Biomaterials Science最新文献

Oral squamous cell carcinoma (OSCC), an aggressive malignancy characterized by high recurrence and metastasis rates, continues to pose a significant clinical challenge to human health. Bacterial immunotherapy has emerged as a promising strategy for cancer treatment by activating multimodal immune responses. Porphyromonas gingivalis (Pg), an oral pathogenic bacterium strongly associated with periodontitis, can produce abundant μ-oxo bisheme on its cell wall (CW) to avoid the oxidative damage induced by H₂O₂ during inflammatory processes. Owing to the presence of μ-oxo bisheme, the CW extracted from Pg (PgCW) exhibits peroxidase (POD)-mimicking activity, as well as sonodynamic therapy (SDT) and chemodynamic therapy (CDT) performances, in addition to its intrinsic immunoadjuvant properties. Herein, PgCW is used as a versatile bacterial therapeutic agent to be loaded within mesoporous TiO₂ grown in situ on dendritic large-pore mesoporous silica nanospheres, thus obtaining a nanomedicine termed DT@PgCW for OSCC combination treatment. Under ultrasound irradiation, DT@PgCW can promote the generation of substantial reactive oxygen species to induce the immunogenic cell death of OSCC cells by multimodal effects, including SDT, CDT, catalyzing the decomposition of H₂O₂ into O₂, and depleting intracellular glutathione. Tumor antigens thus released can further elicit robust immune responses facilitated by the immunoadjuvant action of PgCW, subsequently suppressing OSCC recurrence and metastasis. Altogether, this study develops a versatile bacterial CW-based nanomedicine and provides an effective strategy for OSCC combination treatment.

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.

Incorporating micelles into polymeric hydrogels offers a powerful route to combine the tuneable mechanical and structural properties of hydrogels with the precise drug-loading and release capabilities of nanocarriers. However, the method of micelle incorporation and its influence on hydrogel performance have yet to be studied in detail. Here, we present a modular strategy to tailor gelatin-norbornene hydrogels by integrating Pluronic® F127 micelles either physically or via covalent incorporation using norbornene-functionalised Pluronic (Pl_Nb). Pl_Nb was synthesised via Steglich esterification with >95% terminal functionalisation, forming stable, thermo-responsive micelles (2.5–15% w/v) with doxorubicin encapsulation efficiency of ∼80%, comparable to unmodified Pluronic. Micelles were either physically entrapped or chemically integrated into gelatin-norbornene networks via bioorthogonal thiol–ene crosslinking. The incorporation route dictated network mechanics and dynamics: chemical crosslinking conferred temperature-dependent behaviour and enhanced stress relaxation compared to physical crosslinking, whereas both incorporation routes reduced stiffness relative to neat hydrogels and slowed drug release compared to direct loading. All hydrogels were cytocompatible, and the released doxorubicin retained its bioactivity, reducing cancer cell viability. These findings establish micelle–hydrogel coupling as a versatile design approach for engineering biomaterials with potential in controlled therapeutic delivery and regenerative medicine.

In this work, the use of droplet microreactors is demonstrated for the on-demand synthesis of three calcium phosphate minerals. In a simple three-inlet, flow focusing design, microdroplets serve as isolated reactors where crystals are formed under controlled conditions. Selective production of brushite, hydroxyapatite, or fluorapatite was achieved by modulating only the composition and the pH of a buffer stream without disturbing the flow regime and the continuous operation of the system. Temperature and residence time have been proved as key variables to control the properties of the resulted particles. Moving from 25 to 37 °C resulted in a more crystalline material, while by increasing the residence time from 2 to 10 min, bigger particles were obtained. Compared to the standard batch synthesis, in microfluidics, crystallisation crystals were less aggregated and smaller in size. During μ-LIF measurements, it was confirmed that the formation of the crystals affects the mixing quality within the droplets and this can be a field of improvement in order to get particles with more consistent properties. Overall, this work shows the potential of droplet microreactors as a versatile “factory-on-chip” tool for continuous production of biomaterials. Beyond calcium phosphates, the same approach provides a scalable route to precision synthesis of multiphase and composite materials, enabling new frontiers in biomedical translation and advanced manufacturing.

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.

Osteomyelitis, a severe bone infection, poses significant challenges due to antibiotic resistance and limited efficacy of conventional treatments, which often rely on non-degradable carriers with burst antibiotic release. Biodegradable scaffolds with intrinsic antimicrobial functionality offer a promising alternative combining structural support, sustained therapy, and bone tissue regeneration. In this study, novel hydrophobic derivatives of the antibiotic ciprofloxacin-allylciprofloxacin (Cpf-Allyl) and vinylbenzylciprofloxacin (Cpf-VBC) – were synthesized and evaluated as photoinitiators for one- and two-photon polymerization (1PP and 2PP) of star-shaped polylactide (SS-PLA) to obtain scaffolds designed for bone regeneration. Both derivatives retained antimicrobial activity comparable to unmodified ciprofloxacin against key pathogens, including S. aureus and E. coli. Cpf-VBC demonstrated favorable photophysical properties for 2PP: 40% higher absorbance at 263 nm and lower fluorescence quantum yield (8% vs. 10% for Cpf-Allyl), approaching the efficiency of the commercial photoinitiator Bis-b. All photosensitive resins achieved high degrees of conversion (DC ≥ 60%) for the 1PP-method. In contrast, Cpf-VBC-based 2PP scaffolds showed a significantly lower DC (29 ± 4%) compared to both Cpf-Allyl-based and Bis-b-based scaffolds (∼58%). However, the use of Cpf-VBC resulted in increased surface hydrophilicity of the scaffolds, as evidenced by lower water contact angles (62 ± 2°) and a higher polar component of surface energy. All fabricated scaffolds promoted the proliferation of mesenchymal stromal cells and their efficient osteogenic differentiation supported by scaffold mineralization. The scaffolds exhibited topographical and mechanical properties suitable for bone tissue engineering, with a Young's modulus (262–377 MPa) in the range of human cancellous bone.

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.

Bone is a dynamic tissue that responds to mechanical forces and possesses intrinsic mechanoelectrical activity. Recently, electrically conductive polymers have emerged as stimulating biomaterials for bone tissue engineering. However, the effect of conductive scaffolds under mechanical stimulation towards bone formation remains unclear. This study presents the development of electrically conductive, mechanoactive porous scaffolds, and the validation of their osteogenic capacity under mechanical stimulation. The developed scaffolds contain poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) into a double polymeric network comprising poly(vinyl alcohol) (PVA) and gelatin (Gel). PEDOT-containing scaffolds demonstrated superior electrical conductivity, increased surface porosity, and an elevated Young modulus of 2.7 ± 0.4 MPa compared to the PVA/Gel control. Pre-osteoblastic cells cultured within the conductive, mechanoactive scaffolds under uniaxial compression showed increased cell viability, calcium influx, and upregulation of osteogenic markers. Mechanical loading enhanced the activation of the mechanotransduction markers YAP/TAZ, upregulated alkaline phosphatase activity, collagen secretion, and calcium deposition, particularly in PEDOT-containing scaffolds, with hydroxyapatite formation on day 21. In vivo subcutaneous implantation of the developed scaffolds indicated lack of any adverse immune responses. These results highlight the great potential of the developed electroactive, mechanoresponsive scaffolds as biomimetic substrates to enhance osteogenesis under mechanical stimulation.

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.