Advanced Healthcare Materials最新文献

To synergistically enhance the strength-ductility trade‑off and achieve uniform degradation in Fe-Zn alloys, heterostructured alloy microtubes were fabricated via layer‑by‑layer electrodeposition on a rotating soluble aluminum mandrel. Microstructural characterization revealed a columnar‑layered architecture with coherent interfacial bonding after annealing, free of delamination or defects. The heterostructured sample containing ten alternating soft layers (FZ10) exhibited an ultimate tensile strength of approximately 605 MPa and an elongation of about 17.3%, both superior to those of the single-layer alloy. The loading-unloading-reloading (LUR) experiments demonstrated pronounced hetero-deformation induced (HDI) strengthening and HDI strain-hardening effects, indicating the critical role of interfacial constraints in deformation coordination. Electrochemical and simulated body fluid (SBF) immersion tests showed that the heterostructure promoted faster and more uniform corrosion, with an average degradation rate of approximately 0.135 mm·y^{- 1} after 56 days, suppressing localized pitting. XPS and FTIR analyses identified the corrosion products as Fe/Zn oxides and Ca-P compounds, forming a bilayer degradation film with a dense inner layer and a loose outer layer. Additionally, heterostructured Fe-Zn alloy microtubes exhibited favorable cytocompatibility. These heterostructured microtubes integrate high strength, ductility, and controlled and uniform degradability, making them promising candidates for further development as biodegradable vascular stent materials.

Despite considerable progress in cancer immunotherapy, the therapeutic efficacy of current cancer therapy continues to be hampered by the immunosuppressive tumor microenvironment (ITME), which is characterized by acidification, hypoxia, elevated H₂O₂ levels, and aberrant angiogenesis. While transition metal-based nanomaterials hold great promise for modulating the ITME, their effectiveness is often constrained by insufficient reactive oxygen species (ROS) generation, low immunogenicity, poor immune cell infiltration, and T-cell exhaustion. To address these issues, we developed a bimetallic Cu/Mn-doped nanoplatform, CMPTL, which further integrates acid-dissociable taurine and the angiogenesis inhibitor lenvatinib for malignant solid tumor therapy. This nanoplatform simultaneously triggers violent ROS and cuproptosis, leading to mitochondrial damage and the release of mitochondrial DNA. The subsequent activation of the cGAS-STING pathway, synergistically enhanced by Mn²⁺, initiates robust immune responses. Additionally, taurine helps alleviate T-cell exhaustion, while lenvatinib promotes tumor vessel normalization, leading to comprehensive remodeling of the TIME. Together, these multimodal mechanisms endow CMPTL with potent antitumor activity, positioning it as a promising candidate for cancer therapy.

Electrical stimulation (ES) is widely acknowledged as an efficient means for enhancing bone repair. Despite the promising results of synergistic techniques that integrate conductive nanomaterials and ES in excitable tissues, their utilization in bone defect repair is yet inadequately investigated, given the inherent bioelectrical characteristics of bone tissue. In this work, a new osteogenic polyvinyl alcohol (PVA)/pectin/MXene (Ti₃C₂T_x) (PPM) conductive composite hydrogel membrane is designed and comprehensively assessed for its efficacy in electrically enhanced bone regeneration. The PPM membrane with a durable threedimensional (3D) conductive network is formed by combining mechanically resilient, biocompatible PVA and bioactive pectin with highly conductive MXene nanosheets. PVA ensures mechanical integrity and structural stability, pectin with many functional groups promotes cell adhesion and osteogenic bioactivity, while the integration of MXene significantly enhances electrical conductivity, promoting cellular electrical signal transmission and modulating osteogenic cell activities. The PPM membrane has advantageous electrical, mechanical characteristics, and excellent in vitro cytocompatibility and improved osteogenic potential. In vivo experiments indicate that the PPM membrane markedly enhances new bone growth when subjected to ES. This study presents a synergistic approach utilizing a conductive hydrogel membrane and ES, providing a viable biomaterial platform for the repair of bone defects.

Thrombosis and embolism remain leading causes of death worldwide, driven by blood clots that obstruct vascular flow. Current treatments rely on intravenous injections of tissue plasminogen activator (tPA) to dissolve clots, however, free tPA has severe limitations, including poor targeting, and risks of bleeding and hemorrhage. In this work, we look to overcome these limitations with targeted, biodegradable, and hemocompatible glycogen nanoparticles. We develop glycogen-heparin hybrids for complexation with tPA, along with peptide-based targeting towards activated platelets. Our strategy involves leveraging the inherent hemocompatibility of glycogen, with minimal synthetic modifications for targeted delivery of tPA to blood clots. In human blood, the glycogen hybrids have minimal interaction with immune cells, and did not trigger inflammatory or coagulation responses at therapeutic concentrations. Furthermore, they remain biodegradable towards glucosidases inherently in the human body. This design enables thrombus targeting and localized tPA delivery, thereby improving fibrinolytic efficiency relative to free tPA, with steady breakdown kinetics. This was also observed for blood clots subjected to thrombolysis under vascular flow-like conditions. Overall, our approach offers a promising treatment strategy for thrombosis, which improves the therapeutic efficacy of tPA, whilst maintaining excellent hemocomptability.

Electrical stimulation (ES) offers a robust approach to boost the efficacy of stem cell transplantation therapy for the treatment of neurological disorders. Notably, wireless technology blends convenience with the elimination of infection risk posed by wired connections, but the challenge lies in the integration of wireless-enabled stimulation materials and stem cell carriers. Here, we describe a flexible annular conductive dopamine-modified hyaluronic acid (HAD)/polyvinyl alcohol (PVA)/carbon nanotube‌ (CNT) hydrogel that acts as a secondary coil to realize wireless ES via electromagnetic induction, while also serving as a three-dimensional (3D) scaffold carrier for endogenous neural stem cells (NSCs). Established on the annular HAD/PVA/CNT hydrogel with high conductivity and good biocompatibility, wireless ES significantly enhances neuronal differentiation of NSCs. Furthermore, transplantation of the NSC-laden annular hydrogel into a traumatic brain injury (TBI) rat model modulates the behaviors of both exogenous and endogenous neural cells. The combined therapy of wireless ES and NSC transplantation promotes neuronal differentiation in both the injury zone and hippocampus in association with the PI3K-Akt pathway, reduces post-traumatic inflammatory responses, and effectively restores motor and memory functions in TBI rats. This study offers a promising therapeutic strategy of integrating wireless ES with stem cell transplantation therapy for brain injury repair.

Xyloglucan, an immunomodulatory hemicellulose, shows potential for promoting chronic wound healing. However, tunable hydrogels composed solely of xyloglucan with a defined anti-inflammatory mechanism remain elusive. To address this, we developed a single-component, inherently bioactive oxidized xyloglucan (OXG) hydrogel that integrates anti-inflammatory functionality with extracellular matrix (ECM)-mimetic properties. The hydrogel forms autonomously via dynamic hemiacetal crosslinking between aldehyde and hydroxyl groups on the OXG backbone, eliminating the need for exogenous crosslinkers or drug loading. This strategy enables OXG to function both as an immunomodulator and as a supportive scaffold, exhibiting tissue adhesion, injectability, self-healing, and stability in physiological environments. In vitro and in vivo results demonstrated that the OXG hydrogel promotes M2 macrophage polarization and suppresses pro-inflammatory responses by activating the cAMP-PKA signaling pathway, leading to a metabolic shift and inflammation resolution without exogenous cytokines. These actions collectively accelerated diabetic wound closure, enhanced angiogenesis, and facilitated orderly tissue regeneration. This work established a drug-free hydrogel dressing with a well-defined anti-inflammatory mechanism by leveraging the inherent biological activity and self-gelling capability of a single polysaccharide, achieving active remodeling of the immune environment in chronic diabetic wounds. These findings position OXG as a promising natural anti-inflammatory biomaterial for tissue engineering and therapeutics.

Metastatic dissemination is the leading cause of cancer-related mortality, yet the early steps in this process remain difficult to study using current experimental models. Although organ-on-a-chip platforms recapitulate key features of the tumor microenvironment (TME), most fail to integrate physiologically relevant invasion, intravasation, and circulation within a single system. Membrane- and pillar-based designs hinder endothelial crossing and imaging, while open-interface approaches often lack stable perfusion and controlled positioning of 3D cell aggregates. Here, an open-port, barrier-free microfluidic device is presented, fabricated via surface treatment-based patterning, for investigating early metastatic progression from a tumor spheroid. The planar device incorporates a centrally confined gel matrix accessible via a top-loading port for precise spheroid placement, flanked by endothelialized lateral channels in direct contact with the matrix and perfusable under defined shear stress. Using MDA-MB-231 breast cancer spheroids, the model recapitulates key aspects of tumor cell migration, tumor-induced endothelial disruption, and intravasation, while enabling flow-mediated downstream recovery of viable intravasated cells. Overall, this device provides a physiologically relevant platform for the integrated, high-resolution, and longitudinal investigation of early metastatic events, providing a foundation for future mechanistic studies and molecular characterization of metastatic cell populations.

Bone organoids are emerging as three-dimensional skeletal models that reproduce selected aspects of bone development, organization, and function under controlled conditions. Physiologically relevant models require more than cellular aggregation and mineral deposition; they must progressively acquire organized matrices, multicellular interactions, vascular and metabolic support, and mechanical responsiveness. In this review, we examine developmental principles guiding bone-organoid construction, including skeletal hierarchy, cellular niches, ossification pathways, and spatiotemporal signaling. We then discuss current strategies based on skeletal, mesenchymal stromal, and pluripotent stem cells, together with advances in biomaterials, three-dimensional bioprinting, perfusion, and microfluidic culture. To organize these developments, we introduce the development-to-remodeling continuum (DRC), which distinguishes tissue formation from multicellular integration, adaptive responsiveness, and remodeling competence. We assess collagen-mineral organization, osteocyte-network formation, vascular and metabolic maturation, osteoblast-osteoclast coupling, marrow and immune integration, and mechanical adaptation. We further evaluate applications in developmental and disease modeling, drug assessment, personalized modeling, and bone regeneration. Current limitations include variability, incomplete maturation, transport constraints, and insufficient functional benchmarking. By linking construction strategies to specific bone-related functions and the evidence supporting them, the DRC provides a framework for evaluating functional claims in relation to intended application and translational readiness.

The convergence of synthetic biology, materials science, and artificial intelligence drives a transformative shift in biopharmaceutical research, advancing from passive drug carriers to intelligent, programmable therapeutics. This review evaluates artificial and biomimetic cells as a framework that connects fundamental biological discovery with clinical translation. It examines five key technological pathways: membrane-engineered artificial cells, membraneless organelle (MLO) systems, multicompartmental artificial cells, protocell communication networks, and virtual cells. These platforms enable precise regulation of drug stability, targeting, biosynthesis, and adaptive responsiveness. Recent progress includes microenvironment-triggered release, logic-gated intercellular communication, and virtual cell-assisted high-throughput screening and toxicity prediction. Despite these advances, challenges remain in scalable manufacturing, long-term stability, and regulatory adaptation. The integration of closed-loop learning, interpretable models, and advanced biomanufacturing will be essential to position artificial and biomimetic cell systems at the forefront of next-generation precision medicine.