Advanced Healthcare Materials最新文献

Efficient drug delivery remains a significant challenge in modern medicine and pharmaceutical research. Micrometer-scale robots have recently emerged as a promising solution to enhance the precision of drug administration through remotely controlled navigation within microvascular networks. Real-time tracking is crucial for accurate guidance and confirmation of target arrival. However, deep-tissue monitoring of microscopic structures in vivo is limited by the sensitivity and spatiotemporal resolution of current bioimaging techniques. In this study, biocompatible microrobots are synthesized by incorporating indocyanine green and iron oxide nanoparticles onto copper phosphate microflowers using a layer-by-layer approach, enhancing optoacoustic contrast and enabling magnetic navigation. Magnetic control of these particles under optoacoustic guidance is demonstrated in vivo. Furthermore, super-resolution optoacoustic imaging, achieved through individual particle tracking, is shown to enable the characterization of microvascular structures and quantification of blood flow. The combination of the microflowers' high carrying capacity, in vivo actuation, and high-resolution tracking capabilities opens new opportunities for precise microvascular targeting and localized administration of theranostic agents via intravascular routes.

Eosinophils play a crucial role as effector cells in asthma pathogenesis, with their differentiation being tightly regulated by metabolic mechanisms. While the involvement of iron in various cellular processes is well known, its specific role in eosinophil differentiation has largely remained unexplored. This study demonstrates that iron levels are increased during the differentiation process from eosinophil progenitors to mature and activated eosinophils in the context of allergic airway inflammation. Through experiments involving iron chelators, supplements, and iron-deficient or iron-enriched diets, the indispensable role of iron in eosinophil lineage commitment both in vitro and in vivo is demonstrated. Remarkably, iron chelation effectively suppresses eosinophil differentiation and alleviates airway inflammation in a house dust mite(HDM)-induced mouse model of allergic asthma. Mechanistically, iron promotes the expression of transcription factors that enforce eosinophil differentiation, and maintains mitochondrial metabolic activities, leading to specific metabolic shifts within the tricarboxylic acid (TCA) cycle, with succinate promoting eosinophil differentiation. Overall, this study highlights the function of iron and underlying metabolic mechanisms in eosinophil differentiation, providing potential therapeutic strategies for asthma control.

Peripheral nerve injury is a common disease resulting in reversible and irreversible impairments of motor and sensory functions. In addition to conventional surgical interventions such as nerve grafting and neurorrhaphy, nerve guidance conduits are used to effectively support axonal growth without unexpected neuroma formation. However, there are still challenges to secure tissue-mimetic mechanical and electrophysiological properties of the conduit materials. Herein, the phenylborate-tethered hydrogel-assisted doping effect is elucidated on conductive polymers, enhancing peripheral nerve regeneration when used as a sutureless bandage on the injured nerve. The adhesive and conductive nerve bandage consists of biocompatible hyaluronic acid hydrogel microfibers produced by electrospinning, followed by in situ conductive polypyrrole polymerization on the fibrous mat. Particularly, phenylborate groups enable high adsorption of pyrrole without mechanical crack on the hydrogel network and allow tissue-like stretchability and on-nerve adhesiveness. In a rat crushed nerve injury model, the nerve bandage can effectively promote nerve regeneration through stable sutureless wrapping followed by great electrical transmission on the defect region, showing anatomical and functional recovery of the nerve tissues and preventing muscular atrophy. Such hydrogel fibrous bandages will be a promising surgical dressing to be combined with versatile biomedical devices/materials for peripheral nerve repair.

Renal ischemia/reperfusion injury (IRI) is a common form of acute kidney injury. The basic mechanism underlying renal IRI is acute inflammation, where oxidative stress plays an important role. Although bilirubin exhibits potent reactive oxygen species (ROS)-scavenging properties, its clinical application is hindered by problems associated with solubility, stability, and toxicity. In this study, BX-001N, a synthetic polyethylene glycol-conjugated bilirubin 3α nanoparticle is developed and assessed its renoprotective effects in renal IRI. Intravenous administration of BX-001N led to increase uptake in the kidneys with minimal migration to the brain after IRI. Peri-IRI BX-001N administration improves renal function and attenuates renal tissue injury and tubular apoptosis to a greater extent than free bilirubin on day 1 after IRI. BX-001N suppressed renal infiltration of inflammatory cells and reduced expression of TNF-α and MCP-1. Furthermore, BX-001N increases renal tubular regeneration on day 3 and suppresses renal fibrosis on day 28. BX-001N decreases the renal expressions of dihydroethidium, malondialdehyde, and nitrotyrosine after IRI. In conclusion, BX-001N, the first Good Manufacturing Practice-grade synthetic bilirubin-based nanomedicine attenuates acute renal injury and chronic fibrosis by suppressing ROS generation and inflammation after IRI. It shows adequate safety profiles and holds promise as a new therapy for renal IRI.

Bone defects caused by fractures and diseases often do not heal spontaneously. They require external agents for repair and regeneration. Bone tissue engineering is emerging as a promising alternative to traditional therapies like autografts and allografts. Nanobiomaterials enhance osteoblast resistance to harsh environments by promoting cell differentiation. Black phosphorus (BP), a novel 2D material in biomedicine, displays unique osteogenic and antimicrobial properties. However, BP nanosheets still face clinical limitations like rapid degradation and high-dose cytotoxicity. To address these, the introduction of amino-silicon phthalocyanine (SiPc-NH₂) is investigated to see if it can enhance BP dispersion, reduce BP oxidation, and improve stability and safety for better osteogenesis and antibacterial effects through noncovalent interactions (van der Waals, π-π stacking and electrostatic interactions). Here, the self-healing hydrogel is successfully designed using a step-by-step co-assembly of BP and SiPc-NH_2. SiPc-NH₂ as a "structural stabilizer" of BP nanosheets reconstructed well-dispersed BP-SiPc-NH₂ nanosheets, which improves the biocompatibility of BP, reduces oxidation and enhances photothermal conversion, guaranteeing osteogenic and antimicrobial properties. Furthermore, findings show BP-SiPc-NH₂-induced mitochondrial changes support osteogenesis by regulating the crosstalk between Hippo and Wnt signaling pathways-mediated mitochondrial homeostasis, and boosting cellular bioenergetics. Overall, this mitochondrial morphology-based BP-SiPc-NH₂ strategy holds great promise for bone repair applications.

Engineered modifications of nanomaterials inspired by nature hold great promise for disease-specific imaging and therapies. However, conventional polyethylene glycol modification is limited by immune system rejection. The manipulation of gold nanorods (Au NRs) modified by endogenous proteins (eP@Au) is reported as an engineered biomodulator for enhanced breast tumor therapy. The results show that eP@Au NRs neither activate inflammatory factors in vitro nor elicit rejection of immune responses in vivo. Tumor-specific eP@Au NRs exhibit a dual-modal imaging capability and trigger a mild photothermal effect under near-infrared light irradiation, enabling highly efficient imaging and therapy of tumors. Transcriptome sequencing and confirmatory experiments reveal that the antitumor effect is mainly attributed to the repression of PI3K-Akt/MAPK signaling pathways at the molecular level. This powerful and surprising in situ eP-regulated biomodulation demonstrates the advantages of convenient fabrication, inert immunogenicity, and biocompatibility, providing an alternative strategy for biomedical imaging and therapy.

Current biodegradable materials are facing many challenges when used for the design of implantable devices because of shortcomings such as toxicity of crosslinking agents and degradation derivatives, limited cell adhesion, and limited immunological compatibility. Here, a class of materials built entirely of stable protein is designed using a simple protocol based on salt-assisted compaction of albumin, breaking with current crosslinking strategies. Salt-assisted compaction is based on the assembly of albumin in the presence of high concentrations of specific salts such as sodium bromide. This process leads, surprisingly, to water-insoluble handable materials with high preservation of their native protein structures and Young's modulus close to that of cartilage (0.86 MPa). Furthermore, these materials are non-cytotoxic, non-inflammatory, and in vivo implantations (using models of mice and rabbits) demonstrate a very slow degradation rate of the material with excellent biocompatibility and absence of systemic inflammation and implant failure. Therefore, these materials constitute promising candidates for the design of biodegradable scaffolds and drug delivery systems as an alternative to conventional synthetic degradable polyester materials.

Therapeutic strategy for efficiently targeting cancer cells needs an in-depth understanding of the cellular and molecular interplay in the tumor microenvironment (TME). TME comprises heterogeneous cells clustered together to translate tumor initiation, migration, and proliferation. The TME mainly comprises proliferating tumor cells, stromal cells, blood vessels, lymphatic vessels, cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), and cancer stem cells (CSC). The heterogeneity and genetic evolution of metastatic tumors can substantially impact the clinical effectiveness of therapeutic agents. Therefore, the therapeutic strategy shall target TME of all metastatic stages. Since the advent of nanotechnology, smart drug delivery strategies are employed to deliver effective drug formulations directly into tumors, ensuring controlled and sustained therapeutic efficacy. The state-of-the-art nano-drug delivery systems are shown to have innocuous modes of action in targeting the metastatic players of TME. Therefore, this review provides insight into the mechanism of cancer metastasis involving invasion, intravasation, systemic transport of circulating tumor cells (CTCs), extravasation, metastatic colonization, and angiogenesis. Further, the novel perspectives associated with current nanotherapeutic strategies are highlighted on different stages of metastasis.

The hydrogel adhesives with strong tissue adhesion and biological characteristics adhm202404447are urgently needed for injury sealing and tissue repair. However, the negative correlation between tissue adhesion and the mechanical strength poses a challenge for their practical application. Herein, a bio-inspired cohesive enhancement strategy is developed to prepare the hydrogel adhesive with simultaneously enhanced mechanical strength and tissue adhesion. The double cross-linked network is achieved through the cooperation between polyacrylic acid grafted with N-hydroxy succinimide crosslinked by tannic acid and cohesion-enhanced ion crosslinking of sodium alginate and Ca²⁺. Such a unique structure endows the resultant hydrogel adhesive with excellent tissue adhesion strength and mechanical strength. The hydrogel adhesive is capable of sealing various organs in vitro, and exhibits satisfactory on-demand removability, antibacterial, and antioxidant properties. As a proof of concept, the hydrogel adhesive not only effectively halts non-compressible hemorrhages of beating heart and femoral artery injury models in rats, but also accelerates the healing of infected wound by inhibiting bacteria and reducing inflammation. Overall, this advanced hydrogel adhesive is promising as an emergency rescue adhesive that enables robust tissue closure, timely controlling bleeding, and promoting damaged tissue healing.

Cell-instructive polymer hydrogels are instrumental in tissue engineering for regenerative therapies. Implementing defined and selective responsiveness to external stimuli is a persisting challenge that critically restricts their functionality. Addressing this challenge, this study introduces a versatile, modular hydrogel system composed of four-arm poly(ethylene glycol)(starPEG)-peptide and glycosaminoglycan(GAG)-maleimide conjugates. The gel system features a small peptide sequence that is selectively cleaved by the coagulation factor FXa. In a cell culture environment, where active FXa is absent, the hydrogel remains stable, providing a conducive matrix for the growth of complex tissue structures or organoids. Upon the introduction of FXa, the hydrogel is designed to disintegrate rapidly, enabling the gentle release of the cultivated tissues without impairing their functionality. The efficacy of this approach is demonstrated through the ex vivo development, detachment, and transplantation of human corneal endothelial lamellae, achieving sizes relevant for clinical application in Descemet Membrane Endothelial Keratoplasty (DMEK). Furthermore, the practicality of the hydrogel system is validated in vitro using a de-endothelialized porcine cornea as a surrogate recipient. Since the FXa-cleavable peptide can be integrated into a variety of multifunctional hydrogels, it can pave the way for next-generation scaffold-free tissue engineering and organoid regenerative therapies.