Advanced Healthcare Materials最新文献

Retinal damage remains a leading cause of irreversible vision loss, with conventional surgical and pharmacological approaches limited by suboptimal efficacy and safety concerns. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) demonstrate promise for retinal repair through their low immunogenicity, anti-inflammatory, antioxidant, and neuroprotective properties. These nanovesicles deliver functional proteins and miRNAs that enhance neuronal survival, suppress pathological angiogenesis, and attenuate inflammatory cascades, demonstrating efficacy in models of retinal injury. However, rapid systemic clearance and frequent dosing requirements hinder clinical translation. Hydrogel-based delivery systems address these challenges by improving intraocular retention and bioavailability via biocompatibility, controlled release, and barrier protection. This review critically analyzes current retinal treatments, discusses the mechanisms and translational challenges of MSC-EVs, and evaluates the design principles of hydrogel biomaterials. It also synthesizes progress in hydrogel-EV combination strategies for ocular diseases, highlighting their synergistic therapeutic effects while addressing scalability and biosafety issues. The innovative integration of biomaterial and EV therapeutics advances targeted approaches for retinal regeneration.

3D-printed self-healing hydrogels represent a significant advancement in regenerative medicine. Long-lasting, patient-tailored tissue scaffolds that evolve with native tissues may result. Preventing unwanted biomaterial growth is a major concern. The "Printability-Healing Paradox" is the central challenge, involving a trade-off between rheological properties for high-fidelity 3D printing and dynamic network features for self-healing. Resolving the paradox requires understanding hydrogel bioinks, chemical tools for self-healing (e.g., Schiff base, Diels-Alder, and hydrogen bonding), and rheological requirements for printability (e.g., shear-thinning and yield stress). Our review has explored advanced material design strategies, including multi-network architectures, nanocomposite reinforcement, and orthogonal crosslinking chemistries, to address this issue. Case studies in neuro, musculoskeletal, and cutaneous tissue engineering demonstrated how these methods might improve tissue-specific bio-functionality and alleviate problems. Designing smart materials is crucial for the profession to address the Printability-Healing Paradox. Developing multi-material printing platforms, AI-driven bioink design, and 4D characteristics will enable therapeutic structures that mimic biological organisms and adapt to the body.

Piezoelectric materials generate charges that directly interact with cancerous tissue or stimulate the production of reactive oxygen species (ROS) for innovative tumor therapies mediated by sonography. However, the precise optimization of piezoelectric nanomaterials, combined with overcoming apoptosis resistance, represents a substantial challenge that requires immediate attention. In this study, we have strategically designed cancer cell membrane-coated sodium metaniobate (NaNbO₃; MNO) piezoelectric nanocubes with inherent homologous targeting capabilities and exceptional ROS-generating potential for the treatment of lung cancer. The cell membrane encapsulation technique significantly enhances the accumulation and retention of the nanopiezoelectric system at the tumor site. Crucially, in addition to its apoptotic induction properties, the increased ROS production activates pyroptosis via the ROS-NLRP3-Caspase-1-GSDMD signaling pathway, thereby augmenting therapeutic efficacy against tumors. Both in vitro and in vivo antineoplastic evaluations validate the advantages and potential of this biomimetic nanopiezoelectric system. This study underscores the role of biomimetic sonopiezoelectric engineering in catalytically inducing a dual mode of cell death, involving both apoptosis and pyroptosis, within lung cancer cells.

Mandibular bone defects, especially critical-sized ones, are a major challenge in oral and maxillofacial surgery. Electrical stimulation (ES) enhances bone repair, but its underlying mechanism remains elusive. This study presents a masticatory-driven piezoelectric hydrogel that converts chewing motions into endogenous-like ES, triggering on-demand NPY condensate release to enhance regeneration, validated in rat critical-sized defect models. NPY as a key mediator is identified: ES triggers its phase transition to activate osteogenic signaling. The engineered hydrogel generates >20 mV cm^-1 (exceeding the ≥2 mV cm^-1 threshold for NPY liquid-liquid phase separation, LLPS) under physiological chewing. ES induces NPY conformational rearrangement (N-terminus buried) to activate Y2 receptors (Y2R) on periodontal ligand-derived stromal cells (PDLSCs). Mechanistically, ES plus NPY condensate promotes osteogenic differentiation of PDLSCs through pAKT-Runx2 signaling. In vitro, the hydrogel boosts PDLSCs osteogenesis by 2-fold (p < 0.001). In 4-week and 12-week rat mandibular bone defects, it yielded greater bone volume and higher density (p < 0.01) vs. controls, with Y2R-pAKT-RUNX2 activation confirmed. This self-powered strategy leverages mastication for targeted ES, offering a mechanism-driven solution that addresses current limitations and holds clinical promise.

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) utilize cobalt-chromium-molybdenum alloys; however, the release of cobalt ions is a significant clinical concern. Ceramic-based alternative systems also have concerns regarding long-term mechanical stability. Ti6Al4V (Ti64) is a better alternative; however, it is unsuitable for articulating surfaces due to its low wear resistance. We have designed and manufactured a novel Ti64-based composite by adding 45S5 bioglass (BG) and copper (Cu). Adding BG on titanium improves wear resistance and biocompatibility, whereas Cu addition improves mechanical strength while providing inherent lifelong bacterial resistance. Ti64, Ti64-1 wt% BG (Ti64-1BG), Ti64-3 wt% BG (Ti64-3BG), and Ti64-3 wt.% BG-3 wt.% (Ti64-3BG-3Cu) compositions were processed using the laser-directed energy deposition (L-DED) additive manufacturing (AM) technique. Microstructural characterisation and phase analysis were done to evaluate the influence of BG and Cu addition on Ti64. While BG was preferentially located along the melt pool boundaries, Cu was uniformly distributed throughout the sample. Uniaxial compression tests were conducted, and the addition of BG and Cu increased the strength. Biotribological analysis using flat-on-disc fixtures under fully immersed conditions in DMEM revealed that wear resistance improved due to the addition of BG and Cu to Ti64. Tribological testing revealed the formation of a protective nanoscale tribofilm on BG-containing samples, as indicated by increased contact resistance and reduced wear rates at higher loads. In vitro biocompatibility studies were done with human osteoblast (OB) cells for 3 and 7 days. Cell attachment and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays were performed to understand the influence of BG and Cu on biocompatibility, with Ti64 serving as a control. An antibacterial test was performed for 24 and 72 h using Staphylococcus aureus to evaluate the influence of Cu addition on the sample's antibacterial properties. Overall, the results demonstrated a superior implant material with enhanced biocompatibility, inherent antibacterial properties, and improved wear resistance through the innovative formation of a protective nanoscale tribofilm.

Conventional fluorescence imaging in the visible and first near-infrared (NIR-I, 700-900 nm) windows is limited by tissue scattering and autofluorescence. The second near-infrared (NIR-II, 1000-3000 nm) window offers deeper penetration depth and higher signal-to-noise ratio due to reduced photon scattering. Among the high-performance probes, atomically precise gold clusters emerge as a promising class of materials, as their defined structure can be engineered for enhanced NIR-II emission. Here, we report controllable Au₁₈ clusters for NIR-II bioimaging, which exhibit superior brightness, stability, and biocompatibility. We successfully dope a single Zn atom into the Au₁₈ cluster structure, thereby optimizing optical properties and improving photostability. Zn atom doping shifts the energy levels downward by approximately 1.2 eV and induces local charge redistribution, resulting in enhanced photoluminescence. The Au₁₇Zn₁ clusters exhibit a 4.1-fold NIR-II fluorescence enhancement and high temporal stability with excellent biological safety. Furthermore, Au₁₇Zn₁ shows potential for visualizing liver tissue in mice with hepatic ischemia-reperfusion injury (HIRI). In addition, three-dimensional (3D) imaging of HIRI mice using light-sheet microscopy (LSM) reveals vascular dilation from approximately 120 to 300 µm, clearly delineating the different stages of HIRI. Therefore, Au₁₇Zn₁ shows potential as a tool for HIRI assessment.

Chemoimmunotherapy has emerged as a promising treatment modality for triple-negative breast cancer (TNBC). However, its clinical utility is often hindered by the severe toxicity of chemotherapeutic agents and the immunosuppressive nature of the tumor microenvironment (TME). Herein, we engineer an injectable 5-fluorouracil-constituted DNA hydrogel embedded with quercetin (Q-5FDHG) through a novel DNA amplification reaction to navigate these impediments in a dual-pronged manner. Q-5FDHG ensures progressive enzymatic degradation, which continuously releases 5-fluorouracil (5FU) and quercetin (Que). Que attenuates the secretion of C-C motif chemokine ligand 2 (CCL2), thereby reducing the recruitment of tumor-associated macrophages and remodeling the immunosuppressive TME. Simultaneously, 5FU inhibits tumor cell proliferation with reduced systemic toxicity by optimizing local administration and induces immunogenic cell death (ICD) to enhance tumor immunogenicity. In orthotopic murine models of TNBC, Q-5FDHG exhibits remarkably specific anti-tumor immune responses and boosts anti-tumor efficacy, resulting in significant inhibition of tumor growth and lung metastasis. This study demonstrates a unique chemoimmunotherapy efficacy induced by the chemotherapeutic agent 5FU and small-molecule compound Que from traditional Chinese medicine, and provides a safe and effective therapeutic strategy for TNBC with great promise for clinical translation.

Pressure-sensitive adhesives (PSAs) are core materials for wound care and medical fixation, yet their clinical application is constrained by three key contradictions: high adhesiveness easily causes skin damage during peeling, while low adhesiveness leads to dressing edge lifting and increased infection risk, and traditional PSAs generally lack antibacterial and wound-healing-promoting functions. To address these issues, this study proposes a "function-integrated PSAs" strategy by combining emulsion-polymerized cationic polyacrylate (CPPSA) with tunable adhesion and antibacterial properties and chitosan (CS) for hemostasis and wound regulation. This CPPSA-CS system integrates three core synergistic functions: electrostatically targeting and disrupting bacterial cell membranes for antibacterial protection, optimizing adhesive performance to balance bonding stability and low-damage peeling, and accelerating hemostasis and mitigating inflammatory responses at the wound site to modulate the wound microenvironment. This study overcomes traditional PSAs' limitation of single fixation function through material and functional innovation, providing a new technical approach for multi-dimensional infected wound management with significant clinical translation value.

Diabetic wound infection remains a devastating threat to human health, largely due to bacterial colonization and increased antibiotic resistance during conventional treatments, and alternative therapeutic strategies are thus urgent to improve diabetic wound healing. Herein, we developed a multifaceted nanoplatform (CuO@SiO₂@NO@Au, CSNA NPs) consisting of a cupric oxide (CuO) core, a mesoporous silicon nanoshell loaded with nitric oxide (NO), and in situ grown ultrasmall Au nanoparticles (NPs) for improved diabetic wound treatment. The results showed that the prepared CSNA NPs exhibited remarkable dual-enzyme mimic activity of glucose oxidase (GOx) and peroxidase (POD), effectively oxidizing glucose to generate gluconic acid, thereby reducing the glucose levels and reversing the acidic wound microenvironment. In addition, the fabricated nanoplatform generated abundant H₂O₂, which was converted into highly toxic hydroxyl radical (·OH), leading to efficient bacterial eradication that was subsequently. Under near-infrared (NIR) light irradiation, the CSNA nanozyme also triggered the release of NO gas and aided in the removal of bacterial biofilms, collectively improving the wound microenvironment. By integrating chemodynamic therapy (CDT), photothermal therapy, and NO gas therapy, this self-activatable NIR- augmented nanozyme provides a promising antimicrobial strategy for diabetic wound treatment.

Hafnium oxide (HfO₂)-based nanomaterials are emerging as powerful tools to enhance radiotherapy by utilizing their high atomic number (Z). By depositing a greater radiation dose directly within tumors, they offer a promising route to improve treatment efficacy. This review traces the development of HfO₂ nanoradiosensitizers, starting with the clinically established NBTXR3, an approved hafnium-based benchmark for several solid tumors. We analyze the structural characteristics and radiosensitization mechanisms of nanoscale HfO₂, which include improved X-ray absorption, radical generation, and immunomodulation. Key synthesis methods such as sol-gel, precipitation, and hydrothermal approaches are evaluated in detail, with emphasis on their tunable parameters and reproducibility. Recent progress focuses on material optimization through size control, surface engineering, composite design, and Hf-MOFs, as well as combination strategies. Despite encouraging preclinical results, challenges remain in scalable fabrication, long-term biosafety, and clinical translation. Future directions point toward smart stimuli-responsive platforms and multimodal theranostic systems. This review highlights the potential of HfO₂ to precision radiotherapy while acknowledging existing translational challenges.