Biomedical materials (Bristol, England)最新文献

Titanium has been widely employed in the fields of orthopaedics and dentistry, attributed to its superior mechanical and biological properties. The mechanical stimulation induced by the titanium dioxide (TiO2) nanotubes (TNTs) morphology resulting from surface modification has been demonstrated to enhance the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Kindlin-2, a pivotal focal adhesion protein, is involved in mechanical signaling processes through the regulation of stress fibril filament assembly. Additional research is needed to clarify the involvement of Kindlin-2 in the mechanism of TNTs-induced osteogenic differentiation. This study systematically investigated the impact of Kindlin-2 on TNTs-induced osteogenesis and mechanotransduction. TiO2 nanotubes with diameters of approximately 30 nm (TNT-30) and 100 nm (TNT-100) were fabricated and characterized using anodic oxidation. The results showed that TNT-100 significantly increased the expression of Kindlin-2 and enhanced osteogenic differentiation compared to polished titanium (PT) and TNT-30. Additionally, Kindlin-2 promotes cytoskeleton assembly by regulating the integrin β1/FAK/RhoA signaling pathway, impacting osteogenic gene expression and BMSC differentiation in a Yes-Associated Protein (YAP)-dependent manner. Therefore, these findings contribute to a more comprehensive understanding of the fate of BMSCs on TNTs morphologies and provide a novel theoretical foundation for the development of advanced bone repair biomaterials.

Medical dressings with multifunctional properties, including potent regeneration capability and good biocompatibility, are increasingly needed in clinical practice. In this study, we reported a novel hybrid wound dressing (PCL/SerMA/DMOG) that combines electrospun PCL membranes with DMOG-loaded methacrylated sericin (SerMA) hydrogel. In such a design, DMOG molecules are released from the hybrid dressing in a sustained mannerin vitro. A series ofin vitroassays demonstrated that DMOG-loaded hybrid dressing has multiple biological functions, including promotion of human umbilical vein endothelial cells proliferation and migration,in vitrovascularization, and the generation of intracellular NO. When applied to the cutaneous wound, the PCL/SerMA/DMOG dressing significantly accelerated wound closure and tissue regeneration by promoting angiogenesis in the wound area, collagen deposition, and cell proliferation within the wound bed. These results highlight the potential clinical application of PCL/SerMA/DMOG hybrid dressings as promising alternatives for accelerating wound healing via improved biocompatibility and angiogenesis amelioration.

Osteosarcoma (OS) is the mostly commonly occurring primary bone cancer. Despite comprehensive treatment programs including neoadjuvant chemotherapy and tumour resection, survival rates have not improved significantly since the 1970s. Survival rates are dramatically reduced for patients who suffer a local recurrence. Furthermore, primary bone cancer patients are at increased risk of bone fractures. Consequently, there is an urgent need for alternative treatment options. In this paper we report the development of novel gallium doped bioactive glass that selectively kill bone cancer cells whilst simultaneously stimulating new bone growth. Here we show, using a combination of 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide, LIVE/DEAD assays and image analysis, that bioactive glasses containing gallium oxide are highly toxic and reduce both the proliferation and migration of bone cancer cells (Saos-2) in a dose dependant manner. Glasses containing 5 mol% gallium oxide reduced the viability of OS cells by 99% without being cytotoxic to the non-cancerous normal human osteoblasts (NHOst) control cells. Furthermore, Fourier transform infrared and energy-dispersive x-ray spectroscopy results confirmed the formation of an amorphous calcium phosphate/hydroxyapatite like layer on the surface of the bioactive glass particulates, after 7 d incubating in simulated body fluid, indicating the early stages of bone formation. These materials show significant potential for use in bone cancer applications as part of a multimodal treatment.

Bone tissue engineering (BTE) aims to promote bone regeneration by means of the synergistic effect of biomaterials, cells, and other factors, as potential alternative to conventional treatments for bone fractures. To this aim, a composite material was developed, based on collagen type I, strontium-enriched mesoporous bioactive glasses, and hydroxyapatite nanorods as bioactive and biomimetic components. Nanostructured scaffolds were 3D printed and subsequently chemically crosslinked with genipin to improve mechanical properties and stability. The developed nanostructured system was maintained in culture until 3 weeks with a co-culture of human bone cells to provide anex vivomodel of bone microenvironment and examine the cellular crosstalk and signaling pathways through paracrine cell activities. Human osteoblasts (OBs), derived from trabecular bone, and human osteoclast precursors (OCs), isolated from buffy coat samples were involved, with OBs seeded on the scaffold and OC precursors seeded in a transwell device. When compared to the material without inorganic components, the bioactive and biomimetic scaffold positively influenced cell proliferation and cell metabolic activity, boosting alkaline phosphatase activity of OBs, and reducing OC differentiation. Thus, the bioactive and biomimetic system promoted an enhanced cellular response, highlighting its potential application in BTE.

Regenerative medicine is continuously looking for new natural, biocompatible and possibly biodegradable materials, but also mechanically compliant. Chitosan is emerging as a promising FDA-approved biopolymer for tissue engineering, however, its exploitation in regenerative devices is limited by its brittleness and can be further improved, for example by blending it with other materials or by tuning its superficial microstructure. Here, we developed membranes made of chitosan (Chi) and glycerol, by solvent casting, and micro-patterned them with directional geometries having different levels of axial symmetry. These membranes were characterized by light microscopies, atomic force microscopy (AFM), by thermal, mechanical and degradation assays, and also testedin vitroas scaffolds with Schwann cells (SCs). The glycerol-blended Chi membranes are optimized in terms of mechanical properties, and present a physiological-grade Young's modulus (≈0.7 MPa). The directional topographies are effective in directing cell polarization and migration and in particular are highly performant substrates for collective cell migration. Here, we demonstrate that a combination of a soft compliant biomaterial and a topographical micropatterning can improve the integration of these scaffolds with SCs, a fundamental step in the peripheral nerve regeneration process.

Artificial bone is the alternative candidate for the bone defect treatment under the circumstance that there exits enormous challenge to remedy the bone defect caused by attributes like trauma and tumors. However, the impact of pore size discrepancy for regulating new bone generation is still ambiguous. Using direct 3D printing technology, customized 3D polycaprolactone/β-tricalcium phosphate (PCL/β-TCP) artificial bones with different structural pore sizes (1.8, 2.0, 2.3, 2.5, and 2.8 mm) were successfully prepared, abbreviated as the 3D PCL/β-TCP. 3D PCL/β-TCP exhibited a 3D porous structure morphology similar to natural bone and possessed outstanding mechanical properties. Computational fluid dynamics analysis indicated that as the structural pore size increased from 1.8 to 2.8 mm, both velocity difference (from 4.64 × 10^-5to 7.23 × 10^-6m s^-1) and depressurization (from 7.17 × 10^-2to 2.25 × 10^-2Pa) decreased as the medium passed through.In vitrobiomimetic mineralization experiments confirmed that 3D PCL/β-TCP artificial bones could induce calcium-phosphate complex generation within 4 weeks. Moreover, CCK-8 and Calcein AM live cell staining experiments demonstrated that 3D PCL/β-TCP artificial bones with different structural pore sizes exhibited advantageous cell compatibility, promoting MC3T3-E1 cell proliferation and adhesion.In vivoexperiments in rats further indicated that 3D PCL/β-TCP artificial bones with different structural pore sizes promoted new bone formation, with the 2.5 mm group showing the most significant effect. In conclusion, 3D PCL/β-TCP artificial bone with different structural pore sizes could promote new bone formation and 2.5 mm group was the recommended for the bone defect repair.

Traditional cell culture methods often fail to accurately replicate the intricate microenvironments crucial for studying specific cell growth patterns. In our study, we developed a 4D cell culture model-a precision instrument comprising an electromagnet, a force transducer, and a cantilever bracket. The experimental setup involves placing a Petri dish above the electromagnet, where gel beads encapsulating magnetic nanoparticles and tongue cancer cells are positioned. In this model, a magnetic force is generated on the magnetic nanoparticles in the culture medium to drive the gel to move and deform when the magnet is energized, thereby exerting an external force on the cells. This setup can mimic the microenvironment of tongue squamous cell carcinoma CAL-27 cells under mechanical stress induced by tongue movements. Electron microscopy and rheological analysis were performed on the hydrogels to confirm the porosity of alginate and its favorable viscoelastic properties. Additionally, Calcein-AM/PI staining was conducted to verify the biosafety of the hydrogel culture system. It mimics the microenvironment where tongue squamous cell carcinoma CAL-27 cells are stimulated by mechanical stress during tongue movement. Electron microscopy and rheological analysis experiments were conducted on hydrogels to assess the porosity of alginate and its viscoelastic properties. Calcein-AM/PI staining was performed to evaluate the biosafety of the hydrogel culture system. We confirmed that the proliferation of CAL-27 tongue squamous cells significantly increased with increased matrix stiffness after 5 d as assessed by MTT. After 15 d of incubation, the tumor spheroid diameter of the 1%-4D group was larger than that of the hydrogel-only culture. The Transwell assay demonstrated that mechanical stress stimulation and increased matrix stiffness could enhance cell aggressiveness. Flow cytometry experiments revealed a decrease in the number of cells in the resting or growth phase (G0/G1 phase), coupled with an increase in the proportion of cells in the preparation-for-division phase (G2/M phase). RT-PCR confirmed decreased expression levels of P53 and integrinβ3 RNA in the 1%-4D group after 21 d of 4D culture, alongside significant increases in the expression levels of Kindlin-2 and integrinαv. Immunofluorescence assays confirmed that 4D culture enhances tissue oxygenation and diminishes nuclear aggregation of HIF-1α. This device mimics the microenvironment of tongue cancer cells under mechanical force and increased matrix hardness during tongue movement, faithfully reproducing cell growthin vivo, and offering a solid foundation for further research on the pathogenic matrix of tongue cancer and drug treatments.

Hydrogels have excellent swelling properties and have been widely applied in tissue engineering because of their similarity to the extracellular matrix (ECM). Sodium alginate (SA) and carboxymethyl chitosan (CMCS) were prepared into hydrogel microspheres with Ca²⁺crosslinking in our study. The morphology, inner structure, mechanical properties, water content, swelling rate and BMP-2 loading and releasing properties were characterized. Our results showed that the composite SA /CMCS hydrogel microspheres were translucent and spherical in shape with uniform particle size. The incorporation of CMCS further increased the diameters of the microspheres, internal pore structure, water content, and mechanical properties of the SA/CMCS hydrogel microspheres. At the same SA concentration, with the increase of CMSC concentration, the diameter of microspheres could be increased by about 0.4 mm, the water content can be increased about 1%-2%. As for the mechanical properties, the compressive strength can be increased by 0.04-0.1 MPa, and the modulus of elasticity can be increased by 0.1-0.15 MPa. BMP-2 was chosen as a model agent and it could be loaded into SA/CMCS microspheres, and the incorporation of CMCS increased BMP-2 loading. The encapsulated BMP-2 was sustainably releasedin vitro. The leaching solutions of the SA/CMCS hydrogel microspheres exhibited good cytocompatibility and could increase ALP activity, ALP expression, and biomineralization on MC3T3-E1 cells. After 7 d of co-culture, ALP activities in S2.5C2 and S2.5C3 groups was increased by 50% and 45% compared with that of the control group. When embedded in the SA/CMCS microspheres, the MC3T3-E1 cells were evenly distributed inside the hydrogel microspheres and remained viable. Transcriptomic studies showed that incorporation of CMCS induced upregulation of 1141 differentially expressed genes (DEGs) and downregulation of 1614 DEGs compared with SA microspheres. The most significantly enriched pathways were the Wnt and MAPK signaling pathways induced by the incorporation of CMCS and BMP-2. In conclusion, our results indicated that the physiochemical characteristics of the SA hydrogel microspheres could be greatly modulated by CMCS to better mimic the ECM microenvironment and induce osteo-inductive activities of MC3T3-E1 cells.

The invasion and metastasis of tumors pose significant challenges in the treatment of ovarian cancer (OC), making it difficult to cure. One potential treatment approach that has gained attention is the use of matrix metalloproteinase reactive controlled release micelle preparations. In this study, we developed a novel PEG₅₀₀₀-PVGLIG-hyaluronic acid docetaxel/bakuchiol (PP-HA-DTX/BAK) micelles formulation with desirable characteristics such as particle size, narrow polydispersity index, and a ZETA potential of approximately -5 mV. The surface modification with HA facilitates tumor penetration into the tumor interior, while the incorporation of DSPE-PEG₂₀₀₀-PVGLIG-PEG₅₀₀₀helps conceal DSPE-PEG₂₀₀₀-HA, reducing off-target effects and prolonging drug circulation timein vivo. Bothin vitroandin vivoexperiments demonstrated that these micelles effectively inhibit proliferation, invasion, and metastasis of OC cells while promoting apoptosis. Therefore, our findings suggest that PP-HA-DTX/BAK micelles represent a safe and effective therapeutic strategy for treating OC.

Electrospinning is a versatile and straightforward technique to produce nanofibrous mats with different morphologies. In addition, by optimizing the solution, processing, and environmental parameters, three-dimensional (3D) nanofibrous scaffolds can also be created using this method. In this work, the preparation and characterization of bioactive glass (BG) scaffolds based on the SiO₂-CaO sol-gel system, a biomaterial with a highly reactive surface, is reported. The electrospinning technique was combined with sol-gel methods to obtain nanofibrous 3D cotton wool-like scaffolds. The addition of zinc and copper ions to the silica-calcia system was examined, and the influence of these ions on the material properties and characteristics was investigated by various characterization techniques, from morphological and chemical properties to antibacterial and wound closure capability, cell viability and ion release. Our findings show that the cotton wool-like ion-doped nanofibers are promising for wound healing applications.