Lei Ye

Subretinal fibrosis (SRF), a severe vision-threatening complication secondary to neovascular age-related macular degeneration (nAMD), remains a major clinical challenge due to its complex pathogenesis and prolonged disease course. The fibrotic process is driven by multiple synergistic factors, including chronic inflammation, hypoxia, epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, and pathological neovascularization, which collectively lead to the ineffectiveness of conventional anti-vascular endothelial growth factor (VEGF) monotherapies in halting disease progression. This study developed a sequential dual-drug delivery system based on the terpolymer P(NIPAM-co-AA-co-HEMA) hydrogel (NAHGel), designed to achieve multi-targeted regulation from the pathological microenvironment to downstream fibrotic processes. NAHGel exhibits excellent thermal responsiveness, biomechanical stability, and biodegradability, and is co-loaded with matrine (MT) and cRGD-modified sorafenib liposomes (SF/cLP). The hydrogel undergoes thermal contraction to enable the rapid release of hydrophilic MT, exerting anti-inflammatory and anti-hypoxic effects. As the hydrogel progressively degrades, SF/cLP is released in a delayed manner and, under cRGD mediation, is targeted to RPE cells and vascular endothelial cells. This enables modulation of key pathways including TGF-β2/MEK1/2/ERK1/2 and HIF-α/VEGF/PDGF, thereby inhibiting EMT and endothelial proliferation. In a laser-induced SRF mouse model, MT + SF/cLP@NAHGel formed a stable in situ gel within 24 h after intravitreal injection and remained structurally intact in the dynamic vitreous environment, enabling sustained retention for up to 8 months. Imaging and histological analyses demonstrated that, compared with aflibercept and other group, this system significantly reduced choroidal neovascularization and fibrotic lesion areas. Transcriptomic analysis further confirmed its broad inhibition of signaling pathways related to inflammation, angiogenesis, and fibrosis, with marked downregulation of key mediators including VEGFA, TGF-β2, TNF-α, and HIF-1α. MT + SF/cLP@NAHGel achieves sequential drug release and multi-targeted synergy to intervene in key pathological processes such as inflammation, hypoxia, EMT, and pathological neovascularization, thereby effectively halting SRF progression. Combining sustained therapeutic efficacy with excellent biosafety, this system holds strong translational potential as a long-acting treatment strategy for SRF and other multifactorial retinal diseases.

A dual-level interface stabilization strategy enables a green one-pot synthesis of EGaIn-reinforced hydrogels with excellent performance for real-time motion monitoring and infrared camouflage.

Spinal cord injury (SCI), a highly disabling injury to the central nervous system, has a complex and sequential pathogenesis. Traditional multiple‐delivery systems rely on a physical mix of nanoparticles or drugs in hydrogels, which lacks the controllability of the drug. To solve these problems, an integrative hydrogel system cross‐linked with a Per‐g‐PSB nanogel is designed. Dendritic macromolecular nanogels (Per‐g‐PSB) could not only act as cross‐linkers to adjust the hydrogel mechanical properties but also form a dynamic network (Dex/Per‐g‐PSB hydrogel). Most importantly, a large amount of charge could lead to a significant sustained release via electrostatic interactions. The hydrogel platform (Mel/Ibu@D/P‐g‐PSB) realizes the sequential release of melatonin and ibuprofen by different mechanisms. Melatonin is first released by diffusion and exhibits significant neuroprotective effects during the acute phase by downregulating the expression of inflammatory cytokines. Ibuprofen is released in the second stage due to strong electrostatic interactions, and it reduces RhoA signaling activation by blocking the ROCK pathway in the subacute phase, which reduces the deleterious cascade reaction after spinal cord injury. These results show that the ion‐sensitive hydrogel platform with sequentially releasing drug effects, combining anti‐inflammatory effects and blocking the ROCK pathway, shows excellent repair of SCI.

In recent years, zwitterionic materials have been widely used in biomedical and nanomedical materials due to their unique structure in which the molecule is electrically neutral with equal positive and negative charge. This kind of material could form a thick hydration layer by the electrostatic effect, prevent contamination, and show wide applications in biomedical and life science fields, such as resisting non-specific protein adsorption, biofilm, thrombosis formation, and so on. Most importantly, the diversity of functional groups has made it more convenient for surface modification and further utilization, creating multifunctional materials for various applications. This review summarized the up-to-date zwitterionic materials, including the conventional and novel zwitterionic materials and their structural characteristics, as well as the applications in blood-contacting and implantable devices, antibacterial coatings, wound dressings, drug-targeted carriers, and smart wearable biosensors, especially in the biomedical and clinical uses. New discoveries, existing challenges, and the commercial status of zwitterionic materials are also outlined, and their future opportunities and development perspectives as new novel biomaterials are demonstrated.

The application of wearable sensors is becoming increasingly widespread, among which hydrogels, with their excellent biocompatibility, multifunctionality and modulus similar to human skin, are considered one of the most promising wearable sensors. However, when using hydrogel flexible sensors adhering to human skin, unnecessary adhesion often occurs, resulting in operational difficulties and unstable signal collection. Moreover, the hydrogel polymerization process is time-consuming and difficult to perform. Based on this, we have prepared an asymmetric adhesive dual-layer conductive hydrogel that can be rapidly prepared to address the above issues. Introducing ZnCl₂ into a solution of tannic acid (TA) coated diatomaceous earth (DE) forms a self-catalytic system, allowing the hydrogel to be prepared within 15 seconds. The components ZnCl₂ and TA endow the system with lower freezing temperature and strong adhesion properties. By adjusting the ratio accordingly, a dual-layer hydrogel consisting of an asymmetrical structure could be prepared facilely. The adhesive side can firmly adhere to human skin and can be removed easily without leaving any residue, while the non-adhesive side can prevent it from sticking to fingers or clothing and contamination, facilitating stable signal transmission. The dual-layer hydrogel developed in this study possesses many advantages such as rapid gelation, asymmetric adhesion, strong interfacial force, mechanical reinforcement and anti-freezing properties. It can stably monitor a wide range of strains and daily human movements, with broad application prospects, providing a new approach for the development of functional flexible devices.

This work presents a multifunctional MXene-composited organohydrogel with high tensile strength, excellent environmental stability, recyclability and outstanding UV-shielding ability for flexible wearable sensors.

Surgical resection remains the most common method of tumor treatment; however, the high recurrence and metastasis after surgery need to be solved urgently. Herein, we report an injectable zwitterionic hydrogel based on "thiol-ene" click chemistry containing doxorubicin (DOX) and a macrophage membrane (MM)-coated 1-methyl-tryptophan (1-MT)-loaded polyamide-amine dendrimer (P-DOX/1MT) for preventing the postoperative recurrence of tumors. The results indicated that P-DOX/1MT@MM exhibited enhanced recognition and uptake of the dendrimer by tumor cells and induced the immunogenic cell death. In the mice tumor model, the P-DOX/1MT@MM-Gel exhibited high therapeutic efficiency, which could significantly reduce the recurrence of the tumor, including suppressing tumor growth, promoting dendritic cell maturation, and increasing tumor-infiltrating cytotoxic T lymphocytes. The mechanism analysis revealed that the hydrogel greatly reduces the side effects to normal tissues and significantly improves its therapeutic effect. 1MT in the hydrogel is released more rapidly, improving the tumor suppressor microenvironment and increasing the tumor cell sensitivity to DOX. Then, the DOX in the P-DOX/1MT@MM effectively eliminatedo the residual tumor cells and exerted enhanced toxicity. In conclusion, this novel injectable hydrogel that combines chemotherapy and immunotherapy has the property of sequential drug release and is a promising strategy for preventing the postoperative recurrence of tumors.