Exploring high‐efficiency reactive oxygen species (ROS)‐elimination materials is of great importance for combating oxidative stress in diverse diseases, especially stem‐cell‐based biotherapeutics. By mimicking the FeN active centers of natural catalase, here, an innovative concept to design ROS‐elimination artificial biocatalysts with Ru catalytic centers for stem‐cell protection is reported. The experimental studies and theoretical calculations have systematically disclosed the activity merits and structure diversities of different Ru sites when serving as ROS‐elimination artificial biocatalysts. Benefiting from the metallic electronic structures and synergetic effects of multiple sites, the artificial biocatalysts with Ru cluster centers present exceptional ROS‐elimination activity; notably, it shows much higher catalytic efficiency per Ru atom on decomposing H2O2 when compared to the isolated single‐atom Ru sites, which is more efficient than that of the natural antioxidants and recently reported state‐of‐the‐art ROS‐scavenging biocatalysts. The systematic stem‐cell protection studies reveal that the catalase‐like artificial biocatalysts can provide efficient rescue ability for survival, adhesion, and differentiation functions of human mesenchymal stem cells in high ROS level conditions. It is suggested that applying these artificial biocatalysts with Ru cluster centers will offer a new pathway for engineering high‐performance ROS‐scavenging materials in stem‐cell‐based therapeutics and many other ROS‐related diseases.

Hydrogels, which are hydrophilic polymer networks, have attracted great attention, and significant advances in their biological and biomedical applications, such as for drug delivery, tissue engineering, and models for medical studies, have been made. Due to their similarity in physiological structure, hydrogels are highly compatible with extracellular matrices and biological tissues and can be used as both carriers and matrices to encapsulate cellular secretions. As small extracellular vesicles secreted by nearly all mammalian cells to mediate cell–cell interactions, exosomes play very important roles in therapeutic approaches and disease diagnosis. To maintain their biological activity and achieve controlled release, a strategy that embeds exosomes in hydrogels as a composite system has been focused on in recent studies. Therefore, this review aims to provide a thorough overview of the use of composite hydrogels for embedding exosomes in medical applications, including the resources for making hydrogels and the properties of hydrogels, and strategies for their combination with exosomes.

Engineering a complete, physiologically functional, periodontal complex structure remains a great clinical challenge due to the highly hierarchical architecture of the periodontium and coordinated regulation of multiple growth factors required to induce stem cell multilineage differentiation. Using biomimetic self-assembly and microstamping techniques, we construct a hierarchical bilayer architecture consisting of intrafibrillarly mineralized collagen resembling bone and cementum, and unmineralized parallel-aligned fibrils mimicking periodontal ligament. The prepared biphasic scaffold possesses unique micro/nano structure, differential mechanical properties, and growth factor-rich microenvironment between the two phases, realizing a perfect simulation of natural periodontal hard/soft tissue interface. The interconnected porous hard compartment with a Young's modulus of 1409.00 ± 160.83 MPa could induce cross-arrangement and osteogenic differentiation of stem cells in vitro , whereas the micropatterned soft compartment with a Young's modulus of 42.62 ± 4.58 MPa containing abundant endogenous growth factors, could guide parallel arrangement and fibrogenic differentiation of stem cells in vitro . After implantation in critical-sized complete periodontal tissue defect, the biomimetic bilayer architecture potently reconstructs native periodontium with the insertion of periodontal ligament fibers into newly formed cementum and alveolar bone by recruiting host mesenchymal stem cells and activating the transforming growth factor beta 1/Smad3 signaling pathway. Taken together, integration of self-assembly and microstamping strategies could successfully fabricate a hierarchical bilayer architecture, which exhibits great potential for recruiting and regulating host stem cells to promote synergistic regeneration of hard/soft tissues.

Exploration of efficient antioxidase-like reactive oxygen nanobiocatalysts (ROBCs) is a major challenge in combating oxidative stress-related diseases. Herein, the molecularly well-defined Ru-porphyrin-networks (Ru-Por-Net)-based ROBCs with ultrafast and reversible redox-centers for catalytic elimination of reactive oxygen species (ROS) are reported. Owing to the large π-conjugated networks, Ru-N coordination structures, and unique electronic and redox properties of atomic Ru sites, the Ru-Por-Net-based ROBCs exhibit exceptional catalytic ROS-scavenging activities. It is considerably more efficient than recently reported state-of-the-art anti-ROS biocatalysts. Notably, a new nucleophilic attack pathway to eliminate H 2 O 2 and produce O 2 is proposed via theoretical calculations, and the desorption of the OO* process is identified as the rate-determining step of atomic Ru centers. Cellular studies reveal that the new ROBCs can efficiently secure the survival, adhesion, spreading, and differentiation of the stem cells in high-ROS-level microenvironments. In vivo rat periodontitis treatments further demonstrate their superior anti-ROS therapeutic effects. This study provides significant insights into the crucial functions of Ru-N coordinated porphyrin-networks in catalytic ROS-scavenging and offers a new strategy to engineer high-performance antioxidase-like nanobiocatalysts for stem cell-based therapies and inflammatory diseases.

Periodontitis, one of the most common, challenging, and rapidly expanding oral diseases, is an oxidative stress-related disease caused by excessive reactive oxygen species (ROS) production. Developing ROS-scavenging materials to regulate the periodontium microenvironments is essential for treating periodontitis. Here, we report on creating cobalt oxide-supported Ir (CoO–Ir) as a cascade and ultrafast artificial antioxidase to alleviate local tissue inflammation and bone resorption in periodontitis. It is demonstrated that the Ir nanoclusters are uniformly supported on the CoO lattice, and there is stable chemical coupling and strong charge transfer from Co to Ir sites. Benefiting from its structural advantages, CoO–Ir presents cascade and ultrafast superoxide dismutase-catalase-like catalytic activities. Notably, it displays distinctly increased V max (76.249 mg L–1 min–1) and turnover number (2.736 s–1) when eliminating H2O2, which surpasses most of the by-far-reported artificial enzymes. Consequently, the CoO–Ir not only provides efficient cellular protection from ROS attack but also promotes osteogenetic differentiation in vitro. Furthermore, CoO–Ir can efficiently combat periodontitis by inhibiting inflammation-induced tissue destruction and promoting osteogenic regeneration. We believe that this report will shed meaningful light on creating cascade and ultrafast artificial antioxidases and offer an effective strategy to combat tissue inflammation and osteogenic resorption in oxidative stress-related diseases.