Biomaterials Science最新文献

The targeted detection of cancer cells is crucial for tumour diagnosis and therapeutic treatment. Recently, luminescent carbon dots have generated wide interest in biomedical applications, thanks to their unique properties such as biocompatibility, tuneable emission, water solubility and the possibility of surface functionalization. Herein, we report the conjugation of red emitting carbon dots (RCDs) to alginate and the sTN58 aptamer to obtain systems able to selectively recognize cancer cells that can be exploited in bioimaging and potentially as photothermal agents.

Bacterial membrane vesicles (MVs) are a heterogeneous group of lipid-bound structures produced by bacteria. Antibiotic stress aggravates the secretion of MVs that contributes to the development of bacterial antibiotic resistance. This review provides a focused, resistance-oriented perspective on the interplay between MVs and antibiotic resistance. We outline MV biogenesis, emphasizing the distinct formation mechanisms of Gram-negative and Gram-positive bacteria. We further focus on the secretion of MVs under antibiotic stress, highlighting pathways such as bacterial envelope stress, SOS response, and cell wall disruption. The pivotal role of MVs in bacterial antibiotic resistance is also elucidated, including neutralizing antibiotics, absorbing phages, and facilitating drug efflux, biofilm formation, and horizontal gene transfer. Current challenges and future prospects for elucidating MV-mediated mechanisms in antibiotic resistance are discussed.

Currently, single-target therapy and difficulty in brain drug delivery gravely impede the treatment of Alzheimer's disease (AD). The promising development of microRNA-124-3p (miR-124-3p) serves as a possibility for multiple therapeutic approaches for AD. However, the effective delivery of miR-124-3p to AD-affected brain regions remains a major challenge, primarily due to the blood-brain barrier (BBB) and the inherent instability of therapeutic miR-124-3p. Herein, we engineered miR-124-3p-enriched microglial exosomes (Exo-124-3p) as a biomimetic nanomedicine for the multifunctional treatment of AD. Exo-124-3p can traverse the BBB and facilitate activated-microglia targeting. Subsequently, the on-demand release of miR-124-3p from Exo-124-3p decreased the aggregation of β-amyloid (Aβ) plaques, attenuated the activation of microglia/astrocytes, and exhibited a valuable neuroprotective effect, thereby remolding the AD focal microenvironment. Notably, the in vivo results demonstrated that Exo-124-3p significantly improved the cognitive function in an AD mouse model. Mechanistically, it was elucidated that Exo-124-3p can bind to the 3′UTR region of MEKK3, ultimately inhibiting the MEKK3/NF-κB signaling pathway, thereby ameliorating AD neuroinflammation. Consequently, this study not only provides a promising therapeutic approach for AD combinational therapy, but also advances the development of miRNA delivery in other brain diseases.

Cancer is the second most common cause of death worldwide, with its origin in cells abnormal growth. Available chemotherapeutics present major drawbacks, usually associated with high toxicity and poor distribution, with only a small fraction of the drug reaching the tumour site. Nanoparticles, particularly dendrimers, are paving the way to the front line of cancer treatment, primarily for drug and gene delivery, diagnosis, and disease monitoring. In the present work, we demonstrate the intrinsic anticancer activity of two polycationic core–shell PURE biodendrimers, PURE_G4-OEI₄₈ and PURE_G4-OCEI₂₄, designed as synthetic mimics of anticancer peptides (SMACPs), and evaluate their action against several cancer cell lines. Our findings show that PURE_G4-OEI₄₈ disrupts cell membrane integrity, interacts with mitochondria, and induces cell death by promoting apoptosis, as indicated by Annexin V⁺/PI⁺ cells when incubated with the IC₅₀ concentration. PURE_G4-OCEI₂₄, which is more hydrophobic and less cationic than PURE_G4-OEI₄₈, exhibits cytotoxic effects on cancer cells and inhibits wound healing after 24 hours, and its mechanism of action may be partially associated with cell necrosis. Based on our results, we conclude that both core–shell polycationic PURE dendrimers target the mitochondrial membrane, activating distinct cell death mechanisms.

Cartilage injuries present a significant clinical burden due to the tissue's limited regenerative capacity. Microfracture (Mfx) remains the gold standard of cartilage repair but often results in inadequate defect fill and inferior tissue formation. Point-of-care augmentations to the Mfx environment represent implementable and cost-effective methods to enhance outcomes. The objective of this study was to evaluate platelet lysate (PL) as an adjuvant to microfracture-based cartilage repair, with the goal of maintaining tissue volume and promoting functional repair. The impact of PL on the activity of marrow-derived cells (MDCs) was first evaluated in monolayer culture, which demonstrated an increase in cellular area and proliferation. Next, PL was incorporated into fibrin gels (to mimic fibrin-rich Mfx), and MDCs encapsulated within PL-containing fibrin gels exhibited increased proliferation, increased cellular area, and reduced fibrosis markers. PL incorporation into fibrin gels led to clear changes to initial nanostructure and an increase in initial mechanical properties, which resulted in less MDC-mediated contraction during culture. These findings suggested that time-zero augmentation of Mfx with PL may alter both cellular signaling and Mfx clot structure/remodeling. Finally, PL-augmented Mfx was evaluated in a pig trochlear osteochondral defect model (t = 5 weeks). While PL-treated defects exhibited reduced contraction and improved macroscopic appearance over Mfx alone, micro-CT and mechanical testing revealed no significant differences in subchondral bone remodeling or repair tissue stiffness. Histological analysis and grading showed no significant improvements in cartilage repair quality across treatment groups, suggesting that while PL may influence early clot stability, its effects on long-term tissue maturation remain uncertain. “Future studies are needed to determine whether PL-based augmentation provides sustained functional benefits, potentially in combination with additional biological or mechanical strategies”.

The discovery of exosomes in the early 1980s transformed modern medicine by establishing a new class of cell-free therapeutics. Exosomes, which are classified as diminutive membrane-bound vesicles, are secreted by all cell types in the extracellular space. Functionally, they are involved in intercellular communication and transport bioactive cargoes across the cells. Recently, exosomes have gained attention for their potential in the treatment and diagnosis of osteoarthritis (OA). Stem cell-derived exosomes are known to promote cartilage regeneration and reduce inflammation, while endogenous exosomes from osteoarthritic cells exacerbate the progression of OA. Despite their therapeutic potential, the low retention of exosomes administered intra-articularly in the joint cavity limits their application. Hydrogels, as a delivery vehicle for exosomes, allow them to achieve an increased residence time and sustained and localized release within the osteoarthritic joint. Furthermore, hydrogels protect exosomes from enzymatic degradation, mimic the extracellular matrix, and enhance their bioavailability and regenerative potential. This review provides an overview of the biogenesis of exosomes and key techniques for exosome isolation and characterization. We also discuss their functional role in therapy and the pathogenesis of OA. Additionally, we highlight the diagnostic value of exosomal miRNAs, lncRNAs, and circRNAs as emerging biomarkers for OA. Furthermore, we spotlight recent research in developing exosome-loaded hydrogels for OA treatment, focusing on their therapeutic outcomes, encapsulation, and characterization. Finally, we discuss current difficulties and prospects for translating exosome-loaded hydrogels into clinical settings.

Anastomotic leaks are among the most severe side effects following abdominal surgeries. Conventional surgical sealants and emerging hydrogel adhesives often lose mechanical and adhesion strength when exposed to leaked digestive enzymes. Here, we report a tannin-encapsulating tough hydrogel adhesive that exhibits enhanced mechanical and adhesive properties upon the encounter of leaked proteins. The hydrogel is composed of a gelatin–acrylate crosslinked network with encapsulated tannin and can adhere to a wet surface via amine–carboxyl chemistry. In the context of anastomotic leaks, tannin within the hydrogel can form a complex with proteins including the digestive enzymes, leading to increased gel stiffness and storage modulus. The enhanced mechanical strength confers improved adhesive properties on the hydrogel adhesive. Additionally, the tannin-bearing hydrogel adhesive shows excellent antibacterial properties. This adaptive and antibacterial hydrogel adhesive provides a promising sealant for gastrointestinal surgery and other applications.

The delayed healing of alveolar bone defects caused by periodontitis remains a thorny problem. Here, we developed a kind of natural hydrogel, Cu/Zn-FG, synthesized based on the formation of a hydrogel network triggered by thrombin and the coordination bond between the fibrin and metal ions. The characteristics of Cu/Zn-FG were evaluated using the following methods: morphological observation, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). The anti-inflammatory effect and osteogenic differentiation potential of Cu/Zn-FG were also assessed on the RAW264.7 and MC3T3-E1 cells. Moreover, Cu/Zn-FG's in vivo therapeutic efficacy was evaluated in a rat model of periodontitis. The results demonstrated that Cu/Zn-FG could release copper and zinc ions for 26 hours as the protease activity increases in the infection microenvironment, and these ions can maintain their biological activity in vitro. Furthermore, we found that Cu/Zn-FG can effectively inhibit the growth activity of Porphyromonas gingivalis (P. gingivalis), promote osteogenic differentiation of MC3T3-E1 and regulate the expression of inflammatory factors of RAW264.7. In the process of the in vivo experiment, periodontitis rats treated with Cu/Zn-FG revealed that bone regeneration was accelerated. Our study confirms that Cu/Zn-FG is an innovative material that could promote alveolar bone regeneration in a rat model of periodontitis, exhibiting its translational potential for clinical application and providing a new therapeutic strategy in the treatment of periodontitis.

The escalating prevalence of drug-resistant microbes coupled with their persistence in mono- and polymicrobial biofilms impose a critical healthcare challenge. Metal nanoparticles, particularly silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs), offer potent antimicrobial activity but face limitations due to their complex synthetic protocols, reliance on external reducing agents and surfactants, resulting compromised biocompatibility and poor in vivo outcomes. Herein, we present a facile, biocompatible approach for synthesizing antimicrobial supramolecular nanocomposite hydrogels (ASNH) via a one-pot, aqueous process that enables in situ growth of AgNPs and AuNPs through supramolecular interactions with short peptides. Utilizing sunlight photoirradiation, these hydrogels eliminate external reducing agents while serving as stabilizers for nanoparticle formation. The metallohydrogels exhibit rapid and broad-spectrum antimicrobial activity, against multidrug resistant bacteria and fungi. In addition to disrupting single species biofilms, the optimal hydrogels significantly eradicate polymicrobial biofilms formed by MRSA and Candida albicans. The hydrogels achieve ≥1.5-log reduction in microbial viability, outperforming last resort antibiotics and commercial silver-based ointments. In vivo studies demonstrate accelerated wound healing by reducing bacterial burden and mitigating inflammatory responses, while enhancing neovascularization, granulation, fibroblast proliferation, collagen deposition and epithelialization. The mild, economical synthesis and robust antimicrobial efficacy of these peptide-based metallohydrogels underscore their clinical potential as next-generation biomaterials for polymicrobial biofilm-associated infections.

Dyes exhibiting polarity-dependent color changes, known as solvatochromism, have great potential for creating sensors, smart materials, and responsive coatings. However, full-range color shifts require a technique to disperse dyes across a wide range of solvent polarities, which remains a persistent challenge. For example, hydrophobic dyes often aggregate in water, preventing effective color shifts. Although surfactants can assist in dye dispersion, they can also prevent solvent molecules from accessing the dye. To address this, we used a 60-mer protein nanocage, TIP60, with a densely pyrene-modified interior surface. The modification did not induce protein denaturation, as monitored by small-angle X-ray scattering, and greatly increased the aqueous solubility of a hydrophobic solvatochromic dye, Nile Red (NR), while preserving its fluorescence. The NR-loaded solution appeared blue, reflecting the polar environment surrounding NR. Cryogenic electron microscopy suggested that the pyrenes interacted with each other to form a binding site for NR. This interaction also contributed to thermostability of TIP60 (65 °C to 86 °C) and stability against sodium dodecyl sulfate, as observed by electrophoresis experiments. When brushed onto plain copy paper, the NR-loaded nanocage appeared bluish-purple and shifted reversibly to purplish red upon heating, returning on cooling—presumably via nanocage dissociation and reassembly. The color change was also sensitive to humidity. We term this material “misteINK”, a protein-based ink with reversible temperature- and humidity-dependent color changes. These findings demonstrate that a single-step interior modification enables the rational design of protein materials for tuning dye photophysics, providing a powerful strategy for designing protein-based functional materials.