Materials science & engineering. C, Materials for biological applications最新文献

Calcium phosphate coating is an attractive surface modification strategy for magnesium alloys, since it can increase their corrosion resistance and endow them with osteogenic function simultaneously. Herein, a calcium metaphosphate (CMP) coating was fabricated on magnesium alloy by using sol-gel approach assisted with micro-arc oxidation pre-treatment. Scanning electron microscopy showed that the micro-pores and cracks in micro-arc oxidation inner layer generated during the pre-treatment process were sealed by the grainy sol-gel outer layer. Energy dispersive spectrometry and X-ray diffraction results demonstrated the identity of the coating as CMP. The cross-cut test showed that the adhesion of CMP coating was strong. Applying bare magnesium alloy substrate as a control, the CMP coating surface was rougher and more hydrophilic. The potentiodynamic polarization test demonstrated that the corrosion resistance was significantly improved by using CMP coating. Hydrogen evolution in immersion test further confirmed that the degradation rate was decelerated within 14 days. Moreover, CMP coating facilitated the adhesion speed, spreading area, and focal adhesion formation of bone marrow stem cells. The number of cells in the active proliferating state and proliferated cells present on the CMP coating also increased. Additionally, CMP coating upregulated alkaline phosphatase activity and osteogenic gene expression in cells. In summary, the micro-arc oxidation assisted sol-gel CMP coatings increased the corrosion resistance and promoted the interfacial cell behavior for magnesium alloy implants, which might inform the further development of surface modifications on magnesium alloys for bone related applications.

Currently, the combining photodynamic therapy (PDT) with photothermal therapy (PTT) modalities based on a single near infrared (NIR) laser irradiation and highly selective internalization still remain a challenge. Herein, a hierarchical dual-responsive cleavable nanosystem for synergetic NIR triggered PDT/PTT is reported. The engineered nanoplatform (Au NRs/Cur/UCNPs@PBE) is designed by loading curcumin (Cur, photosensitizer) on gold nanarods (Au NRs) to build PDT/PTT therapy system, which was encapsulated outside with upconversion nanoparticles (UCNPs) and then modified with phenylboronic double ester (PBE). The pH and ROS-responsive feature made Au NRs/Cur/UCNPs@PBE provide a fundamental structural evolution and improve the specificity and intracellular accumulation to tumors. Au NRs/Cur/UCNPs@PBE exhibited significant PDT and PTT efficiency against two type melanoma cells due to upconversion nanoparticles and Au NRs induced by an 808 nm laser. Notably, the platform can mainly activate apoptosis and partial ferroptosis to achieve the synergistic PDT/PTT, furthermore, the integrated PDT with PTT using Au NRs/Cur/UCNPs@PBE showcased a great antitumor efficacy in vivo superior to the other alone treatment. Our findings highlight that this intelligent nanoagents for synergistic phototherapy facilitate enhanced fighting melanoma and provide a promising strategy for melanoma theranostics.

Porous Ti6Al4V scaffolds are characterized by high porosity, low elastic modulus, and good osteogenesis and vascularization, which are expected to facilitate the repair of large-scale bone defects in future clinical applications. Ti6Al4V scaffolds are divided into regular and irregular structures according to the pore structure, but the pore structure more capable of promoting bone regeneration and angiogenesis has not yet been reported. The purpose of this study was to explore the optimal pore structure and pore size of the Ti6Al4V porous scaffold for the repair of large-area bone defects and the promotion of vascularization in the early stage of osteogenesis. 7 groups of porous Ti6Al4V scaffolds, named NP, R8, R9, R10, P8, P9 and P10, were fabricated by Electron-beam-melting (EBM). Live/dead staining, immunofluorescence staining, SEM, CCK8, ALP, and PCR were used to detect the adhesion, proliferation, and differentiation of BMSCs on different groups of scaffolds. Hematoxylin-eosin (HE) staining and Van Gieson (VG) staining were used to detect bone regeneration and angiogenesis in vivo. The research results showed that as the pore size of the scaffold increased, the surface area and volume of the scaffold gradually decreased, and cell proliferation ability and cell viability gradually increased. The ability of cells to vascularize on scaffolds with irregular pore sizes was stronger than that on scaffolds with regular pore sizes. Micro-CT 3D reconstruction images showed that bone regeneration was obvious and new blood vessels were thick on the P10 scaffold. HE and VG staining showed that the proportion of bone area on the scaffolds with irregular pores was higher than that on scaffolds with regular pores. P10 had better mechanical properties and were more conducive to bone tissue ingrowth and blood vessel formation, thereby facilitating the repair of large-area bone defects.

3D printing enables a better control over the microstructure of bone restoring constructs, addresses the challenges seen in the preparation of patient-specific bone scaffolds, and overcomes the bottlenecks that can appear in delivering drugs/growth factors promoting bone regeneration. Here, 3D printing is employed for the fabrication of an osteogenic construct made of hydrogel nanocomposites. Alginate dialdehyde-gelatin (ADA-GEL) hydrogel is reinforced by the incorporation of bioactive glass nanoparticles, i.e. mesoporous silica-calcia nanoparticles (MSNs), in two types of drug (icariin) loading. The composites hydrogel is printed as superhydrated composite constructs in a grid structure. The MSNs not only improve the mechanical stiffness of the constructs but also induce formation of an apatite layer when the construct is immersed in simulated body fluid (SBF), thereby promoting cell adhesion and proliferation. The nanocomposite constructs can hold and deliver icariin efficiently, regardless of its incorporation mode, either as loaded into the MSNs or freely distributed within the hydrogel. Biocompatibility tests showed that the hydrogel nanocomposites assure enhanced osteoblast proliferation, adhesion, and differentiation. Such optimum biological properties stem from the superior biocompatibility of ADA-GEL, the bioactivity of the MSNs, and the supportive effect of icariin in relation to cell proliferation and differentiation. Taken together, given the achieved structural and biological properties and effective drug delivery capability, the hydrogel nanocomposites show promising potential for bone tissue engineering.

Corneal opacities are the 4th leading cause of blindness, and the only current treatment method is the replacement of damaged tissue with a donor cornea. The worldwide shortage of donor eye bank tissue has influenced research into biomaterial substrates for both partial and full thickness corneal implantation. Here, polymer hydrogels based on natural peptides, poly-ɛ-lysine and gellan gum, can be manufactured using reactive inkjet printing (RIJ). The inks used for printing were optimised based on their rheological properties. Printing alternating layers of ink forms a unique surface pattern, based on the immediate formation of ionic bonds between polymers of opposing charges. This surface pattern resembles a repeating honeycomb-like structure, visible by both optical and scanning electron microscopy. The structure of the printed hydrogels can be modified to include pores, a feature of interest for the tissue engineering of full thickness corneal constructs. Printed poly-ɛ-lysine/gellan gum hydrogels demonstrated a transparency of 80% and cyto-compatibility with both corneal epithelial and endothelial cells. Both corneal cell types demonstrated cell attachment across the surface of the printed hydrogel arrays, displaying their typical cell morphology. This gives confidence of the cyto-compatibility of these hydrogels in vitro. Reactive inkjet printing can produce 3D structures with a high resolution, producing printed tracks in the micron range. Additionally, RIJ demonstrates versatility, as constructs can be tailored to meet various dimension and thickness requirements. Furthermore, this work demonstrates for the first time that reactive inkjet printing can been used to produce hydrogel constructs based on these two inks, with the aim of producing constructs for corneal tissue engineering.

Conventional applications of transplant technology, applied to severe traumatic injuries of the nervous system, have met limited success in the clinics due to the complexity of restoring function to the damaged tissue. Neural tissue engineering aims to deploy scaffolds mimicking the physiological properties of the extracellular matrix to facilitate the elongation of axons and the repair of damaged nerves. However, the fabrication of ideal scaffolds with precisely controlled thickness, texture, porosity, alignment, and with the required mechanical strength, features needed for effective clinical applications, remains technically challenging. We took advantage of state-of-the-art 2-photon photolithography to fabricate highly ordered and biocompatible 3D nanogrid structures to enhance neuronal directional growth. First, we characterized the physical and chemical properties and proved the biocompatibility of said scaffolds by successfully culturing primary sensory and motor neurons on their surface. Interestingly, axons extended along the fibers with a high degree of alignment to the pattern of the nanogrid, as opposed to the lack of directionality observed on flat glass or polymeric surfaces, and could grow in 3D between different layers of the scaffold. The axonal growth pattern observed is highly desirable for the treatment of traumatic nerve damage occurring during peripheral and spinal cord injuries. Thus, our findings provide a proof of concept and explore the possibility of deploying aligned fibrous 3D scaffold/implants for the directed growth of axons, and could be used in the design of scaffolds targeted towards the restoration and repair of lost neuronal connections.

The reason for low- or non-immunogenicity of fish collagens is still in doubt, which, to some extent, bottlenecks their production and clinical application as biomaterials. Employing bovine or porcine type I collagens (BCI or PCI) as controls in this paper, we intensively investigate the influence of tilapia type I collagens (TCI) on the function of dendritic cells (DCs) and T cells. From bio-informatic analyses, as well as data obtained in vitro and in vivo, we find the variations in amino acid sequences lead to only one calcium binding motif in the secondary structure of TCI, compared with three in BCI or PCI. So when TCI (together with the minor amount of Ca²⁺ they take) are uptaken, intracellular [Ca²⁺] remains stable and DCs maintain immature. On the contrary, those that have uptaken PCI or BCI experience not only increased [Ca²⁺] in the plasma but also phosphorylation of p65, resulting in activation of STIM1-Orai1/NF-кB signaling pathway and DC maturation. We fully prove our results on mice models, with no obvious cellular and humoral immune reactions. Our study primarily reveal the underlying mechanisms why TCI, different from BCI or PCI, show almost non-immunogenicity. Our findings are of great importance for the promotion and wide application of TCI in biomedicine.