Biomaterials Science最新文献

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.

Vaccines have been crucial to dramatic improvements in global health in recent decades, yet next-generation vaccine technologies remain out of reach for much of the world. In particular, there are two overarching global needs: (i) develop vaccines eliciting more potent and durable immune responses, especially to reduce incidence of highly communicable diseases, and (ii) enable simple and cost-efficient formulation to maximize global access. Here, we develop an injectable hydrogel depot technology prepared through physical mixing of commercially available, generally recognized as safe (GRAS) polymers that can be formulated with subunit vaccine components to improve immune responses compared to standard vaccine formulations. We demonstrate that these hydrogels are shear-thinning and rapidly self-healing, enabling facile administration via injection, and they exhibit high yield stresses required for robust in vivo depot formation post-injection. These rheological properties prolong release of subunit vaccine cargo over a period of weeks, both in vitro and in vivo, and synchronize release kinetics across physicochemically distinct vaccine components (antigens and adjuvants). When used for formulation of subunit vaccines against wild-type SARS-CoV-2 and H5N1 influenza, these hydrogels enhance potency and durability of immune responses. This vaccine formulation technology can improve protection against current and potential future pandemic pathogens.

Nanostructured surfaces are increasingly used for cell applications due to their enhanced interactions with numerous cell types; yet, their effects on tissues remain unexplored. To address this limitation, we designed vertical silicon nanopillar (Si-NP) arrays with high density, high aspect ratio and submicrometer diameter, as an optimized geometry based on previous cell-nanostructure studies. Using state-of-the-art in vitro and ex vivo assays, we examined adhesion and biocompatibility of biological samples of different origin and level of complexity -human epithelial-like cell lines, Drosophila imaginal discs and patient-derived lung cancer biopsies-laid on Si-NP arrays or unpatterned flat Si surfaces. Our results demonstrated that Si-NP arrays significantly improved cell and tissue adhesion while preventing oxidative damage and early apoptosis. Consistently, focused ion beam-scanning electron microscopy imaging of cells and tissues showed extended horizontal protrusions and limited vertical wrapping around Si-NP, revealing enhanced cell-NP interactions without cell/tissue penetration. In contrast, flat Si surfaces showed poor adhesion, increased apoptosis, and failed to support tumor biopsy attachment. Interaction with Si-NP arrays upregulated reactive oxygen species (ROS), yet mitochondria-associated ROS remained unchanged, and consequently apoptosis was not induced, indicating that the increased ROS arose from non-mitochondrial compartments and did not compromise viability. Notably, Si-NP arrays matched or outperformed biological responses on tissue culture plastic and Transwell-based assays, which are common in vitro and ex vivo substrates, respectively. These findings provide the first demonstration of the biological suitability of Si-NP arrays for tissue applications in research and clinical translation.

Ovarian cancer (OC) is one of the most fatal malignant tumors of the female reproductive system, and its high recurrence rate in advanced stages and drug resistance severely limit the efficacy of current treatment methods. The molecular mechanisms of drug resistance are complex and remain incompletely understood. Previous studies have attempted to enhance treatment sensitivity by co-delivering antitumor drugs with inhibitors of drug resistance-associated factors. However, these approaches often suffer from inadequate therapeutic efficacy and poor precision due to the inability to precisely control the sequential release of the two agents. To address this, this study designed and constructed a core–shell hydrogel microsphere (MSs) system with both sequential release and magnetothermal synergy functions to effectively intervene in drug-resistant OC. In this system, the shell layer is loaded with the DYRK1B inhibitor AZ191, which is released preferentially to disrupt drug-resistant signaling pathways and sensitize tumor cells. Subsequently, the core layer releases cisplatin to achieve sustained killing of tumor cells. In addition, magnetic nanoparticles embedded in the core can be heated to 42–46 °C under an alternating magnetic field, inducing thermosensitive apoptosis and enhancing cisplatin efficacy. This approach holds promise as a non-invasive alternative to traditional hyperthermic intraperitoneal chemotherapy (HIPEC). In vitro drug release experiments demonstrated that AZ191 exhibited rapid release within the first three hours with a cumulative release of approximately 26%, whereas cisplatin showed minimal early release (∼5%) followed by a markedly accelerated release. In vitro antitumor studies confirmed that the combined chemo-hyperthermia treatment using the core–shell MSs produced the most effective inhibitory effect on drug-resistant OC cells, reducing cell viability to 21% after 48 h, significantly outperforming either chemotherapy or hyperthermia alone. This strategy enables a “resistance-reversal first, precision-killing later” treatment model, offering a novel and effective solution for the treatment of drug-resistant OC.

Malignant tumors pose a serious threat to human health with their high incidence and mortality rates. Although chemotherapeutic agents such as doxorubicin (DOX) exhibit significant antitumor efficacy, their non-specific distribution leads to toxic side effects and mono-chemotherapy fails to achieve complete tumor eradication, significantly limiting clinical applications. This study presents the development and evaluation of a multifunctional nanoplatform, Fe₃O₄@Ce6-DOX@liposome, which integrates magnetic targeting, chemotherapy, and photodynamic therapy (PDT) for enhanced tumor treatment. The nanoparticles (NPs) were engineered to co-deliver the chemotherapeutic drug DOX and the photosensitizer chlorin e6 (Ce6), while superparamagnetic Fe₃O₄ enabled external magnetic guidance. In vitro studies in MCF-7 cells demonstrated the system's light-activated cytotoxicity, with confocal microscopy revealing precise spatiotemporal control over drug release and ROS generation. In vivo evaluation in 4T1 tumor-bearing mice showed that magnetic navigation significantly enhanced tumor accumulation of NPs, leading to 73% tumor growth inhibition through synergistic chemo-PDT effects. The combination of magnetic targeting and dual therapeutic modalities resulted in superior antitumor efficacy compared to individual treatments, with minimal systemic toxicity. These findings highlight the potential of this multifunctional nanoplatform as a precise and effective strategy for solid tumor therapy, offering improved targeting and reduced off-target effects compared to conventional treatments.

Osteoarthritis, as one of the major disabling diseases in the elderly, has a long-term impact on patients’ quality of life and brings heavy medical and social burden. The pathogenesis of osteoarthritis is still unclear, and the main pathological changes include chondrocyte death and osteochondral damage. Therefore, how to solve the cartilage damage caused by osteoarthritis has become the key and difficult point in the clinical treatment of osteoarthritis. Bone marrow mesenchymal stem cells (MSCs) have the potential for self-renewal and multidirectional differentiation, and their engineering has been a hot research topic for the treatment of cartilage damage in recent years. In this study, an injectable hydrogel with stable and continuous release of growth factors was successfully prepared by modifying bone marrow mesenchymal stem cells to overexpress fibroblast growth factor-2 (FGF-2) and piggybacking on a decellularized extracellular matrix (dECM) hydrogel for the repair of cartilage injury in osteoarthritis. This hydrogel demonstrated excellent biocompatibility both in vitro and in vivo. In 3D cell culture, BMSCs in the dECM hydrogel survived, proliferated, and produced abundant cartilage-specific extracellular matrix and growth factors, promoting BMSC differentiation into hyaline chondrocytes. In vitro and in vivo experiments, along with RNA-seq analysis, showed that engineered BMSCs loaded onto the dECM hydrogel could inhibit chondrocyte apoptosis and boost BMSC differentiation. In summary, dECM hydrogels carrying FGF-2 overexpressing bone marrow mesenchymal stem cells have great prospects in accelerating osteochondral defect repair and delaying the progression of osteoarthritis.

Polymer nanodiscs are a research tool that allows membrane proteins (MPs) to be encapsulated by a surrounding amphipathic polymer, isolated and studied to understand their structural and physiological properties. An advantage of using polymer nanodiscs over other membrane mimetics can be found in their ability to natively solubilise membrane proteins (MPs) within an annulus of cellular phospholipids, however, potential polymer interactions with membrane constituents can hinder MP activity making the selection of a suitable polymer critical. This work demonstrates the native solubilisation of G-protein coupled A_2A adenosine receptor (A_2AR) by polymers with alternating units and cationic charge, poly(N-methyl-4-vinyl pyridinium iodide-co-N-alkyl-maleimides) (poly(MVP-co-AlkylMs)), and novel statistical copolymers with pseudozwitterionic charge, poly(potassium 3-sulfopropyl methacrylate-co-2-(trimethyl-amino) ethyl methacrylate-co-n-butyl methacrylate) (poly(KSPMA-co-TMAEMA-co-BMA)), both synthesised using RAFT polymerisation. After surveying a library of polymers within each class, A_2AR extraction was the most efficient using poly(MVP-co-BM) (1 : 1 MVP : BM) and poly(KSPMA-co-TMAEMA-co-BMA) (1 : 1 : 1 KSPMA : TMAEMA : BMA). The optimal pH, temperature, solubilisation time, polymer concentration and ionic strength conditions required for extracting A_2AR were identified and enabled a large-scale A_2AR-nanodisc preparation. The yield of A_2AR-poly(MVP-co-BM) was superior to A_2AR-poly(KSPMA-co-TMAEMA-co-BMA) nanodiscs after affinity purification. Functional assessment of the reconstituted receptors was undertaken using fluorescence correlation spectroscopy (FCS) to determine the ligand binding capacity of A_2AR stabilised within an alternating cationic poly(MVP-co-BM). These native nanodiscs retained their ability to specifically bind A_2AR ligand antagonists.

Monocytes are mononuclear phagocytes crucial for tissue repair, pathogen clearance, and immune surveillance. Comprising 2–10% of all human blood peripheral leukocytes, monocytes are precursors to macrophages and dendritic cells and can be leveraged for diagnostics and treatment of various diseases, such as cancer and autoimmune conditions. Current methods of monocyte isolation for these applications, such as plastic adhesion, magnetic-activated antibody-based selection, and counterflow centrifugal elutriation are limited by either low purity and viability or costly equipment and reagents. Here, we develop and optimize an aptamer-based method for traceless isolation of monocytes from peripheral blood mononuclear cells at low cost with high purity and yield, and with minimal activation and immunogenic risks. We identify and use CD36 as a novel selection marker for monocyte isolation and confirm that monocytes isolated using our CD36-binding aptamer possess similar phenotypes to monocytes isolated from anti-CD14 and anti-CD36 antibodies with higher, unperturbed CD14 and CD36 expression.

Correction for ‘Design considerations for photoinitiator selection in cell-laden gelatin methacryloyl hydrogels’ by Elvan Dogan et al., Biomater. Sci., 2025, https://doi.org/10.1039/d5bm00550g.