properties. Trpzip peptides self-assemble into entangled nanofiber networks, while the addition of Trpzip-PEG conjugate induces reorganization of these assemblies. Electron microscopy and neutron scattering reveal more densely bundled fibers with increased microporosity and a fractal network architecture, suggesting that the conjugate acts as a supramolecular binder or "staple" coordinating nano- and micro-scale organization. These structural changes markedly accelerate gelation and increase stiffness, yield behavior, and thixotropic recovery. Importantly, the Trpzip/Trpzip-PEG supramolecular hybrid hydrogels remain cytocompatible, supporting adipose-derived stem cell adhesion, viability, and proliferation over time. Together, these findings demonstrate that Trpzip/Trpzip-PEG hybrid hydrogels offer a versatile platform for engineering mechanically robust yet bioactive soft materials for 3D cell culture, biofabrication, and regenerative medicine applications.

Diabetic foot ulcers are challenging to manage and require intensive treatment as they heal slowly and greatly affect quality of life due to reduced mobility, infection and sepsis. The aim of current study was to develop novel hybrid hydrogels of silk fibroin containing 0.5%, 1.0% and 1.5% of Catharanthus roseus extract. Prepared hydrogels were characterized and GC-MS analysis of C. roseus extract was done to assess the component composition. Swiss albino mice were injected with alloxan to develop diabetic models and foot ulcer was induced. Hydrogels were administered every other day and wound healing potential was observed. GC-MS analysis revealed various antidiabetic and antibacterial constituents in C. roseus, while FT-IR results of hydrogels indicated intramolecular interactions between CMC, sodium alginate, fibroin and C. roseus extracts. The hydrogels showed more than 100% swelling ratio along with uniform surface morphology depicted by SEM analysis. Wound healing was notably faster (more than 80%) in mice treated with formulated hydrogels as compared to negative control group which showed just a 42% reduction in ulcer size by day 14. Similarly, in the treatment groups, IL-10 and TIMPs were significantly increased, whereas pro-inflammatory cytokines and matrix metalloproteinases were decreased. Histological analysis showed clear distinctions between diabetic and non-diabetic pancreas supported by HbA1c and C-peptide levels. Hydrogels treated groups exhibited enhanced angiogenesis, collagen fiber restoration and granulation tissue formation, indicating wound healing. In conclusion, this research shows that 1.5% C. roseus extract infused with silk Fibroin hydrogel has proved an efficient healing and rapid wound contraction of the diabetic foot ulcer in mice on day 14.

Characterization and development of a gelatin/elastin methacrylamide-based bioink for creating a 3D bioprinted human skin model.

Solar-driven interfacial evaporation presents a promising, sustainable route for desalination and wastewater treatment. However, simultaneously removing heavy metal contaminants from water and soil during the evaporation process remains a significant challenge. Here, we designed a hybrid hydrogel that integrates solar evaporation with the removal of heavy metals. The hydrogel was synthesized by embedding carbon nanotubes (CNTs) into a sodium alginate/polyacrylamide (SA/PAM) polymer network, enabling the efficient removal of heavy metal ions from wastewater and soil. The key to its function lies in the abundant -COO- groups from SA, which offer specific chelation sites for heavy metal ions, enabling effective immobilization through ion exchange and coordination. Under 1 kW m-2 irradiation, the hydrogel achieved an evaporation rate of 1.96 kg m-2 h-1 while simultaneously adsorbing heavy metal ions, with enhanced capacities of 112.40 mg g-1 for Cd2+ and 117.80 mg g-1 for Cu2+. More importantly, the hydrogel demonstrated effective remediation of contaminated soil, reducing the Cu2+ concentration to below the agricultural soil risk-screening threshold. This work demonstrates an integrated strategy for simultaneous water purification and soil remediation achieved by combining photothermal conversion and selective adsorption within a single material platform.

Freshwater scarcity driven by climate variability, population growth, and uneven infrastructure is accelerating the need for decentralized water capturing technologies (WCT). Hydrogel-based materials have emerged as versatile platforms for three complementary pathways: solar steam generation (SSG) for desalination, sorption-driven atmospheric water harvesting (AWH), and surface-engineered fog capture (FC). Although numerous hydrogel formulations have been reported, performance metrics vary widely due to inconsistent testing conditions and limited long-term validation, complicating meaningful comparison and practical assessment. This review adopts a unified, mechanism-oriented framework to analyze hydrogel-enabled water capture. We examine how water-state regulation, hierarchical transport architecture, and surface interactions collectively govern heat and mass transfer across SSG, AWH, and FC systems. Rather than focusing only on laboratory performance, we extract frequent functional strategies, identify design trade-offs between sorption strength and regeneration, thermal localization and salt stability, and adhesion versus drainage control, and clarify ongoing discussions regarding evaporation thermodynamics. In addition, we discuss manufacturing scalability, cost-reporting limitations, and system-level integration required for real-world implementation. Finally, we synthesize durability mechanisms, including salt crystallization, microbial growth, UV exposure, mechanical fatigue, and additive migration, and propose standardized laboratory and field reporting parameters to improve reproducibility. By linking polymer design principles to application-specific constraints, this review provides a comparative and application-oriented roadmap for advancing hydrogel-based WCT. • A unified, mechanism-oriented framework is used to analyze hydrogel-enabled water capture technologies. • Hybrid and biomass-based hydrogels are included. • Design trade-offs for production and application-specific functionality are broadly evaluated. • A comparative and application-oriented roadmap for advancing hydrogel-based WCT is provided.

Microenvironment responsive copper-polyphenol nanozyme hybrid hydrogel with NO/O2 release for healing diabetic infected wounds via immunomodulation and angiogenesis

In situ forming gelatin/gellan gum hybrid hydrogels containing graphene quantum dots for imaging and effective drug delivery of 5-fluorouracil in local therapy of breast cancer.

Chitosan-gelatin hybrid hydrogel incorporating strontium-doped ceria nanoparticles for enhanced wound healing and mitochondrial function recovery.

Liquid metal (LM)-derived electronic skin (e-skin) exhibits significant potential in the domains of human-machine interfaces, health monitoring and energy management. Herein, we introduce a cost-effective paradigm of LMs-derived e-skin featuring anti-freezing capability, efficient thermal management, and motion detection. The inexpensive and eco-friendly porous pomelo pith (PP) is employed as the substrate for the patterning of LM and as the physical scaffold for adhesive hydrogels. The unique porous architecture of the PP provides a natural template for the integration of LM and hydrogels, which facilitates the creation of electronic devices with improved flexibility and adhesion. The diverse patterning of nickel (Ni)-doped LM on the rough and porous pomelo pith surface is facilitated by the attractive force of a magnetic field applied below. The adhesive pre-gel is readily drawn into the pores of the pomelo pith due to capillary action. The resulting LM/PP hydrogel electronics are capable of rapid and stable Joule heating behavior and reliable motion detection. Additionally, the incorporation of glycerol endows this e-skin with superior freezing and desiccation resistance. Thus, this facile fabrication strategy successfully integrates excellent conductivity, adhesion, and environmental resilience, offering a promising paradigm for advanced wearable electronics.

An injectable, rapidly photo-crosslinkable hybrid hydrogel with temporally coordinated release and attenuation of inflammatory activation for potential extraction socket management.