Advanced Healthcare Materials最新文献

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.

Bladder cancer is a major global health challenge with high recurrence and mortality. Despite advances in surgery and chemotherapy, immune checkpoint inhibitors (ICIs) have limited effectiveness due to poor immune infiltration and inadequate responses. To address these issues, we developed an ultrasound-responsive Mn/Se-NE@FCS nanozyme (NE) that activates both STING signaling and PANoptosis, a novel multi-pathway cell death mechanism involving apoptosis, necroptosis, and pyroptosis. This dual-action system enhances ROS production, mitochondrial dysfunction, and immunogenic cell death (ICD) in tumors, promoting dendritic cell (DC) maturation, CD8⁺ T-cell infiltration, and memory T-cell expansion. The Mn/Se-NE@FCS nanozyme showed superior tumor control and synergized with PD-1 blockade in murine bladder cancer models. Histological and flow cytometry analyses confirmed that the treatment remodels the tumor microenvironment, driving immune activation and T-cell priming. This strategy offers a promising nanoimmunotherapy approach for bladder cancer, using ultrasound-triggered activation to induce multi-pathway tumor cell death and stimulate long-lasting systemic immunity.

The integration of autophagy regulation with photothermal therapy (PTT) presents a promising therapeutic strategy for addressing triple-negative breast cancer (TNBC), a condition where current treatment modalities are hindered by limited tissue penetration and therapeutic resistance. In this study, we have developed a dual-layer metal-organic framework (MOF) integrated microneedle patch (DMMN) designed to facilitate sequential dissolution for combination therapy, encompassing sensitized PTT, autophagy regulation, and chemotherapy. The outer layer of the microneedle is constructed from a hyaluronic acid (HA) matrix, which is integrated with carboxyl MOFs loaded with Apoptozole (Az), an Hsp70 inhibitor. This configuration maintains rapid dissolution behavior and exhibits favorable mechanical properties. The core layer consists of hyaluronic acid methacryloyl (HAMA), which encapsulates photothermal agents and degrades slowly to enable deep-tissue penetration for effective PTT. The incorporated MOFs enhance the mechanical strength of the HA-based microneedles and improve the loading efficiency of hydrophobic drugs. Upon tissue penetration, the released Az inhibits Hsp70, thereby sensitizing cancer cells to PTT, promoting lysosome-mediated apoptosis, and suppressing autophagy. This dual-layer MOF-integrated microneedle system offers a novel approach to overcoming the challenges associated with TNBC treatment.

Skin Wound Healing

A dual-head spray device delivers a cell-loaded fibrinogen bioink enriched with glycosaminoglycans and collagen onto a wound to promote wound healing. This approach enables minimally invasive skin regeneration and shows comparable healing efficacy to autografts in preclinical models. More details can be found in the Research Article by Elena López-Ruiz, Juan Antonio Marchal, and co-workers (DOI: 10.1002/adhm.202500702).

Lipid nanoparticles (LNPs) have become the leading platform for delivering genetic material, gaining global recognition through the success of mRNA-based COVID-19 vaccines such as mRNA-1273 (SpikeVax, Moderna) and BNT162b2 (Comirnaty, BioNTech/Pfizer). Yet, while RNA-LNPs have reached clinical maturity, their DNA counterparts remain comparatively underexplored, despite holding great promise for gene replacement and genome-editing therapies. In this review, we turn the spotlight on DNA-loaded LNPs, examining how their structure, composition, and biological behavior differ from RNA-LNPs, their natural point of reference, and from earlier lipid-based systems such as cationic liposome/DNA complexes (lipoplexes). DNA-LNPs tend to form larger, more heterogeneous, and often multilamellar particles due to the intrinsic stiffness and high charge density of DNA. These distinctive features call for dedicated design strategies, including the use of cationic lipids, pre-condensation agents, and optimized PEGylation schemes. Moreover, DNA profoundly influences the biomolecular corona that forms in biological fluids, which in turn shapes immune recognition, circulation, and tissue targeting. By highlighting these unique physical and biological challenges, this review underscores the need to move beyond simply adapting RNA-based formulations. Instead, a cargo-informed design approach will be key to unlocking the full therapeutic potential of DNA-LNPs in next-generation gene delivery.

Cancer Adjuvant Therapy

In the Research Article (DOI: 10.1002/adhm.202502779), Hao Zhang and co-workers systematically delineate an oncotherapeutic strategy, which activates sodium alginate hydrosols by dual-mode hybrid discharge plasma, enabling direct tumor-cell clearance while robustly inducing immunogenic cell death to initiate antitumor immune responses, demonstrating its translational potential as an adjuvant cancer therapy.

Inflammation underlies the progression of both acute and chronic diseases, yet conventional therapies remain limited by systemic side effects, poor compliance, and insufficient responsiveness to dynamic pathological cues. Nitric oxide (NO), a gaseous mediator with high diffusivity and membrane permeability, is aberrantly overproduced in diverse inflammatory conditions and thus represents a promising trigger for responsive drug delivery. Here, we present a NO-responsive microneedle (NOR-MN) platform that exploits pathological NO for controlled transdermal therapy. The system integrates a NO-cleavable crosslinker that degrades selectively in NO-rich environments, enabling NO-dependent release of encapsulated drugs while simultaneously scavenging excess NO to mitigate inflammation. This dual-functional design combines disease-responsive delivery with intrinsic anti-inflammatory activity, offering a minimally invasive and therapeutically adaptable platform. The therapeutic potential of NOR-MNs was validated in both acute and chronic inflammatory models. In lipopolysaccharide-induced peritonitis, dexamethasone-loaded NOR-MNs achieved NO-triggered release, suppressed cytokine production, alleviated hepatic toxicity, and improved tissue pathology. In diabetes mellitus, insulin-loaded NOR-MNs responded to elevated NO levels to restore glucose homeostasis and enhanced insulin responsiveness in vitro. Collectively, these findings establish NO-responsive microneedles as an innovative stimuli-responsive strategy with broad applicability for the treatment of inflammation-driven diseases.

This article addresses the unmet clinical need of scaffolds for bone regeneration that can combine osteogenic properties, such as the promotion of bone marrow stem cell differentiation into osteoblasts, with the ability to withstand cyclic loading. In our previous study, we demonstrated that discs of SiO₂-CaO_CME/poly(tetrahydrofuran)/poly(caprolactone) hybrids or their dissolution products can drive terminal osteogenic differentiation of human bone marrow stromal cells (h-BMSCs) in vitro. The current study shows that the 3D-printed hybrid scaffolds with physiologically relevant 3D architecture further promote h-BMSC osteogenesis. The 3D-printed scaffolds support spatially organized cell behavior in an environment mirroring conditions relevant to off-the-shelf implant applications. Primary cellular functions, including viability, adhesion, and proliferation, were maintained across 3D scaffold surfaces and within inter-strut regions. osteogenic commitment was evidenced by the upregulation of lineage-specific transcripts, hydroxyapatite deposition, and the organized assembly of extracellular matrix (ECM) proteins. Our results demonstrate that 3D-printed scaffolds drive osteogenesis by modulating cell metabolism, inducing osteogenic morphological transitions, and promoting the expression of osteocalcin and collagen type I alpha 1 chain, alongside hydroxyapatite matrix mineralization. Collectively, our findings highlight the SiO₂-CaO_CME/poly(tetrahydrofuran)/poly(caprolactone) scaffold's strong osteogenic properties-driven by composition, surface architecture, and ion release - and its promise for clinical bone regeneration.