Biomaterials Science最新文献

The use of platelet-derived membranes as functional biomaterials has emerged as a promising solution to overcome major limitations in nanoparticle-based drug delivery and diagnostic platforms. These biologically inspired interfaces offer a unique combination of immune evasion, biocompatibility, and receptor-mediated targeting capabilities. This PRISMA-based systematic review synthesizes research from 2014 to 2024 on the use of platelet membranes to engineer hybrid nanocarriers for targeted delivery and detection. We critically examine strategies for membrane extraction (e.g., ultrasonication, freeze-thawing, co-extrusion), nanoparticle fusion techniques, and therapeutic functionalization using chemotherapeutics, peptides, cytokines, and photothermal agents. The resulting biomimetic nanosystems demonstrate dual diagnostic and therapeutic (theranostic) potential in diverse fields, including oncology, thrombosis, and inflammatory diseases. We further discuss the development of hybrid platforms, such as red blood cell-platelet membrane combinations, which enhance systemic circulation and targeting efficiency. The review highlights the clinical and translational relevance of platelet membrane-coated nanocarriers, with a focus on their material properties, interaction with biological barriers, and potential for immune escape. Remaining challenges include manufacturing scalability, membrane heterogeneity, and long-term safety. Continued advancement in biointerface engineering and hybridization techniques is expected to expand the applicability of these systems within the broader context of precision nanomedicine.

Four-dimensional (4D) printing enables the creation of dynamic structures that can change, altering their shape, properties, or functionality in response to stimuli over time by incorporating time as a fourth dimension. This revolutionary approach has gotten significant attention across various fields, with recent advancements in integrating smart biomaterials, biological components, and living cells into dynamic, three-dimensional (3D) constructs. Among the myriad of biomaterials available, protein-based (PB) polymers have emerged as promising due to their inherent biocompatibility, biodegradability, and ability to interact with and mimic the extracellular matrix (ECM). This review provides a comprehensive overview of 4D bioprinting, involving PB bioinks, and explores key principles, mechanisms, strategies, and types. It discusses essential requirements, such as printability, biodegradation, and mechanical integrity, as well as strategies for designing stimuli-responsive 4D bioinks. Furthermore, it comprehensively explores emerging trends in applying these bioinks for the 4D bioprinting of tissue scaffolds and their utility in disease modeling. Finally, it addresses current challenges and prospects, aiming to provide readers with a thorough understanding of recent developments in this groundbreaking technology towards adaptability in regenerative medicine and disease models.

Purpose: Early diagnosis of prostate cancer is critical for improving prognosis, but current detection techniques face limitations such as low sensitivity, high cost, and radiation risks. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in prostate cancer cells and a promising diagnostic and prognostic indicator. This study aims to develop a PSMA-targeted ultrasound contrast agent based on nanobody-modified gas vesicles (GVs) for early diagnosis of prostate cancer. Materials and Methods: GVs were extracted from Halobacterium NRC-1 (Halo). PSMA-targeting nanobodies (Nb-PSMA) were synthesized by Escherichia coli. PSMA-targeted gas vesicles (PSMA-GVs) were prepared by coupling Nb-PSMA to GVs via the intermediate coupling agent Mal-PEG₂₀₀₀-NHS. Control vesicles were prepared similarly. The targeting specificity of PSMA-GVs towards prostate cancer cells was assessed by flow cytometry and confocal microscopy using PSMA-positive PC-3 cells. In vivo contrast-enhanced ultrasound imaging of PSMA-GVs was performed in prostate cancer-bearing mice at early and advanced stages. The biocompatibility of PSMA-GVs was assessed by hemolysis tests, CCK8 cytotoxicity assays, serum biochemical assays and HE staining. Results: PSMA-GVs exhibited a uniform size, with a hydrodynamic diameter of 267.73 ± 2.86 nm, and showed a high specific binding ability to PC3 cells. In vivo ultrasound imaging of prostate cancer-bearing mice showed that PSMA-GVs had significantly slower tumor signal attenuation than Con-GVs. Our in vitro and in vivo experiments demonstrated that PSMA-GVs could bind to prostate cancer cells with higher specificity, generating stronger and longer-lasting molecular imaging signals in tumors, which presented significant advantages over Con-GVs. Immunofluorescence confirmed that PSMA-GVs crossed the vascular wall, entered the peritumoral vascular space, bound to tumor cells, and enabled PSMA-targeted molecular imaging. Additionally, PSMA-GVs showed good biocompatibility. Conclusion: Our study provides a new strategy for early ultrasound molecular imaging diagnosis of prostate cancer.

Early non-invasive diagnosis of liver fibrosis remains a significant clinical challenge. This study aimed to develop type IV collagen-targeted phase-change nanoparticles (AC-IV-PFP@NPs) for ultrasound molecular imaging (UMI), allowing accurate staging of early-stage liver fibrosis. AC-IV-PFP@NPs were prepared by conjugating anti-collagen IV antibody (AC-IV) to perfluoropentane-encapsulated liposomes via carbodiimide coupling. Physicochemical properties were characterized using transmission electron microscopy, dynamic light scattering, and confocal microscopy. In CCl₄-induced fibrotic rats representing METAVIR stages S0-S4, the targeted nanoparticles were administered intravenously. The nanoparticles displayed spherical morphology with a mean diameter of 307.92 ± 4.16 nm, high AC-IV conjugation efficiency (78.94 ± 2.83%), and a favorable biosafety profile (cell viability >87% at 6 mg mL^-1). Targeting specificity was validated both in vitro and in vivo, with fluorescence imaging showing a 3.8-fold increase in binding to fibrotic collagen IV relative to non-targeted controls (P < 0.001). CEUS signal intensity peaked at 30 min post-injection and showed a strong positive correlation with the fibrosis stage (r = 0.725, P < 0.001). ROC analysis demonstrated high diagnostic accuracy for early fibrosis: an area under the curve (AUC) of 0.949 for distinguishing S0 from S1-S4 (sensitivity 85.5%, specificity 91.7%) and an AUC of 0.923 for separating S0-S1 from S2-S4 (sensitivity 90.7%, specificity 79.2%). To date, AC-IV-PFP@NPs represent the first type IV collagen-targeted UMI platform for liver fibrosis staging in rats, offering non-invasive, real-time assessment with high sensitivity for early-stage disease (S1-S2). This approach addresses the limitations of biopsy and conventional imaging and offers a promising and transformative approach for clinical fibrosis management.

The ever-growing demand for efficient tumor-targeted delivery of high molecular-weight biomolecules calls for large pore-sized silica nanoparticles with a controlled release feature. Herein, a general organosilica precursor-enlarged micelle (OP-EM) method is introduced for facile synthesis of sub-50 nm large pore-sized hollow mesoporous organosilica nanoparticles (LPHMON). Then an extremely convenient "pore-capping" strategy is proposed to prevent the premature leakage of payloads based on polyphenol-metal coordination chemistry. Following the encapsulation of glucose oxidase (GOx) and surface coating with a tannic acid (TA)-Cu complex, the TA-Cu covered, GOx-loaded LPHMON (LPHMON-GTC) can not only avoid the GOx leakage-induced toxicity, but also go through three-step cascaded catalytic reactions (acidity-activated TA-Cu disassembly, GOx-catalyzed glucose oxidation, and a Cu²⁺-mediated Fenton-like reaction), which will facilitate the realization of endogenous tumor-specific cascaded catalytic therapy, promising precise trigger-free treatment of various cancers with minimized side effects.

Proton-conducting biopolymers have gained significant attention in various fields, such as energy-related applications, ion exchange membranes, bioelectronics, and biomedical applications. To understand their proton transport mechanisms, it is crucial to distinguish the contributions of water, particularly near the surface functional groups of the dopants (carbon dots, C-Dots) and in the vicinity of the side chain functional groups of proteins in the biopolymer. In this study, we investigate the role of surface functional groups (dopants/biopolymers) in mediating proton conduction across biopolymers (protein-based) by the doping of blue-, green-, and red-emitting C-Dots (with different extents of oxygen-containing groups) into the biopolymer. We measure the proton conduction across the doped biopolymers with varying percentages of water and different extents of oxo-group-enriched dopants with the same internal structure to understand the role of surface functional groups in individual matrices and enhance the conductivity in a controlled way. This approach may provide insights into the proton conduction pathways in biological systems and aid in the development of bioprotonic devices.

Respiratory diseases such as COPD, IPF and severe asthma are major causes of death globally, characterized by chronic inflammation and by fibrotic biomechanical remodelling of the lung ECM. However, present treatments focus on relieving inflammation and symptoms and do not address the mechanobiological aspect. This is in great part because the role of mechanobiology in disease progression and aetiology is not well-understood, indicating a need for new investigatory models. Here we introduce a combined biomaterial and 3D-organoid model, based on a hybrid biomaterial-matrix double-network gel, whose mechanical properties are dynamically photocontrolled by the application of light. This combines basement membrane extract (Matrigel) with biocompatible polymer (poly(ethylene glycol)diacrylate), and a low-toxicity photoinitation system. We achieve rapid (<5 min) photoinduced stiffening over the range of remodelled lung tissue (up to ∼140 kPa). Bronchosphere organoids from primary human bronchial epithelial cells, embedded within the hybrid gel, replicate airway physiology and exhibit a dynamic biological response to matrix stiffening. We show that the expression of mucus proteins MUC5AC and MUC5B is biomechanically enhanced over a period of 24-72 h, with in particular MUC5B showing a substantial response at 48 h after matrix stiffening. Mucus hypersecretion is a symptom of respiratory disease, and these results support the hypothesis that biomechanics is a driver of disease aetiology. We combine the photostiffened hybrid matrix gel with organoids from COPD donors, generating an advanced disease model including both cellular and biomechanical aspects. We propose this technology platform for evaluating mechanomodulatory therapeutics in respiratory disease.

Targeted protein degradation (TPD), a strategy currently used for treating diseases, can selectively degrade specific proteins, thereby circumventing drug resistance. Nevertheless, over 80% of the pathogenic proteins linked to human diseases, including membrane proteins, are not accessible to conventional methods. Aptamers, which are nucleic acid molecules with high affinity and specificity, are chosen from vast libraries of random sequences through in vitro screening techniques. These aptamers can effectively recognize and bind to disease-related membrane proteins, such as those associated with cancer, cardiovascular diseases, and inflammation. Consequently, aptamer-based TPD technology uses these aptamers to deliver target membrane proteins into cells, promoting their degradation and allowing for the specific elimination of pathogenic proteins. This technology showcases significant progress in overcoming the limitations of traditional small molecule inhibitors and in targeting proteins previously considered "undruggable". In this review, we provide an overview of the latest advancements in aptamer-based TPD technology research.

Correction for ‘Artificial testis: a testicular tissue extracellular matrix as a potential bio-ink for 3D printing’ by Zahra Bashiri et al., Biomater. Sci., 2021, 9, 3465–3484, https://doi.org/10.1039/D0BM02209H.

Nanoarchitectured molybdenum oxides (MoO_x) have emerged as promising artificial enzymes, capable of mimicking a broad range of enzymatic activities, including oxidase, peroxidase, catalase, and sulfite oxidase, owing to their unique physicochemical properties such as variable oxidation states, tunable electronic structures, and pH-responsive biodegradability. In addition, MoO_x-based systems demonstrate strong photoresponsiveness, enabling the synergistic integration of enzymatic catalysis with photothermal (PTT) or photodynamic (PDT) therapies under near-infrared (NIR) irradiation. Their excellent biocompatibility and biodegradability further highlight their potential for biomedical applications. This review provides a comprehensive overview of recent advances in the design, synthesis, and bioapplications of MoO_x nanozymes, with an emphasis on their structural versatility and multifunctional therapeutic capabilities. Through strategies such as defect engineering, surface functionalization, and heteroatom doping, the enzyme-mimicking activities of MoO_x nanozymes can be finely tuned, enabling outstanding performance in biosensing, antitumor and antimicrobial therapies, and antioxidation. Finally, the review outlines the prospects and key challenges in translating these innovative nanoplatforms into clinical applications.