Biomaterials Science最新文献

Neuroregeneration has drawn scientific attention due to its therapeutic potential for neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and traumatic brain injury (TBI). A major obstacle in delivering neuroregenerative and neuroprotective drugs is crossing the blood-brain barrier (BBB)-a selective, physiological barrier that protects the central nervous system (CNS) from circulating toxins and pathogens. While this protective role is essential for maintaining CNS homeostasis, it also limits therapeutic efficacy and increases the risk of systemic side effects due to off-target accumulation. To overcome these challenges, recent advances in nanoparticle engineering have focused on enhancing BBB transcytosis by employing biologically inspired surface modifications. In this review, we highlight three mechanistically distinct approaches: (1) transporter-mediated transcytosis (TMT), which uses glucose or amino acid conjugation; (2) receptor-mediated transcytosis (RMT) via ligands such as transferrin or angiopep-2; and (3) adsorptive-mediated transcytosis (AMT), utilizing cationic polymer coatings or cell-penetrating peptides (CPPs).

Hydrogen synergistic therapy, an emerging and promising strategy in tumor treatment, has been bolstered by nanotechnology to establish a stable and multifunctional foundation for its implementation. Hydrogen-synergistic diagnostic and therapeutic nanoplatforms (HSDT-NPs), a novel type of tool for tumor treatment, integrate hydrogen therapy with various tumor diagnostic and therapeutic strategies, significantly enhancing the efficiency and specificity of tumor treatment, which is crucial for achieving precision therapy at the tumor site. The construction of HSDT-NPs relies on the design of hydrogen nanomaterials and the selection and assembly of synergistic units. Through HSDT-NPs, the synergistic effects between hydrogen therapy and other strategies are markedly enhanced, not only improving the efficacy of traditional therapies on tumors but also effectively protecting normal cells. Based on different material types, this study explores the construction strategies of HSDT-NPs. Subsequently, focusing on the collaborative treatment modes, it delves into the synergistic mechanisms of HSDT-NPs. Our work aims to offer new perspectives and innovative approaches for advancing cancer treatment based on hydrogen therapy research.

Epilepsy is one of the most common neurological disorders, with current antiepileptic drugs (AEDs) being ineffective in up to 30% of patients. Moreover, the therapeutic efficacy of existing AEDs is significantly limited by the blood-brain barrier (BBB). The neuropeptide Y₂ receptor is a potential antiepileptic target, with NPY (3-36) acting as its selective agonist. GW2580, an inhibitor of the colony-stimulating factor 1 receptor, has neuroprotective potential. In this study, a novel nanocomposite, NPY@ZIF-RG, was synthesized by covalently conjugating NPY (3-36) onto the surface of GW2580-encapsulated nano-Zeolitic imidazolate framework-90 (ZIF-90) via a simple post-modification. The biosafety of NPY@ZIF-RG was evaluated in vitro and in vivo. The BBB permeability and its effects on neuroinflammation and neuronal excitability were assessed. The therapeutic efficacy of NPY@ZIF-RG was explored using immunohistochemistry, quantitative real-time polymerase chain reaction, and behavioral tests in a mouse model of kainic acid-induced acute epilepsy. The results indicated that NPY@ZIF-RG exhibited excellent biocompatibility and efficient BBB penetration. Furthermore, it exerted beneficial therapeutic effects by inhibiting microglia-mediated inflammation and reducing excitatory glutamate release. NPY@ZIF-RG alleviated hippocampal neuronal loss and cognitive dysfunction by co-delivering GW2580 and NPY (3-36), which exerted synergistic neuroprotective and anti-inflammatory effects. This study provides a promising nanocomposite drug-delivery system for the treatment of epilepsy.

Ischemic stroke continues to be a leading cause of death and long-term disability worldwide. However, the clinical use of intravenous tissue plasminogen activator (tPA) is constrained by its rapid systemic clearance and the risk of hemorrhagic transformation (HT). In this study, we present an MMP-9-responsive PLGA-based nanocarrier (tPLGA) that enables thrombus-microenvironment triggered release of tPA. When combined with Bindarit, an inhibitor of the CCL2/CCR2 pathway, this strategy achieves both targeted thrombolysis and effective suppression of HT. In mouse thrombosis models, tPLGA mediated precise spatiotemporal tPA delivery, enhancing clot dissolution. Concurrent CCL2/CCR2 blockade reduced neutrophil infiltration, preserved blood-brain barrier (BBB) integrity, and prevented HT. Behavioral, histological, and biosafety assessments confirmed improved neurological recovery and translational potential. This work establishes a therapeutic platform integrating precision thrombolysis with immune modulation for a safer and more effective treatment of ischemic stroke.

Hepatocellular carcinoma (HCC) is one of the most severe malignancies in modern society, and is known as an "inflammatory tumor", rarely benefiting from immunotherapies. In the inflammatory microenvironment of precancerous HCC, immune cells and stromal cells are transformed from an anti-tumor type into a pro-tumor type by stimuli of different inflammatory factors, oxidative stress and key signaling pathways. This evolution fosters a profoundly immunosuppressive niche, culminating in T cell exhaustion and the failure of immune checkpoint inhibitors (ICIs), which are further limited by systemic adverse events and low response rates. Emerging nanotherapeutic strategies, designed to precisely target and remodel the HCC immune landscape, offer a promising avenue to overcome these limitations. This review analyzes the mechanistic links between inflammation-driven immune suppression and progression. We evaluate and categorize cutting-edge nanomedicine approaches designed to initiate immune responses, reverse immunosuppression, and liberate T cell function. Furthermore, we discuss current challenges in clinical translation, particularly those stemming from the physicochemical properties and in vivo behavior of nanocarriers, and proposed strategic directions for next-generation inflammation-targeted nanotherapeutic design, providing new perspectives for breaking the cycle of immune tolerance in HCC.

Water contamination can trigger Escherichia coli (E. coli) infections, which are extremely harmful to humans. Healthy individuals typically recover within a week from symptoms such as severe abdominal pain, diarrhea, and vomiting. However, children and elderly individuals are at a higher risk of developing kidney dysfunction. To kill these life-threatening bacteria, reactive oxygen species (ROS) generating zinc oxide (ZnO) nanomaterials were synthesized via a sustainable green approach using medicinally rich Calotropis procera (C. procera) flower extract. The functional groups and wurtzite crystalline structure of the synthesized ZnO were revealed by Fourier transform infrared (FT-IR) spectroscopy and powder X-ray diffraction (PXRD) analysis, respectively. Scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HR-TEM) demonstrated the formation of pineapple-like nanoleaves (PNLs), with sizes ranging from 61 to 122 nm, along with well-defined lattice fringes, confirming their nanoscale dimensions and high crystallinity. Energy-dispersive X-ray (EDX) spectroscopy further confirmed the elemental composition (1 : 1 ratio of Zn and O in ZnO) and purity of the ZnO nanomaterials. Antioxidant activity was measured using the standard 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay at different concentrations. Lipid peroxidation (LPO) exhibited strong ROS-generating capability, leading to membrane protein damage and ultimately cell death. Minimum inhibitory concentration (MIC) analysis revealed selective antimicrobial activity against Gram-negative E. coli, while polymerase chain reaction (PCR) confirmed DNA fragmentation, supporting bacterial cell cleavage. The ZnO PNLs exerted excellent cytotoxic effect against A431 skin cancer cells, with an IC₅₀ value of 70.41 μM. Increased intracellular ROS levels induced apoptotic morphological changes in A431 cells. Confocal scanning microscopy revealed enhanced fluorescence in A431 human epidermal cells treated with ZnO PNLs, indicating concentration-dependent ROS generation and cellular internalization. Inverse molecular docking analysis was further performed to identify favorable binding affinity scores against 11 skin cancer-associated protein targets at the molecular level. Overall, ZnO PNLs synthesized using the C. procera flower extract exhibited excellent biocompatibility and potent antibacterial and anticancer activities against E. coli and A431 skin cancer cells.

Multifunctional nanoplatforms that integrate both exogenous stimuli-induced mild photothermal therapy (mPTT) and endogenous stimuli-responsive chemodynamic therapy (CDT) have shown great potential for precise and safe cancer treatment. However, the effective interplay among nanoplatform components to enhance the synergistic effects of mPTT and CDT still suffers from distinct limitations during implementation. Here, we present a novel multifunctional nanoplatform, HCuS-DOX@ZIF-8-GOX (HDZG), rationally engineered to achieve self-augmented mPTT/CDT through cascade regulation under near-infrared (NIR) irradiation, effectively addressing these limitations. Upon accumulation at the tumor site, the synergistic effects of GOX-catalyzed glucose consumption by inhibiting the glycolytic pathway and Zn²⁺-induced mitochondrial dysfunction accelerated adenosine triphosphate (ATP) depletion, thereby suppressing heat shock protein (HSP) expression and amplifying the efficacy of NIR-triggered mPTT. Simultaneously, reactive oxygen species (ROS) production was markedly amplified via an accelerated Fenton-like reaction, driven by elevated intracellular H₂O₂ levels produced from GOX-catalyzed glucose oxidation and the photothermal effect of hollow copper sulfide (HCuS). Moreover, glutathione (GSH) depletion was intensified by DOX-induced ROS production and the Cu⁺/Cu²⁺ cycling reaction, collectively contributing to a markedly improved CDT effect. Consequently, HDZG NPs demonstrated self-enhanced antitumor effects through NIR-induced mild photothermal/chemodynamic synergistic therapy, offering a promising strategy to improve the efficacy of multimodal cancer treatments.

Chronic ultraviolet (UV) exposure drives skin photoaging by accelerating collagen degradation, disrupting extracellular matrix (ECM) organization, and impairing barrier function. Although recombinant collagens offer safety advantages over animal-derived counterparts, their limited self-assembly capability and inadequate structural stability restrict their therapeutic potential. Here, we develop injectable tetrakis(hydroxymethyl)phosphonium chloride (THPC)-crosslinked self-assembled recombinant type I collagen (SARCI) nanofibers with tunable crosslinking densities for the regenerative repair of photoaged skin. THPC-mediated crosslinking markedly enhanced the thermal stability, mechanical rigidity, and enzymatic resistance of the nanofibers. In vitro, all THPC-crosslinked SARCI formulations significantly promoted fibroblast migration, proliferation, and differentiation. In a UV-induced photoaging mouse model, THPC-crosslinked SARCI demonstrated excellent biocompatibility and effectively restored epidermal structure, increased dermal density, improved barrier integrity, and promoted robust collagen regeneration. Transcriptomic analysis further suggested that THPC-crosslinked SARCI mitigates UV-induced ECM degradation by modulating MAPK signaling and maintaining tissue homeostasis. Collectively, these findings establish THPC-crosslinked SARCI as a structurally robust, highly biocompatible, and functionally stable recombinant collagen implant with strong translational potential for the treatment of photoaged skin.

Correction for 'Ciprofloxacin-loaded bioadhesive hydrogels for ocular applications' by Islam A. Khalil et al., Biomater. Sci., 2020, 8, 5196-5209.

Chronic wounds have emerged as a major healthcare challenge due to their prolonged healing cycle. A key feature of chronic wounds is local tissue hypoxia, resulting in insufficient oxygenation of the wound microenvironment. While traditional therapies like hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) alleviate wound hypoxia by oxygen supplementation, they are limited by high costs, uncertainty in sustained efficacy, and complications, restricting clinical use. Oxygen carriers, such as perfluorocarbons (PFCs) and hemoglobin (Hb), exhibit high-efficiency oxygen delivery capacity, excellent biocompatibility and cost-effectiveness. They hold enormous potential for clinical applications. This review focuses on the application of PFCs and Hb-based oxygen carriers in chronic wound therapy. It systematically elaborates on the diversified oxygen delivery strategies based on PFCs and Hb. It also quantitatively compares their oxygen delivery capabilities and analyzes their multiple synergistic biological effects. Meanwhile the review also describes the difficulties and challenges in precise delivery and clinical translation.