Advanced Healthcare Materials最新文献

Nowadays, the implantation of occluder is an effective approach for treating patent foramen ovale (PFO); however, the slow endothelialization poses significant complications associated with occlusion devices. Herein, a 4D-printed intelligent reconfigurable PFO occluder with pro-endothelialization, anti-thrombosis, and absorbability is designed. The combination of the occluder implantation and topical drug delivery of anti-thrombosis drugs offers a solution to stroke. The occluder is designed based on the biomimetic structure, facilitating the integration of mechanical response behavior compatible with cardiac tissue. In vitro degradation and in vivo histological examination demonstrate the bioabsorbability of the occluder, and the anti-thrombosis efficacy is preliminarily demonstrated through anti-thrombosis experiments. The effective expression of VWF and CD31 markers validates the superior pro-endothelial efficacy of the occluder. To summarize, the 4D-printed occluder in this work represents an accessible strategy to combat PFO through integrated occlusion and topical drug delivery.

Microbial infections, particularly those caused by drug-resistant microorganisms, pose major socioeconomic and global public health threats. Cold atmospheric pressure plasma can generate reactive oxygen and nitrogen species (RONS) with potent antimicrobial activity and minimal biosafety concerns. Plasma-activated hydrogel (PAH) has attracted increasing interest due to its 3D network structure, which can extend the lifetime of RONS. This study investigates the mechanisms governing the loading, storage, and interactions of RONS in hydrogels. The loading of RONS in hydrogels can be divided into two phases: interfacial dissolution and penetration into the hydrogel matrix. A diffusion-reaction model is established to describe the penetration process, demonstrating that RONS transport is governed by the coupling of diffusion and chemical reactions. Furthermore, vacuum freeze-dried PAH enables effective incorporation of RONS into the polymer framework for storage, with liquid-phase RONS being regenerated upon rehydration. Experimental results reveal that RONS can induce the release of NH₄ ⁺ from the AVC hydrogel, and the synergistic interaction between NH₄ ⁺ and RONS significantly enhances the bactericidal efficacy of PAH. These findings elucidate the fundamental mechanisms of RONS loading and storage in hydrogels and provide a mechanistic basis for the rational design of highly effective plasma-activated antimicrobial materials.

Uterine dysfunction arising from surgical procedures such as curettage and caesarean section often leads to adhesions, hyperplasia and fibrosis, undermining women's fertility and quality of life. Conventional pharmacological and physical therapies cannot fully restore uterine function. To overcome these limitations, we designed a composite, polysaccharide-coated silk nanofiber film as a staged scaffold to meet evolving healing demands. The hydrophilic polysaccharide layer provides early postoperative wet strength, conformability and physical isolation, while the underlying nanofibrous silk network mimics the extracellular matrix to support cell adhesion, proliferation and regeneration in later stages. In a rat model of severe uterine injury, implantation of this biodegradable film prevented postoperative adhesions and preserved reproductive capacity, achieving a fertility rate exceeding 80%. Mechanistically, the scaffold modulates the immune microenvironment by promoting M2 macrophage polarization, attenuating inflammation and accelerating tissue repair. It also upregulates angiogenic factors (VEGF-A, PDGF-BB), enhances type III collagen deposition and minimizes foreign-body reaction, collectively driving effective in situ uterine regeneration. Fabricated via aqueous electrospinning and mild coating, the scaffold is cost-effective, ecofriendly and readily scalable. As a biodegradable, staged platform tailored to dynamic uterine healing, this material offers a novel, versatile solution for clinical translation in uterine repair and broader regenerative-medicine applications.

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.