Conventional wound dressings have challenges in achieving precise spatiotemporal coordination between antibacterial activity and tissue regeneration, leading to poor infection control and delayed healing. Herein, we report a photothermal-responsive hydrogel for programmed antibacterial and regenerative remodeling with a controllable cascade response. The hydrogel incorporates matrix metalloproteinase (MMP) degradable polyethylene glycol (PEG) cross-linked networks, thermosensitive gelatin, photothermal indocyanine green (ICG), and the antibiotic levofloxacin, allowing for controlled gel-sol transition and sequential therapeutic release upon near-infrared (NIR) irradiation. Once implanted onto infected wounds in normal and diabetic rat models, NIR activation induces local heating of the hydrogel, facilitating dissolution of the gelatin and release of the antibiotic from the hydrogel matrix. Early stage antibacterial activities are achieved by both photothermal sterilization and antibiotic release into the wound site, markedly reducing bacterial viability and further inhibiting biofilm formation. In the subsequent regenerative stage, the released gelatin provides favorable adhesion sites for cells and promotes angiogenesis and tissue remodeling, thereby accelerating wound healing. This platform controllably orchestrates antibacterial and regenerative processes, offering a novel strategy for complex tissue repair.

As three-dimensional biomimetic systems developed from stem cells or somatic cells, organoids have gradually evolved into important links between basic research and clinical application. Compared with traditional two-dimensional culture and animal models, organoids can better reflect the structure and function of tissues and organs in terms of physiological relevance and prediction efficiency. This review explores the integration of organoid technology with microfluidic technology, gene editing, and artificial intelligence, focusing on the prospects of these technologies for application in precision medicine, disease modelling, drug screening, and toxicology. In addition, the latest progress in organoid research, including organ-on-a-chip, organoid biobank construction, and related applications of regenerative medicine, is summarized. The development of key technologies is reviewed in detail. These technologies include improvements in culture systems, innovations in microfluidic and matrix materials, gene editing and modification, and imaging and multiomic analyses. These achievements improve the application value of organoids in disease modelling, drug screening, and toxicology. Despite challenges such as standardization, batch-to-batch consistency, and clinical translation, the integration of interdisciplinary technologies has provided a new impetus for the development of organoids. In the future, the combination of organoids with artificial intelligence, personalized medicine, and regenerative medicine is expected to drive research progress on disease mechanisms and precision treatment.

Exosomal metabolite profiling represents a promising non-invasive approach for cancer diagnosis. However, its widespread application has been constrained by inefficient exosome isolation and cumbersome metabolomic workflows. Herein, we introduce a "magnetic-catcher" composite comprising a spiky TiO2 shell with 3D nano-traps for efficient exosome capture via spatial complementarity and affinity interactions, and a superparamagnetic Fe3O4 core for rapid magnetic separation. Oxygen vacancies and heterointerfaces engineered on the shell enhance light absorption and charge separation, enabling the material to serve as an efficient matrix for laser desorption/ionization mass spectrometry (LDI-MS). During analysis, the particles simultaneously lyse captured exosomes and promote metabolite desorption/ionization, achieving high sensitivity and reproducibility (CV < 15%). Ultimately, an integrated magnetic-catcher/MALDI-MS platform was established, which consolidates exosome isolation and metabolomic analysis into a streamlined workflow. The integrated platform was applied to plasma from pancreatic ductal adenocarcinoma (PDAC) patients, yielding high-quality exosomal metabolic profiles. Machine learning analysis achieved accurate PDAC diagnosis and staging within the study cohort, with area under the curve (AUC) values of 1.000 for both tasks, and potential biomarkers (D-glucose, lysine, 6-methyloctanoic acid, phenyllactic acid, and 3-oxodecanoic acid) were identified. Future studies involving larger, multi‑center cohorts are required to validate the generalizability and clinical utility of our approach.

Antimicrobial resistance (AMR) remains a critical global health challenge, exacerbated by antibiotic misuse that accelerates bacterial tolerance and undermines therapeutic efficacy. The lack of new antibiotics and the high cost of drug development further intensify the urgency for the development of alternative antimicrobial strategies. Emerging evidence suggests that biomaterials can disrupt the progression from antimicrobial tolerance (AMT) to AMR, offering a promising avenue to enhance treatment outcomes and suppress the rise of resistant strains. This review outlines the transition mechanisms from bacterial tolerance to resistance and explores how biomaterials can counter these adaptations. Using properties such as electrostatic interactions, ligand coordination, and vesicular disruption, biomaterials can inhibit bacterial growth and alter the metabolism, preventing AMT-to-AMR progression. They also initiate programmed cell death pathways and generate oxidative stress through photothermal, photodynamic, and chemodynamic therapies, and can also target bacterial DNA and protein synthesis. Additionally, biomaterials enhance immune responses including neutrophil activity and macrophage polarisation. Using biofilm and intracellular infection models, we show that biomaterials effectively prevent biofilm formation and target intracellular pathogens. Finally, we summarize infection mechanisms in organoid-based models, including immune and bacteria-organoid systems. In summary, this review highlights biomaterials as versatile agents with outstanding potential for future antimicrobial strategies.

Osteoarthritis (OA) is predominantly driven by chondrocyte senescence, accompanied by progressive cartilage degradation. Facing the substantial worldwide impact of this condition, creating sustainable and economical therapies has become increasingly urgent. Plant-derived extracellular vesicles (PEVs) present a highly attractive option, notably because they are readily sourced, exhibit minimal immunogenicity, boast excellent biocompatibility, and can be produced at scale. Crucially, these nanovesicles facilitate cell-to-cell signaling by shuttling inherent bioactive cargo. In our study, we propose to utilize grape skin-derived extracellular vesicles (GSEVs), a by-product of the food industry, as a new nanotherapeutic platform. By coupling GSEVs with a type II collagen-binding peptide (WYRGRL), we generated cartilage-tendency-enhancing W-GSEVs that increased their accumulation and retention time in articular chondrocytes. In vitro findings demonstrated that W-GSEVs attenuated chondrocyte senescence by reducing reactive oxygen species (ROS) production and inhibiting both IL-17 and TNF signaling pathways. In vivo experiments further demonstrated that intra-articular injection of W-GSEVs effectively mitigates chondrocyte senescence in OA mice, thereby protecting cartilage from breakdown, reducing abnormal bone growth, and normalizing subchondral bone remodeling. This treatment notably slowed OA advancement and helped maintain balanced matrix metabolism. This work not only repurposes agricultural waste into a high-value biomedical tool, but also highlights the clinical translational potential of PEVs as a scalable, low-immunogenic platform for OA treatment by directly targeting chondrocyte senescence.

The mechanism of tendon-bone healing is highly complex and multifaceted, being influenced by a wide range of factors that can determine the healing outcome. In the past two decades, a variety of therapeutic approaches have been explored and refined to enhance tendon-bone healing. Organoid culture technology, which has emerged as a cutting-edge research tool, involves the creation of three-dimensional tissues that can self-renew and self-organize, closely mimicking the spatial characteristics of natural biological structures. Integrating existing therapeutic strategies into the development of tendon-bone junction organoids offers a highly promising approach for accurately simulating the tendon-bone junction. Therefore, this review first clarifies the anatomical structure of the tendon-bone junction and the detailed process of tendon-bone healing. Then, the latest application of treatment strategies aimed at promoting tendon-bone healing is highlighted. These approaches include cell-based therapies, cell-derived approaches, biomimetic scaffolds, and external stimulations. This review provides a comprehensive overview and discusses potential applications and future challenges of biomaterials in the development of tendon-bone junction organoids. With the continuous advancement of organoid technology, these therapeutic strategies are expected to emerge as powerful tools for enhancing tendon-bone healing. Statement of Significance Despite extensive exploration of various therapeutic strategies, the clinical outcomes of tendon-bone healing remain suboptimal and unpredictable. This is largely due to the highly complex and multifaceted nature of the healing process, which existing experimental models fail to fully recapitulate. Therefore, a robust platform is needed to model the native tendon-bone junction and evaluate combination therapies. Tendon-bone junction organoids have emerged as a highly promising approach to meet these requirements. A comprehensive review that systematically bridges the gap between established therapeutic strategies and this innovative organoid technology is currently lacking. This review aims to fulfill this critical need by synthesizing the current knowledge on tendon-bone anatomy, healing mechanisms, and cutting-edge therapies to guide the rational development of biomaterial-enhanced organoids. By providing a foundational framework, this review is expected to accelerate the advancement of more effective and personalized strategies for enhancing tendon-bone repair, ultimately improving the prognosis for countless patients with related injuries.

Articular cartilage defects are inherently difficult to treat given the tissue’s avascularity and minimal intrinsic regenerative capacity. Although stem cell-derived organoids offer promise for cartilage regeneration, insufficient dimensional scalability and poor host-tissue integration remain key limitations. Here, we developed a 3D-bioprinted piezoelectric cartilage-bone integrated organoid system using two functionally distinct bioinks: a chondrogenic matrix of methacrylated chondroitin sulfate (ChSMA), barium titanate (BTO) nanoparticles, and TGF-β and an osteogenic matrix of gelatin methacrylate (GelMA), BTO, and nano-hydroxyapatite (nHA). This bilayer design establishes compartment-specific microenvironments that guide bone marrow mesenchymal stem cell (BMSC) differentiation toward chondral and osseous lineages while maintaining spatial segregation between the two compartments. Incorporated BTO nanoparticles convert mechanical stimulation into localized bioelectrical cues, enhancing cellular responsiveness and tissue maturation. The biomimetic osseous layer provides structural anchorage at the defect site. Our results demonstrate stratified extracellular matrix formation with compartment-specific compositions, offering a mechanistically grounded approach for osteochondral defect repair.

ABSTRACT Bone injuries, particularly those associated with an aging global population, pose a persistent and complex clinical challenge. Current gold‐standard treatments such as autografts, allografts, and metal implants, are often limited by immune rejection and mechanical mismatch. In this context, hydrogels are promising biomaterials for bone regeneration, due not only to inherent biocompatibility, high hydration, and tunable elasticity but also to the ability to mimic the native bone micro environment. This review presents a critical and comprehensive analysis of how hydrogels for bone repair are designed, constructed, and functionalized to achieve the desired regenerative performance. It systematically examines multiple hydrogel types, centering on the design of their strength and biodegradation features to better align with the functional demands of bone healing. Furthermore, the review summarizes that by incorporating bioactive molecules, nanomaterials, or cells, advanced functionalization can orchestrate osteogenesis and angiogenesis. In vitro and in vivo studies evidenced the performance of hydrogels' applications ranging from bone fracture repair to smart, stimuli‐responsive platforms for personalized regenerative medicine. This review finally identifies the prevailing translational challenges and suggests future research trajectories.

Global population aging has made skeletal disorders a major threat to human health. Solid bone organoids reproduce skeletal physiology and pathology more faithfully than traditional models, yet remain limited in standardisation, real-time monitoring, and high-throughput use. Integrating artificial intelligence (AI) with computational biology offers a route to ease these limits and motivates an emerging direction we develop here. We use virtual bone organoids (VBOs) for the in silico counterpart of a solid bone organoid, and artificial intelligence virtual bone organoids (AIVBOs) for its AI-driven realisation, which takes the virtual cell as its basic unit and fuses multimodal omics data with biophysical constraints. It remains an early-stage proposal, since most capabilities discussed here have been shown only in non-bone systems such as virtual cells and AI-assisted organoids and are carried over to bone rather than established in it. This review traces the logic from solid bone organoids to the AIVBO as a meso-scale digital-twin approach. We outline a modular strategy across stem-cell differentiation, vascular and immune coupling, and pathological evolution, and consider the prospective value of AIVBOs for standardised organoid construction, reverse design of biomaterials, mechanistic analysis, reagent-sparing drug screening, and in silico trials. Throughout, we separate goals already supported by real data from longer-term aspirations and address the main limitations directly, including data noise, bias, and sparsity, organoid irreproducibility, limited digital-twin fidelity, interpretability, data fusion, and ethical and regulatory issues. As a digital bridge between microscopic mechanism and macroscopic phenotype, AIVBOs may help move bone research from descriptive experimentation toward predictive engineering, though substantial experimental validation remains a prerequisite for clinical translation. The translational potential of this article AIVBOs are framed as a meso-scale digital-twin concept meant to complement, not replace, solid bone organoids and in vivo models. Their translational potential lies in using calibrated in silico models to narrow the experimental search space for biomaterial design, drug screening, and disease modelling, which could cut the cost and time of pre-clinical orthopaedic research and support more standardised, predictive, and personalised care for bone repair and metabolic bone disease. These benefits are prospective and contingent on rigorous validation, transparent reporting of model limits, and shared data and quality standards.

The emergence and development of artificial intelligence is rapidly promoting dental diagnosis and treatment from experience-driven to data-driven and accurate methods. With the help of AI models based on deep learning, AI has been widely used in dental fields such as oral radiology, orthodontics and maxillofacial surgery, periodontal disease and dental pulp, aesthetic restoration and so on. In addition, AI technology has also made great contributions in forensic dentistry and tele dentistry. The application of a technology can not only improve the limitations of traditional treatment methods, but also improve the accuracy of treatment of dental caries, periapical lesions, and other diseases. However, its clinical promotion is still limited by data imbalance and heterogeneity, privacy and security, lack of model interpretability and lack of standardized evaluation system. In the future, it is urgent to build high-quality multicenter data sets, introduce privacy computing technologies such as federal learning, and improve regulatory and human-computer collaboration specifications, so as to realize the safe and controllable application of AI in dentistry, and promote the overall transformation of oral medicine to prevention oriented, precision diagnosis and intelligent services.

The repair of large cranial defects remains a major clinical challenge, as conventional materials primarily act as inert fillers and fail to meet the complex biological requirements of cranial bone regeneration. In particular, they lack the ability to temporally coordinate angiogenesis and osteogenesis. This study aimed to develop a temporally functional composite scaffold to dynamically modulate the regenerative microenvironment and promote sequential vascularized bone regeneration. Methods: A silk fibroin-based hydrogel system was designed, incorporating salvianolic acid B (SalB)-loaded sustained-release hydrogel and mineralized silk fibroin hydrogel microspheres (MSFM). Material characterization was performed to evaluate the structural and mechanical properties of the scaffold, as well as the drug release behavior. In vitro assays were conducted to assess endothelial cell migration, tube formation, and the expression of angiogenesis-related genes, along with the osteogenic differentiation potential of bone marrow-derived mesenchymal stem cells (BMSCs). In vivo reparative efficacy was further validated using a rat cranial defect model through morphological and histological analyses. Results: Characterization confirmed that OSFM microgels were uniformly spherical with a porous internal structure and exhibited sustained release of OGP. In vitro, OSFM showed excellent cytocompatibility with BMSCs, significantly enhancing cell proliferation, ALP activity, and mineralized nodule formation compared with SFM (p < 0.05). Tube formation and scratch assays demonstrated that OSFM-conditioned medium promoted HUVEC migration and angiogenesis. In vivo, implantation of OSFM+PCL scaffolds into rat calvarial defects resulted in markedly superior bone regeneration compared with control, PCL, and SFM+PCL groups. The bone volume fraction in the OSFM+PCL group reached 52.31 ± 4.27% at the 8th weeks, significantly higher than 23.65 ± 3.81%, 30.42 ± 3.96%, and 37.86 ± 4.12% in the other groups (p < 0.05). Histological staining confirmed more mature bone formation, abundant collagen deposition, and tight integration between new bone and scaffold. Immunohistochemistry revealed upregulated expression of RUNX2, OCN, and CD31, indicating enhanced osteogenesis and angiogenesis. Conclusions: This temporally functional composite scaffold achieved a sequential "angiogenesis first, osteogenesis later" strategy by leveraging the differential degradation kinetics of its components. The findings demonstrate a biomimetic and temporally regulated approach with strong bioactivity and translational potential for cranial bone regeneration.

Chronic cutaneous wounds such as diabetic foot and pressure ulcers are increasing worldwide and remain difficult to manage. Conventional approaches are hindered by prolonged healing and antibiotic resistance, highlighting the need for advanced biomaterial strategies. Thus, the production of advanced biomaterials for efficient wound healing has become of special urgency. Mesoporous silica (MS), with its specific features of exceptional biocompatibility, easily tunable pore architectures, and multifunctional surface functionalization, has emerged as a promising choice in such applications. The review systematically overviews the most recent advances in the wound healing application of MS, with its participation in drug delivery, controlled inflammation, modulation of immune response, tissue regeneration, and angiogenesis. Synthesis methods, surface functionalization techniques, and incorporation of advanced technology such as stimulus responsive systems and multifunctional composites are also extensively reviewed. Furthermore, this review critically examines the key barriers to the clinical translation of MS, including long-term biosafety, immune compatibility, and scalable manufacturing. Overcoming these challenges is crucial for harnessing its full potential in next-generation wound healing. By integrating MS with precision medicine and emerging biomedical technologies, this review highlights its transformative role in advancing personalized wound care and regenerative medicine. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Reversing extracellular matrix (ECM) metabolic dysregulation to facilitate cartilage repair represents a key therapeutic strategy for osteoarthritis (OA) treatment. Owing to the avascular nature of joint structures, intra-articular injection is a commonly used clinical administration route. However, the current drug retention time is insufficient to effectively reverse OA progression. In this study, we demonstrated that natural bacterial extracellular vesicles (BEVs) are capable of repairing cartilage damage. We modified Lactobacillus rhamnosus GG (LGG)-derived BEVs with a chondrocyte-targeting peptide to prolong their therapeutic efficacy. Engineered BEVs, as a drug delivery system, are capable of continuously transporting endogenous miRNAs. Cartilage-targeting LGG-EVs (W-LGG-EVs) penetrate deeply into cartilage tissue and promote extracellular matrix secretion by chondrocytes. Furthermore, W-LGG-EVs were shown to restore cartilage homeostasis and ultimately alleviate stress-related OA. BEVs, as a novel and safe therapeutic agent, hold clinical feasibility.

Organoid-based strategies offer unique advantages for bone regeneration by recapitulating the multicellular architecture and dynamic microenvironment of native tissue. However, their clinical translation remains constrained by reliance on immunogenic, animal-derived matrices and limited immunomodulatory capacity. We propose a non-immunogenic, xeno-free, and cytokine-free plant-derived bioink composed of aloe vera gel, laponite nanoclay, and gelatin methacrylate (GelMA) for constructing immune-instructive bone organoids. This bioink enables long-term reprogramming of macrophages toward an M2 phenotype without exogenous cytokines, establishing a stable pro-regenerative immune microenvironment that enhances mesenchymal stem cell osteogenesis and extracellular matrix (ECM) maturation. The construct supports robust 3D tissue organization, immune-guided osteoinduction, and functional integration in vivo. Notably, this is the first demonstration of a plant-based bioink platform for organoid bioengineering, offering a scalable and translationally viable

The misuse of antibiotics has accelerated bacterial resistance, with methicillin-resistant Staphylococcus aureus (MRSA) posing a major global threat. Regulating bacterial metabolic pathways is a promising strategy, particularly pigment biosynthesis. Here, we engineered a hybrid hydrogel (Van@PCMOF@T/H) by embedding thymol and covalently anchoring a copper-phthalocyanine metal-organic framework (MOF) loaded with vancomycin (Van@PCMOF) within a methacrylated hyaluronic acid matrix. In a vancomycin-tolerant MRSA model (MRSAtol), thymol effectively suppresses staphyloxanthin (STX) biosynthesis, thereby restoring bacterial susceptibility to vancomycin and oxidative stress. Upon near-infrared (NIR) activation, the system produces heat and reactive oxygen species and releases vancomycin together with copper ions, synergistically triggering cuproptosis, DNA damage, membrane destabilization, and biofilm disruption. In a murine skin-infection model, NIR-triggered treatment accelerates bacterial clearance, reduces inflammatory responses, and promotes wound healing. This metabolism-reprogramming platform provides an effective strategy to restore antimicrobial efficacy against antibiotic-tolerant bacterial infections.

Damage of hard tissue like bones and teeth has become an increasingly serious global problem in clinic. In-situ biomimetic mineralization strategy plays an indispensable role in hard tissue repair due to its advantages of imitating the mineralization process in vivo. Central to this process is the role of organic matrices in guiding the orderly arrangement of functional motifs at the nanoscale. Herein, this review focuses on the types of organic matrices and their regulatory effects on the in-situ assembly of hydroxyapatite-based functional motifs, emphasizing underlying mineralization mechanisms. Key mechanisms and pathways through which organic matrices control the oriented arrangement of functional motifs are discussed, along with strategies to enhance matrix-guided mineralization. Furthermore, various methods and applications of in-situ mineralization for hard tissue regeneration are comprehensively summarized. Finally, current challenges and future opportunities are presented, highlighting the potential of advanced technologies such as artificial intelligence and organoids in elucidating mechanisms and advancing applications of in-situ mineralization. It is hoped that this review will provide reference value for the design principles and development of hard tissue repair materials in the future.