Severe trauma and uncontrolled bleeding remain major clinical challenges, requiring materials that can rapidly seal wounds under wet and dynamic conditions. Here, we report a self-gelling hemostatic powder based on quaternized chitosan (QCS) and oxidized konjac glucomannan (OKGM), which achieves rapid blood-to-gel transformation through a synergistic mechanism combining electrostatic attraction and Schiff base cross-linking. Upon contact with blood, the powder instantaneously absorbs exudate and self-assembles into a cohesive hydrogel barrier, exhibiting strong wet tissue adhesion (52.87 kPa) and high burst pressure resistance (33.37 kPa). The positively charged QCS component promotes erythrocyte aggregation and coagulation, while dynamic covalent bonding between QCS and OKGM ensures structural stability and self-healing. In a rat liver hemorrhage model, the material significantly reduced blood loss and hemostatic time compared to commercial controls. Additionally, QCS-OKGM powder (QOM) demonstrated broad-spectrum antibacterial activity (>98% inhibition) and immunomodulatory effects, promoting macrophage polarization toward the anti-inflammatory M2 phenotype. In vivo examination in a rat skin wound model demonstrated that QOM significantly promoted wound healing by modulating the local inflammatory phenotype. This electrostatic-Schiff synergistic strategy provides a paradigm for developing next-generation bioactive powders capable of instant blood gelation, rapid hemostasis, and immune microenvironment regulation.

Severe burn wounds are highly susceptible to bacterial infection due to the loss of the skin barrier, which significantly impedes healing and increases mortality. Developing advanced dressings that combine potent antimicrobial activity with tissue regeneration is therefore of great clinical importance. In this study, a multifunctional nanofibrous dressing (BBR/P@Fe NFs) was constructed by co-loading berberine (BBR) and a polydopamine‑iron coordination complex (P@Fe) into gelatin-based nanofibers via electrospinning. Experimental results indicate that the BBR/P@Fe NFs achieve strong tissue adhesion and rapid hemostasis by employing the polydopamine-mediated mussel-inspired adhesion mechanism, and generate a potent antibacterial effect through the photothermal-chemical synergistic antibacterial strategy. Additionally, BBR/P@Fe NFs can facilitate angiogenesis and reduce inflammation to promote skin regeneration in severely burned wounds with bacterial infections. These findings confirm that the biomimetic BBR/P@Fe NFs constitute a promising multifunctional platform that can address the clinical challenges of treating severely infected burns.

Pathological bone defects remain formidable clinical challenges due to their dynamically hostile microenvironments, typified by chronic inflammation, acidosis, hypoxia, and oxidative stress. Conventional therapeutic strategies, dependent on static scaffolding and passive drug release, often fail to meet the demand for precise and adaptive intervention. Emerging adaptive smart hydrogels, endowed with dynamic regulatory capabilities, are reshaping the paradigm of bone repair by enabling spatiotemporally controlled drug delivery, degradation, immunomodulation, and cellular regulation. Harnessing both physical triggers (light, temperature, electricity, magnetism, ultrasound) and chemical/biological cues (pH, redox, enzymatic activity), these hydrogels provide real-time responsiveness and targeted therapeutic action. This review discusses the pathological contexts of bone defects and systematically elaborates on the dynamic regulatory mechanisms of adaptive hydrogels while highlighting their innovative applications in diabetic bone defects, bone tumors, osteoporosis, osteoarthritis, and periodontitis. We further emphasize their roles in precision immunomodulation, osteogenesis, and tumor inhibition. Finally, we outline key challenges and propose future directions, including personalized design strategies, multimodal integration, and convergence with bioelectronics and AI-assisted material design, to accelerate clinical translation. This work aims to inspire interdisciplinary innovation and guide the development of intelligent hydrogel-based strategies for precision bone healing in complex pathological contexts.

Conductive hydrogels are widely recognized for their flexibility and biocompatibility, making them ideal for soft electronics and health monitoring. However, due to the lack of recyclability of current hydrogel materials, environmental problems arise, thereby restricting the application of sensors. This study, through the integration of oxidized starch, gelatin, mesoporous glass nanoparticles (MBGNs), and MXene materials, developed a recyclable and degradable GOMM hydrogel material, which, when successfully built, could be used for exercise and a variety of physiological health flexible wearable sensors. This hydrogel, formed through noncovalent cross-linking (hydrogen bonds and Schiff base bonds), demonstrates excellent adhesion (53.49 kPa on pig skin). The high electrical conductivity of MXene endowed the GOMM hydrogel with excellent electrical conductivity (5.05 mS/cm). Moreover, the existence of MBGNs provides a large number of cross-linking points for hydrogels, which further optimizes the mechanical properties of hydrogels (247.22%). Notably, the hydrogel degrades in phosphate-buffered salinle solution within 24 days (the degradation rate reaches 92%), addressing electronic waste concerns. Based on the above excellent performance, when assembled into wearable sensors, it can achieve multiscenario applications (strain, temperature, humidity, electromyogram, and electrocardiogram signals) and health monitoring. Furthermore, the hydrogel is recyclable and can be thermally reprocessed, offering an ecofriendly solution for next-generation soft electronics in medical diagnostics and wearable technologies.

Natural active components, such as polyphenols, possess significant potential for application in the medical field. However, poor solubility, low stability and insufficient bioavailability seriously restrict application efficiency. We constructed a carrier-free nanoplatform to achieve efficient co-loading and functional synergy of hydrophobic eugenol (Eu) and hydrophilic tannic acid (TA). The Eu and TA self-assembled to form a nanoemulsion through non-covalent interactions, and further coordination cross-linking between Zn2+ and TA was utilized to prepare Eu-TA-zinc chloride nanospheres (Eu-TA-ZC NSs). The Eu-TA-ZC NSs exhibited uniform particle size, regular morphology, strong antioxidant activity and efficient antibacterial effects. This study not only overcomes the delivery problems of natural active components and enhances their performance, but also provides a novel strategy for developing efficient multifunctional co-delivery systems.

Radiotherapy (RT) is widely used as an adjuvant treatment after surgical resection for osteosarcoma, but its efficacy is often limited by insufficient radiosensitization and an immunosuppressive tumor microenvironment that restricts systemic antitumor immunity and promotes recurrence and metastasis. Here we report an injectable metal-drug supramolecular condensate formed from hafnium ions and alendronate (Hf-ALN) and loaded with the COX-2 inhibitor celecoxib (CXB) for synergistic radioimmunotherapy of postoperative osteosarcoma. The condensate forms through coordination-driven liquid-liquid phase separation between Hf4+ ions and alendronate, enabling local retention within postoperative bone defects and sustained therapeutic release. Upon X-ray irradiation, the Hf component amplifies radiation energy deposition and reactive oxygen species generation, thereby enhancing radiation-induced DNA damage and immunogenic cell death. Meanwhile, the acidic tumor microenvironment triggers responsive release of CXB and ALN; CXB inhibits the COX-2/PGE2 immunosuppressive pathway, while ALN promotes macrophage repolarization toward the M1 phenotype, collectively remodeling the tumor immune microenvironment. This strategy enhances dendritic cell maturation, activates cytotoxic CD8+ T cells, and reduces regulatory T-cell infiltration. In orthotopic osteosarcoma models, CXB@Hf-ALN combined with RT suppresses tumor recurrence, preserves bone integrity, inhibits pulmonary metastasis, and prolongs survival with minimal systemic toxicity, offering a promising strategy to improve postsurgical RT outcomes in osteosarcoma.

Diabetic wounds exhibit elevated ROS, which aids in pathogen clearance, but it also worsens inflammation and tissue damage. Precise temporal regulation of ROS is therefore critical to healing, but traditional dressings lack such dynamic capabilities. Herein, we designed a microenvironment-responsive nanofiber (GC/G NF) through the electrospinning process. After absorbing wound exudate, this nanofiber transforms from a fiber-like structure into a 3D network hydrogel that firmly adheres to the skin. More significantly, the system can dynamically and precisely modulate the amount of ROS in wounds by intelligently switching between multiple enzymatic cascade catalytic systems, facilitating programmable diabetic wound healing. During the first stage of bacterial infection, GC/G NF initiates a GOx/POD-like cascade to produce ROS, while near-infrared laser irradiation provides a thermal effect. This synergy enables effective biofilm removal, bacterial killing, and reduction of local blood glucose levels. During the proliferation stage, it switches into a SOD/CAT-like cascade to scavenge excess ROS accumulated from the previous infection, effectively relieving oxidative stress and providing oxygen support, thereby reducing inflammation and enhancing angiogenesis and cell proliferation. In this work, we developed a temporally-programmed multifunctional adaptive ROS-regulating platform that can effectively improve the complex wound microenvironment in diabetes and provide new therapeutic approaches.

High-strength and reusable adhesives are essential for many applications but are often limited by the trade-off between strength and detachability, as well as recyclability. Here, we introduce a high-strength supramolecular adhesive with adhesion strengths exceeding 1 MPa (up to 4.65 MPa) and remarkable detachability, achieving a switchability ratio of up to 1800. These outstanding performances are enabled by synergistically tuning interfacial physical bonds and bulk modulus of a hydrogen-bond-and-dipole-dipole-enriched polymer (HyDiP). In its dehydrated state, the adhesive exhibits high modulus (445 MPa) and exposes rich surface bonding groups, yielding robust adhesion on various surfaces. In its rehydrated state, the modulus decreases to 0.11 MPa and the physical bond density on the surface is significantly reduced, allowing easy detachment. Furthermore, the HyDiP adhesive is transparent when dehydrated, recyclable and removable, ideal for sustainable applications like adaptive grippers and superglue for heavy loads.

Flexible electronics have been rapidly advancing and have garnered significant interest in monitoring physiological activities and health conditions. However, flexible electronics are prone to detachment in humid environments, so developing human-friendly flexible electronic devices that can effectively monitor human movement under various aquatic conditions and function as flexible electrodes remains a significant challenge. Here, we report a strongly adherent, self-healing, and swelling-resistant conductive hydrogel formed by combining the dual synergistic effects of hydrogen bonding and dipole-dipole interactions. The hydrogel has a commendable linear operating range (∼200% strain, GF = 1.44), stability of electrical signals for 200 cycles, excellent conductivity (2.18 S m-1), self-healing properties (∼30 min), and durable underwater adhesion stability. The conductive hydrogel can be developed into a flexible electronic sensor for detecting motion signals, such as joint flexion and swallowing, as well as for real-time underwater communication using Morse code. Additionally, the integration of this polymer with a low contact impedance facilitates real-time, high-fidelity detection of electroencephalogram (EEG) signals, serving as a flexible electrode. It is believed that our hydrogel will have good prospects in future wearable electronics.

Guided Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR) are essential surgical techniques in periodontal therapy, employing barrier membranes to prevent soft tissue infiltration and create a conducive environment for bone regeneration. However, the regenerative performance of conventional barrier membranes remains limited due to poor interface management and insufficient biological functionality. Recent developments have introduced the concept of Janus membranes-structures with asymmetric, dual-function surfaces-offering promising solutions to these challenges. While various reviews have addressed barrier membranes for periodontal and bone regeneration, comprehensive reviews specifically focusing on multifunctional Janus membranes are still limited. This review highlights recent advances in Janus membrane design for GTR and GBR applications. It first outlines key structural configurations, followed by an in-depth analysis of fabrication techniques and functional strategies, including osteogenesis promotion, antibacterial activity, and immunomodulation. By summarizing current progress and challenges, this review offers valuable insights into next-generation biomaterial development for periodontal regeneration. Looking forward, Janus membranes represent a compelling avenue for enhancing clinical outcomes in GTR and GBR procedures.

Diabetes is associated with excessive inflammation, which negatively impacts the fracture healing process and delays bone repair. Previously, growing evidence indicated that activation of the nod-like receptor (NLR) family, such as nod-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome induces a vicious cycle of chronic low-grade inflammatory responses in diabetic fracture. Here, we describe the synthesis of a bone adhesive hydrogel that can be locally injected into the fracture site and releases a natural inhibitor of NLRP3 (rutin) in response to pathological cue reactive oxygen species activity (ROS). The hydrogel (denoted as RPO) was facilely formed by the cross-linking of rutin-functionalized gelatin, poly(vinyl alcohol), and oxidized starch based on the dynamic schiff base and boronate ester bond. Specifically, rutin is conjugated in the RPO hydrogel via a ROS linker and is released as the linker is cleaved by active ROS. In vitro studies demonstrate that RPO hydrogel effectively mitigates oxidative stress, alleviates mitochondrial dysfunction, and limits the overactivation of NLRP3 inflammasome in bone marrow derived macrophages, thereby promoting osteogenic differentiation of bone marrow mesenchymal stem cells. In a diabetic rat fracture model, RPO hydrogel significantly accelerates bone repair by modulating the inflammatory microenvironment. Our results demonstrate that local, on-demand NLRP3 inhibition for the treatment of diabetic fracture is achievable by using an injectable bioresponsive adhesive RPO hydrogel.

Current treatments for osteoporotic fractures primarily target bone-resorbing osteoclasts, but they often fail to address fibrosis-a buildup of fibrous tissue that disrupts bone healing. This fibrosis is frequently triggered by bisphosphonates, which, while effective in reducing bone loss, also activate fibroblasts and impair callus formation. Here we show that an injectable hydrogel bone adhesive composed of magnesium-alendronate metal-organic frameworks (Mg-ALN MOF) embedded in a gelatin/dialdehyde starch network can simultaneously suppress bone resorption and reduce fibrosis. The Mg-ALN MOF adhesive binds firmly to irregular bone surfaces and degrades under acidic osteoporotic conditions, gradually releasing Mg2+ ions. These ions competitively bind to sclerostin (SOST), thereby interrupting the SOST/TGF-β signaling pathway that promotes fibroblast activation and abnormal collagen deposition. This dual-action mechanism significantly enhances fracture healing, resulting in a 27.8% improvement in flexural strength. Our findings suggest a promising therapeutic strategy that combines mechanical support with targeted regulation of both bone resorption and pathological fibrosis.

Conductive hydrogels are promising candidates for next-generation wearable electronics due to their flexibility, biocompatibility, and ion-conductive properties. However, achieving a balance among electrical conductivity, mechanical robustness, interfacial adhesion, and environmental stability remains a key challenge. Herein, we present a multifunctional hydrogel synthesized via a one-pot free radical polymerization of acrylic acid, methacryloxyethyltrimethylammonium chloride, tannic acid, and calcium ions. The designed hydrogel exhibits ultrastretchability (strain up to 2900%) and strong interfacial adhesion (160.92 kPa) owing to a synergistic cross-linked network formed by hydrogen bonding, ionic complexation, coordination, and covalent interactions. Adhesion capacity remains above 80% after ten peel cycles, indicating persistent interfacial coupling. It exhibits two linear sensitivity regimes, with gauge factors of 1.9 below 300% strain and 2.5 up to 1000%, and maintains stable electrical performance over 300 cycles. Its high ionic conductivity (30.24 mS/cm) supports low-impedance signal transmission, while its intrinsic UV-shielding property, derived from the catechol chemistry of tannic acid, enables reliable outdoor operation. The hydrogel also exhibits a rapid response time of 65 ms, allowing accurate detection of dynamic biomechanical signals. This conductive hydrogel holds great promise for real-time monitoring of human motion and microexpressions, as well as for secure communication applications such as Morse code encryption. This hydrogel design offers a promising route toward next-generation wearable electronics with potential applications in smart healthcare, human-machine interaction, and secure communication.

The occurrence of bacterial keratitis (BK) presents a significant threat to ocular health, often leading to visual impairment. Currently, conventional antibiotic therapies tend to promote bacterial resistance and lack biocompatibility. Therefore, it is of great significance to develop an alternative product with safe and efficient antimicrobial properties. In this study, we developed a novel smart pH-responsive nano-antibacterial system (PM/Ag-Ce6@ZIF-8) based on a metal-organic framework (MOF), enabling specific bacterial targeting and photodynamic therapy. By utilizing bacteria-specific maltodextrin transport pathway, the intelligent nano-antibacterial modified with maltotriose can accurately discriminate between bacterial infection and normal tissue, specifically target the site of infection, and efficiently accumulate at the infection site to enhance safety and efficacy. Furthermore, the incorporation of silver nanoparticles enhances the effectiveness of MOF photodynamic therapy by effectively eradicating bacteria. The nano-antibacterial system exhibits potent inhibition of biofilm formation as well as antibacterial activity while demonstrating excellent in vitro and in vivo biocompatibility. In an animal model of bacterial keratitis, PM/Ag-Ce6@ZIF-8 exhibits superior antibacterial activity compared to Levofloxacin (LVFX) eye drops, significantly improving therapeutic outcomes for bacterial keratitis in mice. Hence, this intelligent nano-antibacterial platform holds promising potential for clinical applications in treating keratitis.

Osteoporotic fractures are notoriously difficult to heal due to an imbalance between osteoblasts and osteoclasts. Current treatments often have limited efficacy or adverse side effects, necessitating safer and more effective solutions. Here, we developed an injectable plant-derived phosphate coordination compound-based adhesive hydrogel (MgPA-Gel) to restore bone homeostasis by integrating magnesium ions (Mg2+)-phytic acid (PA) nanoparticles with aminated gelatin (Gel-NH2) and aldehydated starch (AS). This hydrogel can firmly adhere to irregular bone surfaces at the fracture site and degrades in the acidic osteoporotic microenvironment, releasing PA and Mg2+ to modulate osteoclast and osteoblast activity. PA inhibits osteoclastogenesis by promoting monocyte secretion of cellular communication network factor 1 (CCN1), which disrupts Receptor Activator of Nuclear Factor-κB Ligand (RANKL)-Receptor Activator of Nuclear Factor-κB (RANK) signaling, while Mg2+ enhances osteoblast differentiation from bone marrow stem cells. Hydrogel implantation synergistically augmented the fracture healing cascade in osteoporotic bone, achieving an 84.6% improvement in bending resistance compared to standalone intramedullary stabilization in ovariectomized (OVX) rats. This study highlights the potential of PA-based coordination compounds as a promising strategy for osteoporotic fracture treatment.

Although hydrogel‐based therapies have demonstrated promising results in treating volumetric muscle loss (VML), addressing diabetic skeletal muscle defects remains a major challenge due to the interplay of chronic inflammation and impaired regenerative capacity associated with diabetes mellitus. This study presents a novel multifunctional hydrogel bioelectronic conductor designed specifically for diabetic VML repair. The hydrogel, which self‐assembles from mannose receptor‐binding glucomannan, polydopamine‐functionalized conductive polypyrrole, and gelatin, mimics the mechanical properties of native muscle tissue while providing immunomodulatory and electrocoupling effects. Multiple crosslinking mechanisms, involving both dynamic covalent and noncovalent interactions, endow the hydrogel with enhanced tissue adhesion (adhesion strength of 69.41 kPa to soft tissue), elasticity (100% self‐recovery), and rapid self‐healing ability (less than 1 min). The electrically conductive hydrogel‐based elastic bioelectronics can reestablish effective electrical coupling with electroactive muscle tissue, while its intrinsic immunomodulatory properties induce M2‐type macrophage polarization to alleviate chronic inflammatory response. In a diabetic rat VML defect model, the hydrogel bioelectronic conductor facilitated effective immunomodulation, muscle regeneration, and functional recovery of injured VML. These results suggest that the integration of tissue‐mimicking mechanics with both immunomodulatory and conductive properties offers a promising therapeutic approach for diabetic skeletal muscle repair.

Hydrogel is a kind of material with high water content, good biocompatibility and extracellular matrix-like property, among which polypyrrole (PPy) conductive hydrogels have both physical characteristics and excellent conductivity of hydrogels themselves. Its conductivity can be used to detect electrical signals generated in biological systems and provide electrical stimulation to regulate the activities and functions of cells and tissues. These characteristics make it widely used in the biomedical field. The recent progress of PPy conductive hydrogels in biomedical field was reviewed in this paper. In terms of classification, according to the cross-linking mechanism of PPy and hydrogel matrix, the non-covalent cross-linked PPy conductive hydrogels and covalent cross-linked PPy conductive hydrogels were divided. The applications of PPy conductive hydrogels in the biomedical field (Skin damage repair, nerve repair, myocardial repair and flexible sensing, etc.) were mainly introduced, and the development trend and challenges of PPy conductive hydrogels in the biomedical field were discussed.

Piezoelectric hydrogel sensors are becoming increasingly popular for wearable sensing applications due to their high sensitivity, self-powered performance, and simple preparation process. However, conventional piezoelectric hydrogels lack antifreezing properties and are thus confronted with the liability of rupture in low temperatures owing to the use of water as the dispersion medium. Herein, a kind of piezoelectric organohydrogel that integrates piezoelectricity, low-temperature tolerance, mechanical robustness, and stable electrical performance is reported by using poly(vinylidene fluoride) (PVDF), acrylonitrile (AN), acrylamide (AAm), p-styrenesulfonate (NaSS), glycerol, and zinc chloride. In detail, the dipolar interaction of the PVDF chain with the PAN chain facilitates the crystal phase transition of PVDF from the α to β phase, which endows the organohydrogels with a high piezoelectric constant d33 of 35 pC/N. In addition, the organohydrogels are highly ductile and can withstand significant tensile and compressive forces through the synergy of the dipolar interaction and amide hydrogen bonding. Besides, by incorporating glycerol and zinc chloride, the growth of ice crystals is inhibited, allowing the organohydrogels to maintain stable flexibility and sensitivity even at -20 °C. The real-time monitoring of the pulse signal for up to 2 min indicates that the gel sensor has stable sensitivity. It is believed that our organohydrogels will have good prospects in future wearable electronics.