Abstract Stiffness is a key mechanical cue of the extracellular matrix (ECM) and biomaterials in tissue engineering. It plays a pivotal role in regulating cellular behaviors and determining cell fate through specific mechanotransduction pathways, including integrin‐mediated signaling and cytoskeletal dynamics. Biomaterials with tunable stiffness in both two‐dimensional (2D) and three‐dimensional (3D) formats have been developed to investigate the influence of stiffness on tissue regeneration. This is particularly relevant in the motor system, where tissue stiffness spans a broad range and mechanical cues are crucial. In this review, we first highlight the multiple roles of matrix stiffness in biological processes, from guiding tissue development and maintaining homeostasis to regulating cell behaviors. We then summarize the design and fabrication strategies for tunable‐stiffness biomaterials in both 2D and 3D formats. Finally, we discuss the functional applications of these biomaterials in the motor system and their potential applications in regenerative medicine.
Abstract Extracellular vesicles (EVs) are double‐membrane vesicular structures that can be secreted by nearly all living cells. These vesicles serve as “carriers” enabling the intercellular transport of membrane‐bound and soluble proteins, lipids, and RNA. Hence, EVs mediate the transfer of bioactive substances between different cells, playing a crucial role in intercellular communication. In particular, plant‐derived EVs (P‐EVs) have garnered significant attention in recent years due to their wide availability, excellent biocompatibility, inherent stability, low immunogenicity, and non‐toxicity. The potential of P‐EVs as natural therapeutic agents and drug delivery vehicles has been increasingly recognized, offering promising therapeutic avenues for various diseases. In this article, we first discuss the nomenclature of P‐EVs. We then review current strategies for their isolation and characterization as well as properties and biosafety profiles. Given the unique morphology and rich content of bioactive molecules present in these natural nanocarriers, we also summarize recent advances in the engineering and functional modification of P‐EVs, their application as delivery vehicles, and their therapeutic effects in disease models. Furthermore, we review the latest developments in patents and clinical research related to P‐EVs. Finally, we highlight the current limitations and challenges hindering the clinical translation of P‐EVs, including the need for improved isolation and purification methods, comprehensive physicochemical assessments, stringent quality control, safety assessments, delivery route optimization, and in‐depth pharmacodynamic and mechanistic analyses. We hope that this review will provide reference points and guidance for researchers in this field, thereby promoting further advances in P‐EVs research.
Abstract Age‐related bone disorders, such as osteoporosis (OP) and osteoarthritis (OA), are commonly associated with bone loss, cartilage degeneration, and impaired joint function, creating a significant health burden. Bone and cartilage organoids have become promising 3D models because they can partially reproduce natural tissue structures, cell diversity, and extracellular matrix features. However, current organoid systems still rely on biomaterial scaffolds and growth factors, which limits their ability to model multicellular crosstalk. Bacterial extracellular vesicles (BEVs) are non‐replicative nanoscale vesicles released by bacteria and enriched with diverse bioactive molecules. Compared with mammalian EVs or recombinant growth factors, BEVs are attractive because they are genetically programmable, scalable, and low cost. In this review, we discuss how BEVs can be integrated with bone and cartilage organoids, focusing particularly on the biological mechanisms, engineering methods, translational applications, biosafety issues, standardization requirements, and delivery challenges of BEVs. BEVs‐enabled organoids may provide programmable and scalable platforms for skeletal disease modeling, patient‐specific drug screening, and regenerative therapy.
Abstract Inflammatory bowel disease (IBD) complicated by Salmonella infection features a coupled inflammation‐infection pathology driven by oxidative/nitrosative stress, barrier disruption, and microbiome imbalance. Here we report defect‐engineered tungsten oxide (WO 3 ) nanowires as a multifunctional nanozyme platform that integrates redox regulation, pathogen metabolic suppression, and mucosal repair. Defect programming generates abundant oxygen vacancies together with mixed‐valence W 4+ /W 5+ /W 6+ sites, which markedly enhances the catalytic scavenging of reactive oxygen and nitrogen species (reactive oxygen species/reactive nitrogen species) and enables effective control of intestinal redox stress. In parallel, WO 4 2− released from the nanowires competitively interfere with molybdate‐dependent nitrate reductase activity in Salmonella , thereby impairing nitrate respiration and ATP production to attenuate pathogen fitness. In vitro, the defect‐engineered WO 3 nanozymes protect intestinal epithelial cells from oxidative injury and inhibit Salmonella growth. In a DSS‐induced colitis model with Salmonella co‐infection, oral administration significantly alleviated inflammation, restored epithelial integrity, and rebalanced immune and microbial homeostasis. These results establish a defect‐guided redox‐metabolic therapeutic paradigm for addressing inflammation–infection interplay in the gut, and highlight defect‐engineered WO 3 nanowires as a promising chemical platform for complex intestinal disorders.
Abstract Chronic skin wounds remain difficult to treat because infection, oxidative stress, vascular insufficiency, matrix dysfunction, and persistent inflammation reinforce one another and trap repair in a nonhealing state. Tannic acid and bioactive metal ions are increasingly combined to address this problem, yet the literature is often fragmented between TA‐centered formulations, free‐ion strategies, and multifunctional TA–metal assemblies. This review examines these three therapeutic logics in parallel and asks not only what each platform can do but also what wound bottleneck it is actually designed to solve. The discussion first clarifies what TA alone has contributed before TA–metal systems emerged, then evaluates the biological power and formulation risk of free metal ions, and finally analyzes how coordination chemistry enables retention, controlled ion presentation, redox balance, adhesion, and microenvironmental modulation in TA–metal biomaterials. Representative studies are re‐read through wound problems, material format, evidence depth, and translational meaning rather than as a simple catalog of positive outcomes. Particular attention is given to immune microenvironment remodeling, macrophage‐centered claims, stage‐adaptive design, and the distinction between established evidence and attractive but still inferential mechanistic narratives. By integrating material design logic with biological interpretation and translational criteria, this review provides a practical framework for selecting, evaluating, and advancing TA–metal biomaterials for skin repair.
