Advanced Healthcare Materials最新文献

Excessive and continuous production of reactive oxygen species (ROS) is a significant factor contributing to severe inflammation, bacterial infections, and poor angiogenesis, and it can also delay the healing of diabetic wounds. However, traditional clinical treatment methods are unable to effectively eliminate ROS. Herein, a dual ROS-scavenging platform that integrates multifunctional niobium carbide (Nb₂C) reinforced with curcumin (Cur) with UV-crosslinked hydrogel microneedles (MN) is presented. In this system, Cur, acting as the primary scavenger, can rapidly neutralize extracellular ROS. Under near-infrared (NIR) irradiation, the embedded Nb₂C not only triggers the on-demand release of curcumin but also, through its enzyme-like peroxidase-mimicking activity, acts as a secondary scavenger to eliminate deep intracellular ROS, thus providing a two-stage antioxidant defense mechanism. This NIR-enhanced dual-action synergistic effect can balance the oxidative microenvironment, promote the repolarization of macrophages from the M1 type to the M2 type, facilitate angiogenesis, and produce a powerful photothermal combined antibacterial effect. The results of in vivo experiments indicate that the use of Nb₂C-CurCD-GelMA MNs can significantly accelerate the healing of full-thickness diabetic wounds. The mechanism lies in coordinating the reduction of inflammation and tissue regeneration. This study offers a sophisticated and safe treatment strategy for refractory diabetic wounds.

Diabetic wound healing is substantially impaired by biofilm infections, oxidative stress, and persistent hypoxia, which present major challenges for timely diagnosis and treatment. In this study, theranostic nanoparticles (NPs) were engineered to facilitate lipase-triggered biofilm theranostics and accelerate wound healing. Theranostic Mn-TC NPs were prepared by grafting a fluorescent sonosensitizer, meso-tetra (4-carboxyphenyl) porphine (TCPP), onto manganese dioxide (MnO₂) nanoflowers, quenching the fluorescence emissions of TCPP. Upon encountering biofilms in vivo, the elevated lipase hydrolyzes ester linkages within the Mn-TC NPs, liberating TCPP to restore its fluorescence emission and enabling the real-time visualization of biofilm-infected wounds. MnO₂ nanoflowers offer abundant reaction sites for TCPP grafting while enhancing the catalysis of hydrogen peroxide to generate oxygen. The boosted oxygen evolution promoted the sonodynamic therapy effect of ultrasound-activated TCPP, achieving 94.0% reduction in biofilm biomass and 99.9% bacterial clearance. Engineering NPs accelerate wound healing by simultaneously eradicating biofilms, modulating inflammatory states, enhancing collagen deposition, and promoting angiogenesis. This study presents a novel theranostic strategy for biofilm-triggered visual imaging and an antibiotic-free therapy for diabetic wounds.

Hydrogels have emerged as one of the most versatile materials with fascinating applications in sensing, soft robotics, energy storage, and biomedicine. To match the pace of rapid advancement, the development of intelligent hydrogels that are able to sense, respond to, and adapt exactly to the stimulus, hence exploiting their full potential for use in sophisticated and dynamic applications have been started lately. Researchers are keen to incorporate shape memory and self-healing properties. Shape memory hydrogels (SMHs) are intelligent hydrogels that rely on a shape memory polymer matrix and are sensitive to external stimuli such as temperature, light, and pH, and they are able to change their properties based on the external stimulus. SMHs are sensitive to self-healing through chemical and physical bonds, and they are able to heal themselves upon being damaged. SMHs can be deformed largely and revert to their former state based on an external stimulus. This review comprehensively covers the basic mechanisms, properties, and various applications of SMHs. An effort is made to explore the inclusion of AI and ML within SMH systems, pointing out their recent roles and potential benefits, with new opportunities. Besides, this review covers the current challenges for SMHs and presents prospects for future studies on their development.

Infantile hemangiomas (IHs) can lead to significant complications during the proliferative phase, particularly in thick lesions that are not adequately controlled by topical timolol due to its limited skin penetration. Oral propranolol is effective but limited by systemic side effects and resistance. To overcome these challenges, we developed a novel barbed microneedle (MN) system for depth-specific dual-drug delivery. Bleomycin (BLM) is loaded in the needle tips for deep ablation, while timolol (TM) is incorporated in the base hydrogel for superficial vasoconstriction, enabling synergistic therapy (TM-BLM@MN). The barbed structure secured prolonged retention in vivo. In vitro, the TM-BLM@MN significantly inhibited hemangioma stem cell proliferation, migration, and tube formation. In vivo, treatment of TM-BLM@MN achieved a 1.93-fold greater reduction in tumor volume compared to controls and markedly suppressed pathological angiogenesis by histology. TM-BLM@MN as a minimally invasive platform demonstrates high efficacy for thick IH and holds strong potential for clinical translation and home-based therapy.

Radiation-induced hypothyroidism (RIHT) is a frequent consequence of head and neck radiotherapy, driven by oxidative stress, inflammation, and immune dysregulation. Current therapies address hormonal imbalance but not underlying tissue damage. Strategies involving macrophage modulation and oxidative stress reduction represent a promising target for restoring homeostasis in the irradiated thyroid. Electrospun polycaprolactone (PCL) scaffolds incorporating 0.5%-3% adenosine are developed to provide localized modulation of oxidative and inflammatory responses. Adenosine incorporation does not alter scaffold morphology or stability. In vitro studies demonstrate that 1% adenosine scaffolds enhance thyrocyte proliferation, epithelial cohesion, and expression of antioxidant enzymes glutathione peroxidase (GPX1) and catalase (CAT), while reducing markers of senescence and apoptosis (RGN, CDKN2A, CASP3). In parallel, adenosine scaffolds regulate THP-1-derived macrophage behaviour, promoting a pro-reparative CD206+/CD163+ phenotype and reducing CD86, CD80, and TNFα expression associated with inflammatory activation. This study identifies fibrosis and oxidative stress as contributors to RIHT and demonstrates the feasibility of adenosine-blended scaffolds as a platform for targeting these mechanisms. Macrophage heterogeneity was characterized in the thyroid pre- and post-irradiation for an immune-guided design. The resulting scaffolds provide a targeted strategy to modulate key contributors to RIHT pathology, laying the groundwork for future in vivo validation.

Critical-sized maxillofacial bone defects remain a major clinical challenge due to the limited osteoinductive capacity of existing biomaterials. While cell adhesion is recognized as an initiating event in bone regeneration, how adhesive interactions integrate biochemical and mechanical cues to regulate osteogenic commitment remains poorly understood. Here, we demonstrate that the synergistic coupling of mechanical stimulation (MS) and icariin (ICA) promotes osteogenic differentiation through the integrin β₁/β-actin/YAP signaling axis. By combining single-cell adhesion force measurements using a robotic micro-operating system with biomimetic three-dimensional scaffolds, we show that MS-ICA coupling enhances osteoblast adhesion, induces actin cytoskeletal remodeling, and facilitates YAP nuclear translocation, thereby activating osteogenic gene expression. Genetic or pharmacological disruption of integrin β₁, β-actin, or YAP abrogated the pro-osteogenic effects, confirming their essential roles in this mechanotransductive pathway. In a rabbit mandibular defect model, ICA-functionalized scaffolds under physiological loading significantly accelerated bone regeneration. Collectively, these results elucidate a mechanistic link between cell adhesion and lineage specification and establish a design principle for biomaterials that integrate mechanical and biochemical regulation to enhance bone regeneration.

Ferroptosis plays a critical role in postmenopausal osteoporosis (PMOP) pathogenesis, but targeted therapies remain limited. In this study, we have developed bone-targeting selenium-doped carbon dots conjugated with alendronate (ASCDs) with the dual functionality of suppressing ferroptosis and promoting osteogenesis. In vitro, ASCDs mitigated erastin-induced ferroptosis in osteoblasts and bone-marrow mesenchymal stem cells by activating the system Xc^--GSH-GPX4 antioxidant pathway, which reduced lipid peroxidation and restored mitochondrial function. Furthermore, ASCDs induced ALP activation and mineralized nodule formation under ferroptosis conditions, and enhanced expression of osteogenic markers, including RUNX2, OPN, and OSX. In vivo, ASCDs demonstrated superior efficacy compared to non-targeted selenium-doped carbon dots (SCDs), significantly reversing trabecular bone loss in ovariectomized mice, reducing osteoclast activity, and suppressing ferroptosis in bone tissue. Proteomics and biochemical analyses further validated that ASCDs exert therapeutic effects by rescuing GPX4 expression and redox homeostasis. Such dual-functional carbon dots present a targeted strategy to treat PMOP by concurrently inhibiting ferroptosis and restoring bone formation.

Drug development is hindered by high attrition rates, with clinical trial failures accounting for 90% of unsuccessful candidates and 60% of R&D costs, often due to unanticipated cardiotoxicity. Existing models lack physiological relevance, particularly the vascular component critical for drug distribution and cardioprotection. To address this, we developed a heart-on-a-chip (HoC) platform integrating human induced pluripotent stem cell (iPSC)-derived cardiomyocytes, cardiac fibroblasts, and endothelial cells from a single cell line, ensuring genetic uniformity and native-like cell-cell interactions. The tri-culture system maintained >90% cell viability under perfusion for 7 days and exhibited functional maturity, as demonstrated by expected chronotropic responses to the β-agonist isoproterenol. Crucially, the inclusion of endothelial cells mitigated doxorubicin-induced cardiotoxicity, a protective effect absent in conventional models, highlighting the endothelial layer's role in replicating in vivo drug responses. By combining physiological mimicry with scalability, this HoC platform offers a transformative tool for improving preclinical cardiotoxicity assessment and reducing reliance on animal models.

Persistent inflammation and infection within a macerated microenvironment critically hinder skin wound healing. Here, we report an engineered to regulate liquid transport and promote wound repair. The composite consists of a hydrophobic top layer, a hydrophilic gel-forming middle layer, and two drug-loaded fibrous layers with tunable hydrophobicity. This gradient architecture from hydrophobic to hydrophilic layers integrates directional liquid transport, efficient water absorption, breathability, and mechanical robustness. The diode-like liquid transport behavior enables pH-responsive, dual-drug release, providing synergistic anti-inflammatory and antibacterial effects. Consequently, this design minimizes maceration while maintaining a moist, bioactive environment favorable for tissue regeneration. Both in vitro and in vivo studies confirm the composite's pronounced antioxidant and hemostatic activities, along with its ability to markedly reduce infection and inflammation, thereby accelerating wound closure and promoting new tissue formation. This work presents a multifunctional therapeutic platform and highlights the significant clinical potential of this hierarchical composite for advanced wound management.

The dynamic physicochemical environment of healing wounds provides valuable diagnostic information, with pH serving as a key biomarker for infection, inflammation, and tissue regeneration. However, the development of flexible, biocompatible, and stable pH sensors that can be seamlessly integrated into wearable platforms remains challenging. Here, we report a strategy to fabricate electrically conductive, pH-responsive bioelectronic sensors based on ultrathin polypyrrole (PPy) films deposited via oxidative chemical vapor deposition (oCVD). The resulting flexible sensors enable monitoring of physiologically relevant pH changes (4-9) and exhibit modulation of electrical conductivity up to two orders of magnitude, reaching 304 S.cm^-1 (pH 4). Grazing-incidence wide-angle X-ray scattering reveals enhanced structural order and efficient π-π stacking with increasing dopant concentration, leading to improved charge transport. Complementary spectroscopic analyses demonstrate that reversible protonation-deprotonation of the PPy backbone, governed by dopant counterion exchange, underlies the pH-dependent electrical response. The all-polymer pH sensors display high sensitivity, stability, and repeatability. Moreover, the substrate-independent nature of oCVD enables the fabrication of pH-sensing patches and spatially patterned micro-islands, facilitating seamless integration into smart wound dressings for spatiotemporally resolved bioelectronic monitoring. This work advances the design of flexible, wearable pH sensors and provides opportunities for real-time wound-healing monitoring.