Zehuan Huang

Effective hemorrhage control and wound closure are frequently compromised by the poor shape adaptability of preformed bulk hydrogel dressings, which fail to maintain intimate contact with irregular, bleeding tissue. To address this, we developed a freeze-dried polyelectrolyte complex powder (GLF-K) composed of dopamine-grafted γ-poly-l-glutamic acid, ε-poly-l-lysine, keratin, and iron ions. The network architecture relies on primary electrostatic cross-linking, synergistically reinforced by dopamine-Fe3+ coordination, which enables the GLF-K powder to rapidly rehydrate and transition into a cohesive hydrogel upon exposure to moisture. Compared to commercial chitosan hemostats, the GLF-K powder exhibited comparable or enhanced hemostatic efficacy in both in vitro and in vivo hemorrhage models, alongside excellent biocompatibility. More importantly, in a full-thickness skin defect model, GLF-K treatment accelerated the early-stage healing rate to 55.8% by day 3, significantly outperforming the control group. These findings suggest that GLF-K powder represents a promising integrated platform for managing acute hemorrhage and promoting expedited wound healing in irregular tissue defects.

Natural load-bearing tissues such as tendon exhibit both high stiffness and toughness owing to their densely packed, hierarchical architectures. However, most synthetic hydrogels suffer from biomechanical mismatch and lack of biocompatibility, which restrict their utility in tendon-related therapy. In this work, we report a set of glassy, poly(vinyl alcohol) hydrogels, stiffened and toughened through salting-out with a super-kosmotropic salt, sodium hexametaphosphate. The highly-charged anion displays an exceptional B-coefficient of 1.408 L mol⁻¹ with remarkable kosmotropic effect, which not only promotes the formation of crystalline domains but also immobilizes free water molecules within gel networks. The resultant materials are endowed with substantially enhanced stiffness, toughness and fracture energy of 1061.8 MPa, 548.5 MJ m⁻³, and 272.5 kJ m⁻², respectively, matching those of native tendons. Utilizing these hydrogels as biomechanical scaffolds in a tendon-ruptured rat model demonstrate high efficacy in both morphological and functional recovery. Salting-out biopolymers with super-kosmotropic agents enlightens the design and construction of stiff-yet-tough biomaterials, holding great promise for biomedical applications in regenerative and reparative therapies of natural load-bearing tissues.

Polymer networks possess numerous elastically defective and isolated loops, which do not contribute to mechanical stiffness. In this report, we introduce a strategy of supramolecular topological linking to access stiffer‐yet‐ductile polymeric materials through incorporation of supramolecular tetravalent crosslinkers. Dynamic dissociation/re‐association between these high‐functionality crosslinks enables the formation of topologically‐linked loops that serve as elastic springs to stiffen the networks. An exceptional scaling exponent of 2.05 for Young's modulus versus crosslinker concentration is obtained, exceeding most reported randomly‐crosslinked polymeric systems. Compared to conventional analogs, the mechanical properties of the resultant materials are enhanced: Young's modulus (2‐fold), elongation at break (8‐fold), and work of fracture (100‐fold). Uplifting modulus scalings through supramolecular topological linking paves a new path to the design of stiffness‐reinforced soft materials, holding substantial promise in load‐bearing application scenarios such as tissue implants, bioelectronic interfaces, and soft robotics.

Polymer networks possess numerous elastically defective and isolated loops, which do not contribute to mechanical stiffness. In this report, we introduce a strategy of supramolecular topological linking to access stiffer‐yet‐ductile polymeric materials through incorporation of supramolecular tetravalent crosslinkers. Dynamic dissociation/re‐association between these high‐functionality crosslinks enables the formation of topologically‐linked loops that serve as elastic springs to stiffen the networks. An exceptional scaling exponent of 2.05 for Young's modulus versus crosslinker concentration is obtained, exceeding most reported randomly‐crosslinked polymeric systems. Compared to conventional analogs, the mechanical properties of the resultant materials are enhanced: Young's modulus (2‐fold), elongation at break (8‐fold), and work of fracture (100‐fold). Uplifting modulus scalings through supramolecular topological linking paves a new path to the design of stiffness‐reinforced soft materials, holding substantial promise in load‐bearing application scenarios such as tissue implants, bioelectronic interfaces, and soft robotics.

Supramolecular polymer networks are transiently cross-linked soft materials that have exceptional material properties such as high toughness, contractility, and recyclability. Previous studies have focused on optimizing their uniaxial mechanical features but did not manage to impart them with biaxial ductility. Here, we develop a set of biaxially ductile supramolecular polymer networks constructed by slow-dissociative, noncovalent cross-linkers. Retarding cross-link dissociation kinetics enables access of glass-like networks, exhibiting both enhanced compressibility and biaxial stretchability. Dynamic dissociation/reassociation of transient cross-linking junctions benefits to address biaxial deformation locking, thus achieving a compressive strength of more than 160 megapascals and a large areal strain up to 10,000%. A universal method of quantifying biaxial mechanical properties for supramolecular networks is also reported. This work enlightens the design and construction of biaxially ductile polymeric materials, holding substantial promise in applications including bioelectronic interfaces, soft robots, and tissue implants.

Achieving sensitive and reversible responsivity over physiologically relevant pH ranges (4.5-7.5) remains of great interest for the design of next-generation autonomous drug delivery devices. Developing molecular interactions that are responsive within this pH range would enable targeted drug delivery at tumor sites or within inflamed or arthritic joints, where these changes in pH occur. Here, we demonstrate pH-responsive molecular interactions by the kinetic locking of host-guest complexes. Employing these complexes as dynamic crosslinks within polymer networks gives rise to materials with highly pH-responsive mechanical and viscoelastic properties. These systems further exhibit pH-dependent release of cargo, offering a self-responsive approach toward targeted drug delivery.

Tumor recurrence and metastasis after surgery are important factors affecting patient survival. The immunosuppressed tumor microenvironment after surgery reduces the ability of the immune system to clear residual tumor cells, thus increasing the risk of recurrence and metastasis. Currently, immunotherapy-based adjuvant therapy can effectively inhibit tumor recurrence and metastasis after surgery, but simultaneous and efficient synergistic activation of adaptive and innate immunity is a challenge. Here, we utilized polymeric hydrogel loaded with decitabine (DAC), cisplatin (CDDP) and manganese ions (Mn²⁺) as a postoperative filler immunogel to synergistically activate both anti-tumor innate and adaptive immunity. The sustained release of CDDP and DAC burst gasdermin E (GSDME)-mediated pyroptosis and activated adaptive immunity, while Mn²⁺ enhanced intrinsic immune activation through STING pathway. Such immunogel achieved an encouraging anti-tumor effect with an 80 % total survival rate for recurrent tumors and a 60 % survival rate for metastatic tumors. Considering that this in situ immunogel possesses simple formulation and displays superior anti-tumor effect, this research provided a promising strategy for postoperative cancer therapy.

Molecular hinges are ubiquitous in both natural and artificial supramolecular systems. A major challenge to date, however, has been simultaneously achieving high thermodynamic and kinetic stability. Here, we employ host-enhanced intramolecular charge-transfer interactions to mediate entropy-favored complexation between a flexible AB₂-type guest and a macrocyclic host, forming a new type of molecular hinge with an ultrahigh picomolar binding affinity (K_a > 10¹² M^-1). This entropy-promoted hinge modulates photoisomerization, exhibiting a substantial preference for the E-isomer, which is further demonstrated to mirror the natural retinal-opsin cycle, promoting the sensitization of visible light. This work unveils an efficient approach to exploit entropy-dominant architectures for the design of hierarchical molecular systems.

The evolution of flexible sensors heavily relies on advances in soft-material design and sensing mechanisms. Supramolecular chemistry offers a powerful toolbox for manipulating nanoscale and molecular structures within soft materials, thus fostering recent advancements in flexible sensors and electronics. Supramolecular interactions have been utilized to nanoengineer functional sensing materials or construct chemical sensors with lower cost and broader targets. In this perspective, we will highlight the use of supramolecular interactions to regulate and optimize nanostructures within functional soft materials and illustrate their importance in expanding the nanocavities of bioreceptors for chemical sensing. Overall, a bridge between tissue-mimicking flexible sensors and cell-mimetic supramolecular chemistry has been built, which will further advance human healthcare innovation.

Recent progress in the development of synthetic polymer networks has enabled the next generation of hydrogel-based machines and devices. The ability to mimic the mechanical and electrical properties of human tissue gives great potential toward the fields of bioelectronics and soft robotics. However, fabricating hydrogel devices that display high ionic conductivity while maintaining high stretchability and softness remains unmet. Here, we synthesize supramolecular poly(ionic) networks, which display high stretchability (>1500%), compressibility (>90%), and rapid self-recovery (10 ¹³ M ⁻² ). Superior adherence between layers enabled the fabrication of an intrinsically stretchable hydrogel power source, paving the way for the next generation of multi-layer tissue mimetic devices.