Biomaterials Science最新文献

Infections triggered by bacteria in diabetic wounds continue to pose a significant challenge, primarily due to the inflammatory microenvironment induced by high glucose levels, which favor bacterial growth. Hence, developing dressings tailored for diabetic wound treatment has become particularly crucial. Here, we prepared a composite hydrogel derived from natural polymers as a wound dressing. This composite hydrogel was fabricated by the cross-linking of hyaluronic acid (HA) grafted with chlorogenic acid (CA) and phenylboronic acid (PBA) and the incorporation of copper sulfide nanoparticles (CuS NPs). The hydrogels exhibited adequate adhesive properties and self-healing capabilities. By releasing the natural polyphenol CA, the hydrogel showed promising antioxidant performance, excellent promotion of cell proliferation, and angiogenesis properties, thereby effectively promoting tissue repair. The treatment on an in vivo diabetes wound model indicated that the dressing contributed to wound closure, re-epithelialization, collagen deposition, and the downregulation of inflammatory factors. This multifunctional hydrogel presented a potent strategy for managing infected diabetic wounds and showed significant promise for clinical translation.

The development of effective vaccines against tumor-associated MUC1 (taMUC1) glycopeptide antigens remains a significant challenge due to their poor intrinsic immunogenicity. A key limitation in conjugate vaccine design lies in the structural alterations that occur upon carrier protein functionalization, which can reduce the accessibility of surface-conjugated antigens, ultimately compromising antigen presentation. In this study, we present a semi-synthetic vaccine platform in which taMUC1 glycopeptides are displayed on synthetic cyclopeptide scaffolds—configured either as monovalent or clustered tetravalent platforms—and subsequently grafted onto solvent-exposed amine residues of the CRM₁₉₇ protein via squaramide linkages. These conjugates were purified under denaturing conditions via reverse phase HPLC and evaluated in vivo through mouse immunization studies. Despite differences in antigen valency and glycopeptide loading per protein, both conjugates induced comparable levels of antigen-specific IgGs and CD4⁺/CD8⁺ T-cell activation when co-administered with the QS-21 adjuvant. Notably, although antibody titers were similar, post-immunization sera from mice immunized with the tetravalent conjugate plus the QS-21 adjuvant showed enhanced reactivity toward native taMUC1 expressed on MCF7 cancer cells, suggesting improved epitope recognition. These results highlight the impact of scaffold design, antigen display and adjuvantation on vaccine efficacy and establish a promising platform for the development of conjugate vaccines targeting weak tumor-associated antigens.

Polymer conjugation is a common strategy to improve the pharmacokinetics of aptamers, yet its effects on aptamer properties are incompletely understood. Poly(ethylene glycol) (PEG) is the most widely used polymer for this purpose, but concerns about anti-PEG immune responses have prompted interest in alternative polymers. We previously reported that conjugation with the zwitterionic polymer poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) significantly prolongs the circulation time of a DNA aptamer while avoiding anti-PEG antibody recognition. In this study, we evaluated the physicochemical and functional consequences of PMPC conjugation of aptamers. Biophysical analyses suggested that the secondary structure and target-binding affinity of the aptamer were preserved, while functional consequences upon PMPC conjugation varied with the targets. The activity of a membrane receptor-targeting aptamer partially decreased, likely due to spatial constraints around the cell membrane, while RB005, targeting soluble activated coagulation factor IX, retained its full activity. In addition, PMPC conjugation significantly prolonged the in vivo plasma retention of RB005. By elucidating the effects of PMPC on aptamer properties and introducing another example that further supports the general applicability of PMPC conjugation in enhancing aptamer pharmacokinetics, these findings support PMPC as a promising alternative to PEG.

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.

Diabetic wound healing has long been plagued by a series of complex problems caused by the pathological environment of high glucose, such as ischemia, hypoxia, and inflammatory responses. In order to solve this dilemma, we developed a new gel preparation with both green natural characteristics and excellent biological activity, aiming to provide an efficient and safe solution for diabetic wound healing. The gel uses microalgae as the core carrier, and it also plays an important role as an oxygen supply source. Through covalent bonding, the functional component concanavalin A and PEG-modified gold nanoparticles (PEG-AuNPs) were efficiently loaded on the polymer, which ensured the stable existence and controlled release of the components. Subsequently, the composite system was incorporated into the pre-gel fluid of the photocrosslinked methacryloylated gelatin to obtain our designed gel composite. On the one hand, the microalgae present in the material can continuously produce oxygen driven by light, effectively improve the local hypoxic microenvironment of the wound, and provide sufficient oxygen for cell proliferation and tissue repair. On the other hand, concanavalin A can specifically bind to glucose, and then cooperate with AuNPs with glucose oxidase activity to exert an efficient local hypoglycemic effect, thereby alleviating the adverse effects of high glucose on healing from the root. Through systematic experimental verification, this study confirmed the application prospects of this biocomposite material with multiple pro-healing properties in the field of diabetic wound management.

Gelatin dissolvable microneedle (DMN) patches offer a promising, painless, and rapid transdermal delivery platform. However, conventional DMNs with <5% w/v gelatin exhibit poor mechanical strength and storage stability of biomolecules, while higher concentrations (>5% w/v) hinder dissolvability due to gelation. To address this, we introduced a tailored number of carboxylic groups into the gelatin backbone, generating Modified Gelatin (MG) with improved solubility and reduced viscosity by limiting intra- and intermolecular interactions. MG-DMNs fabricated from MG at a concentration of 10%–20% w/v and ≥5% w/v stabilizing molecules (e.g., trehalose) exhibited rapid dissolution (5 minutes), high mechanical strength (>95 N per patch), and excellent storage stability. Notably, MG-DMNs retained >80% of platelet-rich plasma (PRP) activity after one month of storage at 4 °C and 25 °C, and ∼60% at 40 °C under 75% relative humidity, as confirmed through an in vitro bioassay, an in ovo CAM assay, and in vivo diabetic wound healing studies. MG-DMNs enable the cold-chain-free and stable delivery of biomolecules for biomedical applications.

While transnasal nanoparticle (NP) mucosal uptake is well-documented, recent studies suggest that some NPs and viruses can also enter the central nervous system (CNS) through systemic circulation without disrupting blood–brain barrier (BBB) integrity. Here, we used T₁-weighted MRI, ICP-AES analysis and optical tomography to track the distribution of 50 nm Mn₃O₄-NPs and 130 nm polyelectrolyte layer-by-layer capsules labeled with Cy7 and gold NPs (LbL-Au) in mouse brains following intravenous or intranasal administration. The olfactory epithelium (OE) served as a critical gateway for blood-to-brain NP transport, mediating CNS entry through distinct intracellular and paracellular pathways. Pharmacological inhibition of axonal transport (colchicine, 10 μg μl⁻¹) and chemical ablation of the OE (ZnCl₂, 5%) completely blocked Mn₃O₄-NP accumulation in olfactory pathways (olfactory bulb, olfactory tract, and cortical targets), while permitting unaltered deposition in the adenohypophysis, confirming an olfactory neuron-dependent transport mechanism. In contrast, LbL-Au translocation was abolished by epithelial ablation but unaffected by axonal transport inhibition, demonstrating predominant paracellular passage. Notably, both intranasal and intravenous administration routes resulted in NP deposition within the OE and subsequent brain delivery, revealing route-independent olfactory uptake. These findings establish the OE as a dual-pathway hub for systemic NPs, facilitating CNS entry via intracellular axonal transport (Mn₃O₄-NPs) or paracellular mechanisms (LbL-Au). By demonstrating that blood-borne NPs can exploit olfactory pathways to bypass the BBB, this work challenges traditional models of CNS xenobiotic entry and opens new avenues for targeted neurotherapeutic delivery.

Atopic dermatitis is a typical chronic inflammatory disease with pathological characteristics of persistent immune activation and oxidative stress. Combined anti-inflammatory and antioxidant treatment can effectively block the inflammatory cascade while reducing oxidative damage. Halloysite nanotubes (HNTs) are the main components of the traditional Chinese medicine “Chishizhi”, which shows the medicinal functions of hemostasis and astringency. However, the efficacy of HNTs alone in treating diseases is relatively weak, and their therapeutic effect can be improved by surface modification and drug loading. Herein, CuO–Fe₃O₄ nanoparticles were synthesized on the outer surfaces of HNTs by a hydrothermal reaction. CuO–Fe₃O₄@HNTs have high SOD and CAT enzyme activities under neutral conditions. Then, the nanozyme-modified HNT powder was prepared into sprayable hydrogels by introduction of sodium alginate (SA) and aloe vera extracts. Cell experiments confirmed that the hydrogel can promote HacaT cell proliferation within 0–200 μg mL⁻¹ concentration. Through the mouse dermatitis model, it was seen that a CuO–Fe₃O₄@HNTs–SA composite hydrogel has a good therapeutic effect on atopic dermatitis. Compared with the positive drug halcinonide solution, the CuO–Fe₃O₄ nanozyme-incorporated hydrogel showed an enhanced therapeutic effect, which shows promising prospects for the clinical treatment of atopic dermatitis.

Ferroptosis, a regulated cell death pathway characterized by iron dysregulation and lipid peroxide accumulation, has emerged as a pivotal target in the treatment of cancer and other diseases. As a natural iron storage protein in organisms, ferritin (Fn) is involved in regulating intracellular iron homeostasis through processes such as iron transport, storage, and ferritinophagy, which in turn significantly influence the Fenton reaction, making it closely related to the occurrence of ferroptosis. Additionally, due to the unique cavity structure of ferritin nanocages, their excellent biocompatibility and their specific binding ability for the highly expressed transferrin receptor 1 (TfR1) on the surface of tumor cells, ferritin nanocages have been extensively explored in the design and development of drug delivery systems (DDS). Given the above background, this paper reviews the novel mechanisms of ferroptosis and the research advancements in the related diseases and drugs. It further explores the structure and application of ferritin (including DDS design and vaccine development) and emphasizes the construction of DDSs regulating ferroptosis through utilizing ferritin nanocages as carriers or by targeting the disruption of endogenous ferritin, with the expectation of providing a reference for the development of safer and more effective nanoformulations.

Cancer immunotherapy has attracted tremendous attention. To improve the response rate of immune checkpoint inhibitors and tumor antigens in immunosuppressive cancer, the induction of piezoelectric-triggered cancer cell death can increase antigenicity. Herein, we construct a piezoelectric poly(vinyl alcohol) (PVA)/polyvinylidene fluoride (PVDF)/MXene hydrogel loaded with a biomimetic cancer cell membrane (CCM) that incorporates TLR7/8a/anti-PD-L1. The CCM surface proteins act as tumor-specific antigens. Poly(lactic-co-glycolic acid) (PLGA) is used to enhance the stability and attachment of the MXene. After adding the MXene, the hydrogel exhibits a higher piezoelectric coefficient, greater electrical signal yield with superior stability, and excellent mechanical strength. Ultrasound (US) enhances the piezoelectric effect of the PVA/PVDF/MXene-CCM hydrogel. This is confirmed through in vitro reduction and oxidation catalysis reactions. The US-stimulated electrical signal inhibits cancer cells via apoptosis induction, endoplasmic stress, and mitochondrial membrane depolarization. It leads to the secretion of danger-associated molecular patterns into the cytoplasm, which promotes dendritic cell maturation and cytotoxic T-lymphocyte infiltration, thereby reversing the immunosuppressive tumor microenvironment. In vivo studies show that the hydrogel offers great therapeutic efficacy to control tumor growth due to the combined effects of the piezoelectric effect and immune checkpoint blockade (ICB) therapy. It improves dendritic cell maturation and increases cytotoxic T-cells. Therefore, our work presents a novel piezoelectric hydrogel and new therapeutic strategies with great potential and versatility for treating breast cancers.