Yun-Long Wu

Dry eye disease (DED) is a multifactorial disorder characterized by intricate pathogenesis, necessitating a multi‐target synergistic intervention strategy. Current anti‐inflammatory drugs for DED are limited by low bioavailability, ocular irritation, and inadequate relief. Herein, we propose a multifunctional hydrogel encapsulating Mizoribine, a small‐molecule water‐soluble immunosuppressant. The formulation undergoes in situ gelation on the ocular surface, forms a mucin‐adhered coating, and responds to pathological oxidative stress to enable controlled drug release. In vitro studies demonstrate the formulation effectively mitigates cellular oxidative stress by scavenging ROS and upregulating antioxidant factors. It also protects mitochondrial function, reduces apoptosis, and modulates macrophage polarization. In vivo, topical application of the hydrogel markedly alleviates clinical signs of disease. It also suppresses ocular surface inflammation and reverses conjunctival goblet cell loss. Molecular and cellular analyses indicate the hydrogel exerts its therapeutic effects primarily through antioxidative, anti‐inflammatory, and macrophage‐modulating mechanisms. Importantly, the formulation exhibits an excellent biosafety profile. Our findings highlight that this multifunctional hydrogel serves as a potent, convenient, and safe nanotherapeutic platform. By integrating ROS‐responsive, thermosensitive, and sustained drug‐release properties with antioxidant, anti‐inflammatory, and immunomodulatory functions, this formulation simultaneously targets multiple pathological pathways, offering a promising avenue for clinical translation in treating chronic ocular surface diseases.

From a delivery-control perspective, this review shows how stimuli-responsive nanocarriers regulate channel modulators and artificial ion channels for precision therapy.

Current myocardial infarction (MI) biomaterials often fail to dynamically adapt to the evolving pathological microenvironment (e.g., ROS bursts, hypoxia), lacking both mechanical compatibility and in situ feedback. To overcome these limitations, we developed an albumin hydrogel platform (BST) with a closed‐loop pathological response system. BST is a pH‐responsive hydrogel, functionalized with MRI/CT probes and loaded with mitochondria‐targeted CAT‐SOD enzyme nanogels (CSDT). It forms a self‐repairing scaffold with high shear viscosity (∼300 Pa·s), elasticity, and cardiac‐like mechanics (∼7.5 kPa), stabilizing the infarct wall. Hypoxia‐induced acidosis triggers the release of CSDT nanogels and albumin, enabling mitochondrial ROS scavenging and O ₂ generation, while albumin restores tissue osmotic balance. These actions collectively alleviate oxidative stress, modulate immune responses, and promote cardiomyocyte survival by enhancing autophagy and anti‐apoptotic pathways. This inside‐out feedback mechanism reverses oxidative stress and hypoxia, shifts macrophages to a reparative M2 phenotype, and increases angiogenesis by ∼2.5‐fold. In an MI mouse model, BST, with programmable biodegradation (∼3 weeks), restored left ventricular ejection fraction to ∼70% of sham group and improved 28‐day survival by ∼2.5‐fold. Furthermore, BST enables real‐time MRI/CT tracking of material retention and tissue repair dynamically, permitting spatiotemporal control of the infarct microenvironment and advancing precision MI therapy toward clinical translation.

Organoids hold great promise for modeling development, disease, and patient-specific therapy, but their translation is limited by poor vascularization, lack of immune and neural components, low reproducibility, and difficulties in scale-up. 3D bioprinting can address these bottlenecks by enabling digitally guided, spatially precise deposition of bioinks to construct multiscale architectures and perfusable channel networks, yet matching printing principles with material systems remains a central challenge. Unlike existing reviews that focus on isolated technologies or materials, this review introduces a cohesive paradigm that systematically links assembly mechanisms, material properties, and organoid functions along a mechanism–material–function axis. Its core breakthrough shifts the field from empirical guesswork to on-demand engineered design. We analyzed physicochemical mechanisms, such as ionic crosslinking, hydrophobic interactions, dynamic covalent bonding, and photoinitiated polymerization, and mapped them to tunable metrics, including modulus, degradation kinetics, mass-transport capacity, and bioactive delivery. Based on this mapping, we developed a full-chain decision framework for technology selection, material design, and process-parameter optimization, and proposed a predictive, reproducible formulation strategy. By transforming organoid fabrication from an empirical practice into an engineering discipline, this framework enables predictable and scalable organoid fabrication for regenerative medicine, drug discovery, and disease modeling applications through standardized process-parameter optimization and material recipe design.

Extracellular matrix (ECM) is a multifaceted network that encases cells, composed of various polysaccharides, proteins, and adhesion molecules, etc. It plays a critical role in providing structural support to cells and regulating essential cellular activities such as proliferation, migration, and differentiation. Due to these functions, decellularized extracellular matrix (dECM) has attracted considerable interest in biomedicine and holds promising application potential. However, simple dECM materials are often insufficient to meet the diverse demands of different physiological or pathological microenvironments. Recently, composite materials made from biomaterials and dECM have emerged as a solution, significantly enhancing the biological functions and clinical applicability of dECM. By using different material preparation techniques, these composite materials can be endowed with specific properties, enabling them to better meet the requirements of various biomedical applications. In this review, the preparation techniques for various dECM‐based composite biomaterials, including physical crosslinking, chemical modification, 3D printing, and electrospinning, are summarized. Different types of dECM‐based composites are also classified, and their biological and material properties are discussed, highlighting their suitability for specific biomedical applications. This review aims to provide a comprehensive reference for the development and clinical translation of dECM‐based biomaterials, from preparation to application.

Periodontitis is a chronic inflammatory disease characterized by hypoxia, excessive oxidative stress, and immune dysregulation, leading to tissue destruction and bone resorption. Although antioxidants can reduce ROS and inflammation, most lack specificity and have a short residence time, limiting their effectiveness. Since mitochondria are the primary source of ROS, targeting mitochondrial ROS is a promising strategy for periodontitis treatment. However, this alone cannot address the complex “ROS‐inflammation‐hypoxia” cycle in periodontitis, requiring a more comprehensive approach. Here, a natural enzyme cascade nanogel (TPP‐SAT) composed of triphenylphosphine (TPP), superoxide dismutase (SOD), and catalase (CAT) via in‐situ polymerization is developed. TPP‐SAT targets mitochondrial ROS, converting ROS (such as H ₂ O ₂ or ·O ₂ ⁻ ) into O ₂ through the enzyme cascade of SOD and CAT. This alleviates hypoxia, prevents oxidative damage, and restores the balance between pro‐inflammatory M1 and anti‐inflammatory M2 macrophages, reducing inflammation and immune dysfunction. TPP‐SAT breaks the “ROS‐inflammation‐hypoxia” cycle, inhibits alveolar bone resorption, and accelerates periodontal tissue regeneration. This approach offers a promising strategy for treating periodontitis and other chronic inflammatory diseases, with strong clinical potential.