Biomedical materials (Bristol, England)最新文献

Mesoporous silica nanoparticles (MSNs) have been demonstrated to promote osteoblast differentiation; however, the unclear impact of their surface roughness on osteogenesis, coupled with inadequate targeting capability and suboptimal therapeutic outcomes, presents major challenges. Herein, we developed a biomimetic nanoplatform, CM@DEX-R-MSN, by coating dexamethasone (DEX) loaded-rough MSN (R-MSN) with mesenchymal stem cell (MSC) membranes (CM) to enhance osteogenic differentiation of MSCs for improved bone regeneration. The CM@DEX-R-MSN showed retained rough surfaces with a hydrodynamic diameter of 164.35 ± 5.81 nm, a Zeta potential of -11.98 ± 1.37 mV with good MSC membrane integrity, negligible cytotoxicity bothin vitroandin vivo. CM@DEX-R-MSN exhibited significantly enhanced MSC internalization compared to uncoated MSN. They markedly upregulated alkaline phosphatase activity, osteogenic markers, and mineralization nodule formationin vitro. In bone defect model established in rabbits, CM@DEX-R-MSN restored bone volume and prolonged retention at the defect site. More importantly, we experimentally observed that both R-MSN and CM-coated nanoparticles exhibited superior osteogenic differentiation effects compared to conventional MSNs and non-coated counterparts, respectively-with CM@DEX-R-MSN demonstrating the most potent efficacy. Our results demonstrated that CM@DEX-R-MSN synergistically integrates MSC membrane-mediated homotypic targeting, nanotopography of R-MSN, and DEX-driven osteogenic differentiation, offering a promising targeted therapeutic strategy for bone regeneration. Their enhanced biocompatibility, osteogenic efficacy, and sustained retention underscore its translational potential for orthopedic applications.

Bone morphogenetic protein-2 (BMP-2) is a highly potent osteoinductive factor that has received approval from the U.S. Food and Drug Administration due to its significant osteogenic properties. Nonetheless, its clinical utility is limited by adverse effects linked to supraphysiological dosing and its brief half-life. Consequently, there is a pressing need for a safe and effective delivery system to enable the sustained release of BMP-2. In this study, we have developed bilayer-structured oxidized sodium alginate-carboxymethyl chitosan (OAC) microspheres through the application of electrospraying and the Schiff reaction. The inner layer, composed of oxidized sodium alginate, electrostatically adsorbs BMP-2, while the porous polyelectrolyte membrane on the surface enhances adsorption, thereby effectively regulating the prolonged and controlled release of BMP-2. We assessed the minimal osteogenic induction concentration of BMP-2 on rat bone marrow mesenchymal stem cells (rBMSCs) to optimize the BMP-2 loading concentration within the microspheres.In vitroexperiments demonstrated that the bilayer membrane structure of the hydrogel microspheres significantly delayed the release of BMP-2, facilitating a long-term, sustained release. Furthermore, the microspheres facilitated the proliferation, migration, and osteogenic differentiation of rBMSCs. The osteogenic-promoting efficacy of the BMP-2-encapsulated OAC microspheres was further corroboratedin vivothrough implantation alongside calcium phosphate cement into the dorsal region of nude mice. Collectively, the BMP-2-encapsulated OAC microspheres we developed constitute a promising clinical approach to augment scaffold degradation and osteogenesis for the repair of bone defects.

Endothelialisation is critical for the success of coronary stents, as it mitigates thrombosis risk and ensures long-term vascular healing. While advancements in stent materials, surface modifications and surface coatings have improved stent performance, the influence of stent cell geometry (particularly cell shape and size) on endothelialisation remains underexplored. This review examines the principles of cell growth influenced by geometry, drawing insights from non-coronary stent applications to identify research gaps in coronary stent applications. While recent studies highlight the role of surface microstructure in endothelialisation, the impact of stent cell geometry remains largely unexplored. Moreover, insights from tissue engineering suggest that optimising scaffold geometry could enhance endothelial cells (ECs) adhesion and proliferation, thereby accelerating re-endothelialisation. Based on these considerations, this review hypothesizes that optimising stent cell geometry could directly regulate ECs behaviour, thereby influencing endothelialisation performance. Finally, this paper critically evaluates the limitations of existing research and proposes future directions for leveraging cell geometry in the development of next-generation stents with improved biocompatibility and endothelialisation performance.

ZnO-doped hydroxyapatite (HAp) coatings were developed on thermally sensitive polyetheretherketone (PEEK) substrates using a hybrid plasma spraying approach that combines powder and solution precursor feedstocks. Three coating architectures with different ZnO contents were designed to assess the influence of zinc incorporation on antibacterial and osteogenic performance. All coatings were deposited at a low plasma power (5.7 kW), enabling successful deposition without thermal degradation of the PEEK substrate, and achieving bond strengths up to 17 MPa. ZnO-doped coatings exhibited antibacterial activity againstE. coliandS. aureus, with significantly higher efficacy againstE. coli. In vitrotests using MC3T3-E1 pre-osteoblasts showed enhanced cytocompatibility and osteogenic differentiation at low ZnO concentrations, as indicated by increased alkaline phosphatase (ALP) activity and calcium deposition exceeding those of undoped HAp coatings by over 50% after 21 d. The combination of antimicrobial and osteoinductive properties suggests that ZnO-doped HAp coatings are promising candidates for PEEK-based orthopedic implants.

Sonodynamic therapy (SDT) is a viable alternative to traditional photodynamic therapy owing to its ability to penetrate tissue. However, the therapeutic efficacy of a single SDT treatment is constrained by the prolonged hypoxia of the tumor, rendering SDT ineffective for treating disease. SDT was used in conjunction with nitric oxide (NO) gas in this study to induce apoptosis and ferroptosis in hepatocellular carcinoma (HCC) cells for treating cancer treatment. We synthesized 5,10,15,20-tetra (4-aminophenyl) porphyrin nanobubbles (TAPP@NBs) for the SDT treatment. S-nitroso glutathione (GSNO) was used as an NO gas donor. Thein vitroanticancer effect of the combined treatment was examined using HepG2 and HUH7 hepatoma cell lines. Reactive oxygen species and NO were examined using 2,7-dichlorodihydrofluorescein diacetate and 3-amino,4-aminomethyl-2',7'-difluorescein diacetate staining, respectively. Cell proliferation and apoptosis were analyzed using CCK-8 and flow cytometry, respectively. Ferroptosis was evidenced using glutathione and malondialdehyde assays. The cellular migratory capacity was assessed using a Transwell assay. TAPP@NBs can serve as a sonosensitizer for the SDT. GSNO serves as an NO donor under ultrasound and contributes to gas treatment, considerably increasing SDT efficacy. HCC cell proliferation and migration were considerably lower after combined SDT and NO gas therapy. Combined SDT and NO gas therapy induced apoptosis and ferroptosis in HCC cells. This paper describes a novel approach for optimizing tumor treatment.

A key challenge in bone tissue engineering (BTE) is designing structurally supportive scaffolds, mimicking the native bone matrix, yet also highly porous to allow nutrient diffusion, cell infiltration, and proliferation. This study investigated the effect of scaffold interconnectivity on human bone marrow stromal cell (BMSC) behaviour. Highly interconnected, porous scaffolds (polyHIPEs) were fabricated using the emulsion templating method from 2-ethylhexyl acrylate/isobornyl acrylate (IBOA) and stabilised with ∼200 nm IBOA particles. Pore interconnectivity was tuned by varying the internal phase fraction from 75%-85% and characterised by the degree of openness, Euler number, frequency, and size of pore interconnects. The attachment, proliferation, infiltration, and osteogenic differentiation of the BMSC cell line (Y201) were evaluated on these scaffolds. Results showed that high pore interconnectivity facilitated diffusion and cell infiltration throughout the scaffolds. Furthermore, the most interconnected scaffolds enhanced osteogenic differentiation of Y201 cells, as evidenced by elevated alkaline phosphatase activity and increased calcium and collagen production compared to less interconnected scaffolds. These findings emphasise the importance of scaffold interconnectivity in BTE for efficient nutrient transport, facilitating cell migration and infiltration, and supporting the development of interconnected cell networks that positively influence osteogenic differentiation.

Cell-based therapies are gaining attention as a promising approach for repairing damaged tissues and organs, offering alternatives to invasive treatments like organ transplants and powerful medications. Recent research has shifted towards extracellular vesicles (EVs), membrane-bound particles that can carry therapeutic compounds like DNA, RNA, and proteins, which may offer advantages over cell-based therapies, such as higher potency and reduced immune reactions. A key challenge in EV therapy is ensuring that the vesicles reach their intended target tissues. While EVs are often delivered via injection, systemic administration can result in off-target effects. To address this, we highlight the microfluidic encapsulation of EVs in hydrogel microcapsules that include a CD9 binding peptide (CD9BP), allowing for controlled EV release in response to a shift in environmental pH. By encapsulating CD9+ EVs in CD9BP hydrogel capsules, we demonstrate the release of their contents in acidified environments typical of damaged tissues. This method allows for targeted, localized EV delivery. The approach promises more effective tissue regeneration while reducing the need for broad, non-specific drug delivery.

The global rise in chronic kidney disease necessitates innovative solutions for end-stage renal disease that can help to overcome the limitations of the only available treatment options, transplantation and dialysis. Tissue engineering presents a promising alternative, leveraging decellularized scaffolds to retain the extracellular matrix (ECM). However, optimizing methods for decellularization and recellularization remains a challenge. Here we present novel work which builds on our previous study where we investigated several decellularization protocols. In this study we analyzed the suitability of decellularized scaffolds for recellularization. Precision-cut kidney slices (PCKS) were utilized as a model to explore the impact of different decellularization protocols on scaffold recellularization. PCKS were pretreated physically followed by immersion decellularization in chemicals (CHEM-Imm). Physical pretreatments included high hydrostatic pressure (HHP-Imm) or freezing-thawing cycles (FTC-Imm). Scaffolds were recellularized, with human renal proximal tubular epithelial cells (RPTEC/TERT1). All scaffolds showed cell growth over the 7 d incubation period. Notably, FTC-Imm demonstrated the highest expression of the tight junction protein zonula-occludens-1 (ZO-1). Moreover, as the native kidney is composed of up to 30 different cell types, we utilized artificial neural networks to investigate the distribution and attachment patterns of RPTEC/TERT1 cells to determine if decellularized scaffolds retain cell specific attachment sites. It was revealed that, at least 97% of RPTEC/TERT1 cells were attached outside the Bowman capsules, potentially showing a clear tendency to attach to their original tubular sites. This suggests that the ECM retains instructive cues guiding the migration and attachment of the cells. Overall, our scoring system identified FTC-Imm as the most effective method.

β-Tricalcium phosphate (β-TCP) is widely used as a material for bone implants due to its excellent biocompatibility, biodegradability, and osteoconductivity, as well as its osteoinductive properties. Here, we demonstrate that the regenerative potential of this material can be significantly enhanced when incorporated into a matrix of inorganic polyphosphate (polyP), a physiological, metabolically active polymer composed of phosphate residues linked by high-energy phosphoanhydride bonds. A 3D-printable hydrogel was developed containing suspendedβ-TCP and amorphous calcium-polyP nanoparticles (Ca-polyP-NP; the water-insoluble depot form of polyP), as well as NaH₂PO₄as the monomeric precursor of the polymeric, water-soluble Na-polyP. Heating the printed scaffold to 700 °C causes condensation of NaH₂PO₄, resulting in the formation of a Na-polyP glass melt that embeds the Ca-polyP-NP andβ-TCP particles. The final scaffolds exhibited the necessary porosity, with pore sizes ranging from 10 to 100 µm (average 84 µm), which are suitable for bone ingrowth, along with the required mechanical stability. The morphogenetically active polyP component is released from the 3D-printed porous scaffolds in appropriate amounts, significantly increasing both the proliferation and energy-dependent differentiation of mesenchymal stem cells (MSCs) into mineralizing osteoblasts compared to polyP-freeβ-TCP scaffolds. Moreover, enhanced formation of collagen fibers and hydroxyapatite deposits on the cell surface, as well as accelerated microvessel tube formation, were observed in MSCs seeded on polyP-containing scaffolds. These results d`emonstrate that the novel strategy of integratingβ-TCP with polyP as an energy-supplying, regeneration-promoting component imparts superior functional properties toβ-TCP scaffolds, making them a promising material for future bone implant applications.

Leukaemia is a haematopoietic system malignancy depicted by the infiltration of the bone marrow, blood and other tissues by proliferative and abnormally differentiated cells of the haematopoietic system. The available therapies aim to induce cell death of these poorly differentiated cells by various means. The anthracycline doxorubicin (DOX) regime remains the standard first-line treatment for leukaemia. DOX has potent anticancer activity at higher dosage concentration and imparts cardiac, renal and hepatic toxicity. The disulfiram metabolite complex zinc diethyldithiocarbamate (Zn-DDC) has potent anticancer efficacy; however, it has a short half-life due to its instability in gastric juice and the blood stream. The present study employed a thin-film hydration method to synthesise liposomal nanoparticles encapsulating DOX (DOX-NPs), Zn-DDC (Zn-DDC-NPs) and both Zn-DDC and DOX (Zn-DDC + DOX-NPs).In vitrocytotoxicity and antioxidant assays were performed to assess their cytotoxicity and antioxidant activity. The liposomes were evaluated against leukaemia in Wistar rats. After leukaemia induction through benzene, haematological and serological assays, morphological and histological examinations were conducted to evaluate treatment approaches. All liposomal formulations overcame their limitations, improved the blood parameters (p> 0.05), restored the hepatic and renal enzyme levels (p> 0.05), and reduced the blast cells in blood and tissues. However, in co-encapsulated liposomes, Zn-DDC reduced the cytotoxicity caused by DOX and provided results more analogous to normal.