Cell Cytocompatibility Research Articles

Silk nano-discs: A natural material for cancer therapy.

The article demonstrates the crystalline silk nano-discs (CSNs), with well-controlled morphology, which upon magnetization, yields magnetic crystalline silk nano-discs, making both prominent alternatives for replacing metal templates such as gold, silver, and so on in therapeutics and implants. The isolated β-sheet-rich discotic CSNs have ~50 nm diameter, high crystallinity (> 90%), and are insoluble but provide good dispersibility and stability in aqueous solutions. The melt blending-cum-electrospinning of functionalized CSN with poly(lactic acid) results in biocompatible nanofiber-based scaffolds having in vitro cell cytocompatibility with improved cell adhesion and proliferation. The assessment of release behavior of curcumin, a naturally occurring anticancer drug, shows sustained release over 25 days exhibiting effective cytotoxicity against human cervical cancer cells. Further, combined effect of curcumin and hyperthermia reduced the cell growth by ~63%. Alignment of CSN-derived magnetic nanoparticles due to effective fiber drawing process during electrospinning could improve cytocompatibility against BHK-21 cells, and therefore efficacy for cancer therapy.

Preparation of Icariin and Deferoxamine Functionalized Poly(l-lactide)/chitosan Micro/Nanofibrous Membranes with Synergistic Enhanced Osteogenesis and Angiogenesis.

Osteogenesis is tightly complemented with angiogenesis during the bone regeneration process. In this study, to synergistically enhance the osteogenesis and angiogenesis of poly(l-lactide) (PLLA), PLLA/chitosan (PLLA/CS) composite fibrous membrane was prepared first by combining electrospinning and thermally induced phase separation technologies. Then, with the aid of polydopamine (PDA) coating, two types of bioactive molecules of icariin (ICA) and deferoxamine (DFO) were chosen to singly or simultaneously surface modify the as-prepared PLLA/CS-PDA membrane, thereby fabricating PLLA/CS-PDA/ICA, PLLA/CS-PDA/DFO, and PLLA/CS-PDA/ICA/DFO membranes. The morphology and properties of the pristine and modified PLLA fibrous membranes were studied, which revealed that the modified PLLA membrane's own hierarchical fibrous structure improved hydrophilicity and had better tensile properties by introducing PDA and ICA or DFO. On account of the synergetic contributions of ICA and DFO as well as the hierarchical fibrous structure, the PLLA/CS-PDA/ICA/DFO membrane exhibited superior cytocompatibility and osteogenic activity of MC3T3-E1 cells compared to other membranes, which was confirmed by the enhanced cell adhesion, proliferation, osteogenic differentiation, and mineralization. Besides, compared with those without or single immobilization of ICA or DFO, the PLLA/CS-PDA/ICA/DFO membrane with ICA and DFO together could significantly promote the growth and expression of angiogenic-related factors of HUVECs. Particularly, ICA not only exhibits favorable osteogenic activity but also shows superior angiogenic activity even compared to DFO. On the contrary, DFO possesses well-known angiogenic activity but manifests a better osteogenic activity compared with ICA. Overall, our study demonstrated that the PLLA/CS-PDA/ICA/DFO membrane exerts synergistic effects on osteogenesis and angiogenesis, thereby holding great potentials as a substitute for bone repair.

Soy protein isolate/bioactive glass composite membranes: Processing and properties

Composite biomaterials based on proteins and inorganic fillers are highly attractive for wound dressing applications due to their highly absorbent properties towards blood and exudate provided by the inorganic fillers. Moreover, such composites offer a desirable environment for cells due to the combination of organic and inorganic characteristics. This study highlights the fabrication of soy protein isolate/nanoscale bioactive glass composite films by solvent casting method as a matrix for wound-dressing applications. The effect of the addition of bioactive glass nano particles on blood clotting was assessed. Cytotoxicity and in vitro cytocompatibility of the films were also tested. The results showed that the composite films could meet the essential requirements for an appropriate wound dressing with additional favorable properties such as hemostatic capability and mechanical properties as well as significant cell cytocompatibility.

Magnetic Nanoparticles Associated PEG/PLGA Block Copolymer Targeted with Anti-Transferrin Receptor Antibodies for Alzheimer's Disease.

A facile brain drug delivery system for Alzheimer's disease, the Magnetic iron oxide (Fe3O4) nanoparticles loaded with polyethylene glycol-polylactide-polyglycolide co-polymer nanocomposite was fabricated with anti-transferrin monoclonal antibody (OX26) receptor in this present research work with its in vitro delivery properties evaluated by using clioquinol. TEM microscopic analysis confirmed the presence of active MNPs on the surface of OX26-PEG/PLGA nanocomposite matrix. The results of in vitro cell cytocompatibility studies of MNPs incorporated OX26-PEG/PLGA matrix showed a more favorable environment and increasing cell viability in normal human neuroblastoma SH-SY5Y cells than that of raw MNPs and PEG/PLGA co-polymer matrix. All these structural and in vitro studies results revealed that MNPs-PEG/PLGA-OX26 nanocomposite was a promising brain drug delivery system and it's potential for the Alzheimer's diseases.

Killing two birds with one stone: To eliminate the toxicity and enhance the photocatalytic property of CdS nanobelts by assembling ultrafine TiO2 nanowires on them

Although CdS has been proven to be one of the best photocatalysts in visible light region, its photocorrosion characteristics and toxicity prohibit its practical applications in photocatalytic hydrogen generation and photodegradation of organic pollutants in waste water. In addition, the photocatalytic efficiency of single phase CdS nanostructure is still low due to the recombination of photo-induced carriers. In this paper, a facile modification of CdS nanobelts approach is proposed by assembling TiO2 nanowire on the surface of CdS nanobelts to form TiO2 nanowire/CdS nanobelt hybrid nanstructures. This approach can kill two birds with one stone, that is, to eliminate the photocorrosion induced nontoxicity, and enhance photocatalytic properties by inducing UV light active TiO2 nanowires, and enhance the photo-induced carrier separation ability. The cell cyto-compatibility experiments on TiO2 nanowire/CdS nanobelt hybrid photocatalyst proved that the toxicity of CdS nanobelts can be totally eliminated. At the same time, photodegradation performance of for CdS/TiO2 is over 3 times of that for CdS nanobelts and10 times of that for TiO2. This work gives a new insight in the field of photocatalytic water treatment.

Study on structure, mechanical property and cell cytocompatibility of electrospun collagen nanofibers crosslinked by common agents

Collagen electrospun scaffolds properly reproduce the framework of the extracellular matrix (ECM) of tissues that are natural with the fibrous morphology of the protein by coupling large biomimetism of the biological material. However, traditional solvents employed for collagen electrospinning lead to poor mechanical attributes and bad hydro-stability. In this work, by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride with N-hydroxysulfosuccinimide (EDC-NHS), glutaraldehyde (GTA) and genipin (GP) respectively, electrospun collagen fibers cross-linked, effectively stabilized the fiber morphology over 2months and improved the mechanical properties in both dry and wet state, especially EDC-NHS with large ultimate tensile stress and εb. The secondary structure of collagen structure still remained and had no obvious difference among various crosslinked samples according to FTIR. On the cell assessment, electrospun collagen fibers crosslinked by EDC-NHS, GTA and GP, were found to support cell adhesion, spreading and proliferation of MC3T3-E1. By contrast, GTA was more effective in preserving explicit fibrous morphology with a relatively lower cell viability both in FBS and BSA soaked mats. Interestingly, GP also had the similar cytocompatibility of MC3T3-E1 as EDC-NHS did. The study proved the feasibility of chemical crosslinker to electrospun collagen for biomedical application.

Cytocompatibility of Titanium Microsphere-Based Surfaces.

The topography at the micro/nanoscale level for biomaterial surfaces has been thought to play vital roles in their interactions with cells. However, discovering the interdisciplinary mechanisms underlying how cells respond to micro-nanostructured topography features still remains a challenge. In this work, ∼37 μm 3D printing used titanium microspheres and their further hierarchical micro-nanostructured spheres through hydrothermal treatment were adopted to construct typical model surface topographies to study the preosteoblastic cell responses (adhesion, proliferation, and differentiation). We here demonstrated that not only the hierarchical micro-nanostructured surface topography but also their distribution density played critical role on cell cytocompatibility. The microstructured topography feature surface with middle-density distributed titanium microspheres showed significantly enhanced cell responses, which might be attributed to the better cellular interaction due to the cell aggregates. However, the hierarchical micro-nanostructured topography surface, regardless of the distribution density of titanium microspheres, improved the cell-surface interactions because of the enhanced initial protein adsorption, thereby reducing the cell aggregates and consequently their responses. This work, therefore, provides new insights into the fundamental understanding of cell-material interactions and will have a profound impact on further designing micro-nanostructured topography surfaces to control cell responses.

Effects of copper nanoparticles in porous TiO2 coatings on bacterial resistance and cytocompatibility of osteoblasts and endothelial cells

Copper (Cu) has garnered increasing interest due to its excellent antimicrobial activity and important roles in human metabolism. Although the biological effects of Cu have been studied, the effects of Cu nanoparticles (NPs) on cell behavior are not well understood. In this study, porous TiO2 coatings doped with different amounts of Cu NPs (designated as 0 Cu, 0.3 Cu, and 3.0 Cu) are deposited on titanium by micro-arc oxidation (MAO). The Cu NPs coated samples exhibit excellent antibacterial activity against Staphylococcus aureus (S. aureus). In vitro cytocompatibility evaluation discloses that 0 Cu and 0.3 Cu have no toxicity to osteoblasts but 3.0 Cu shows cytotoxicity. 0.3 Cu promotes proliferation and adhesion of osteoblasts and enhances extracellular matrix mineralization (ECM), but has little effects on the alkaline phosphatase activity (ALP) and collagen secretion. Surprisingly, the Cu NPs coated samples show a different behavior with endothelial cells. Both 0.3 Cu and 3.0 Cu show no cytotoxicity on endothelial cells and promote cell proliferation. Production of nitric oxide (NO) and secretion of vascular endothelial growth factor (VEGF) by the endothelial cells are observed from the Cu NPs doped TiO2 coatings.

Improved cytocompatibility of Mg-1Ca alloy modified by Zn ion implantation and deposition

The Mg-1Ca alloy has been modified by Zn ion implantation and deposition (II&D) using metal vapor vacuum arc plasma source (MEVVA). The surface characteristics, corrosion behavior and cytocompatibility were investigated. The auger electron spectroscopy (AES) results showed that a uniform ZnO layer was formed on the surface of Mg-1Ca alloy. The electrochemical measurements revealed that the corrosion potential has been increased, and a comparable corrosion current density in the simulated body fluid (SBF) was obtained for the Zn-modified Mg-1Ca alloy. The indirect cell viability evaluation and direct cell culture results indicated that the cytocompatibility of MC3T3-E1 cells on the Mg-1Ca alloy was improved by the ZnO layer on the surface.

チタンファイバー多孔質体に対する骨芽細胞様細胞の細胞適合性(大阪歯科大学大学院歯学研究科博士(歯学)学位論文内容要旨および論文審査結果要旨の公表)

チタンファイバー多孔質体に対する骨芽細胞様細胞の細胞適合性(大阪歯科大学大学院歯学研究科博士(歯学)学位論文内容要旨および論文審査結果要旨の公表)

Improvement of in vitro corrosion and cytocompatibility of biodegradable Fe surface modified by Zn ion implantation

Pure Fe was surface-modified by Zn ion implantation to improve the biodegradable behavior and cytocompatibility. Surface topography, chemical composition, corrosion resistance and cytocompatibility were investigated. Atomic force microscopy, auger electron spectroscopy and X-ray photoelectron spectroscopy results showed that Zn was implanted into the surface of pure Fe in the depth of 40–60nm and Fe2O3/ZnO oxides were formed on the outmost surface. Electrochemical measurements and immersion tests revealed an improved degradable behavior for the Zn-implanted Fe samples. An approximately 12% reduction in the corrosion potential (Ecorr) and a 10-fold increase in the corrosion current density (icorr) were obtained after Zn ion implantation with a moderate incident ion dose, which was attributed to the enhanced pitting corrosion. The surface free energy of pure Fe was decreased by Zn ion implantation. The results of direct cell culture indicated that the short-term (4h) cytocompatibility of MC3T3-E1 cells was promoted by the implanted Zn on the surface.

A biomimetic approach for enhancing adhesion and osteogenic differentiation of adipose-derived stem cells on poly(butylene succinate) composites with bioactive ceramics and glasses

The great potential application of poly(butylene succinate) (PBSu) as a novel biomaterial has not yet been realized, mainly owing to its insufficient bioactivity and low mechanical properties, which compromise the in vivo efficacy. Our strategy is based on the hypothesis that the incorporation of bioactive ceramics with similar microstructure to native bone structure into PBSu improves its bioactivity and affects new bone growth enhancing bone formation. Bioactive CaO–MgO–SiO2–Na2O–P2O5–CaF2 glass microparticles and fibrous hydroxyapatite nanoparticles were successfully synthesized and the resulting powders were characterized using different techniques. Afterwards, PBSu nanocomposites containing 2.5wt% of micro-Bioglass (mBG), nano-hydroxyapatite (nHA) or mBG-nHA were prepared via in situ polymerization and were studied thoroughly in terms of their physicochemical and biological properties. We show here that our strategy was effective in accelerating the in vitro biodegradability of PBSu, in enhancing apatite formation in contact with simulated body fluid (SBF), while inducing cytocompatibility and osteogenic differentiation of rat Adipose Stem Cells (rASCs).

对氨基苯甲酸掺杂的微槽结构碳纤维用于改善PLA-PEG的强度及生物相容性

Para-amino benzoic acid (PABA), a folic acid related metabolite, was first introduced to fabricate micro-grooves and improve hydrophilicity over surfaces of carbon fibers (CFs). Then, engineered CFs/poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) biocomposites were fabricated by a solvent casting/particulate leaching method. We found that introducing small hydrophobic PABA molecules and fabricating patterned structures would lead to benign integrated interfaces between CFs and the PLA-PEG matrix. Specifically, the compressive strength of CFs/PLA-PEG was improved from 3.98 to 5.48 MPa. In addition, the CFs/PLA-PEG biocomposites significantly accelerated the adhesion and proliferation of pre-osteoblasts with minimized cytotoxicity. By comparing the cyto-compatibility of L929 and MC3T3 cells cultured on different modified PLA-PEG composites, it could be concluded that PABA-CFs not only overcame the limitation of poor strength of PLA-PEG, but also improved the cell growth. These results indicate that the PABA-CFs reinforced PLA-PEG biocomposites could be a potential alternative for tissue engineering scaffolds.

Cytocompatibility and early inflammatory response of human endothelial cells in direct culture with Mg-Zn-Sr alloys.

Magnesium (Mg) alloys specifically designed for biodegradable implant applications have been the focus of biomedical research since the early 2000s. Physicochemical properties of Mg alloys make these metallic biomaterials excellent candidates for temporary biodegradable implants in orthopedic and cardiovascular applications. As Mg alloys continue to be investigated for biomedical applications, it is necessary to understand whether Mg-based materials or the alloying elements have the intrinsic ability to direct an immune response to improve implant integration while avoiding cell-biomaterial interactions leading to chronic inflammation and/or foreign body reactions. The present study utilized the direct culture method to investigate for the first time the in vitro transient inflammatory activation of endothelial cells induced by the degradation products of Zn-containing Mg alloys.

Synthesis and characterization of biocompatible antimicrobial N-halamine-functionalized titanium dioxide core-shell nanoparticles

As one of the most powerful biocides, N-halamine based antimicrobial materials have attracted much interest due to their non-toxicity, rechargeability, and rapid inactivation against a broad range of microorganisms. In this study, novel titanium dioxide-ADMH core-shell nanoparticles [TiO2@poly (ADMH-co-MMA) NPs] were prepared via miniemulsion polymerization using 3-allyl-5,5-dimethylhydantoin (ADMH) and methyl methacrylate (MMA) with nano-TiO2. The produced nanoparticles were characterized by FT-IR, TEM, TGA, and XPS. The UV stability of N-halamine nanoparticles has been improved with the addition of titanium dioxide. After chlorination treatment by sodium hypochlorite, biocidal efficacies of the chlorinated nanoparticles against S. aureus (ATCC 6538) and E. coli O157:H7 (ATCC 43895) were determined. The nanoparticles showed excellent antimicrobial properties against bacteria within brief contact time. In addition, in vitro cell cytocompatibility tests showed that the antibacterial nanoparticles had good biocompatibility.

New Visible-Light Photoinitiating System for Improved Print Fidelity in Gelatin-Based Bioinks.

Oxygen inhibition is a phenomenon that directly impacts the print fidelity of 3D biofabricated and photopolymerized hydrogel constructs. It typically results in the undesirable physical collapse of fabricated constructs due to impaired cross-linking, and is an issue that generally remains unreported in the literature. In this study, we describe a systematic approach to minimizing oxygen inhibition in photopolymerized gelatin-methacryloyl (Gel-MA)-based hydrogel constructs, by comparing a new visible-light initiating system, Vis + ruthenium (Ru)/sodium persulfate (SPS) to more conventionally adopted ultraviolet (UV) + Irgacure 2959 system. For both systems, increasing photoinitiator concentration and light irradiation intensity successfully reduced oxygen inhibition. However, the UV + I2959 system was detrimental to cells at both high I2959 concentrations and UV light irradiation intensities. The Vis + Ru/SPS system yielded better cell cyto-compatibility, where encapsulated cells remained >85% viable even at high Ru/SPS concentrations and visible-light irradiation intensities for up to 21 days, further highlighting the potential of this system to biofabricate cell-laden constructs with high shape fidelity, cell viability, and metabolic activity.

Cytocompatibility of HeLa Cells to Nano-Sized Ceramics Particles.

In this study, we investigated the behaviors and cytocompatibility response of human cervical carcinoma (HeLa) cells expose to nano-sized particles. Cultivated cells exposed to titanium oxide and indium oxide nanoparticles remained highly viable. In the presence of copper oxide (CuO); however, the cells became seriously inflamed. To understand the mechanism by which CuO causes cell death, we evaluated cell death and apoptosis cytometry. CuO induced cells apoptosis more strongly than exposure to titania nanoparticles. Confocal fluorescence microscopy revealed that the nano-sized particles penetrate the cells.

Fabrication and characterization of electrospun zein/Ag nanocomposite mats for wound dressing applications

Wound dressing is a very important factor in the process of wound healing as proper wound care can accelerate the recovery of the wound. In this study, zein nanofibrous mats with fiber diameters around 350–500nm were prepared by electrospinning and silver (Ag) nanoparticles around 20nm were concurrently synthesized in situ into the mats. The electrospun nanofibers were characterized by Field Emission-Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis. Cell viability and activity of fibroblasts cells in zein/Ag mats were also evaluated and results demonstrated good cytocompatibility and attachment of cells on the composite nanofibers. Also, the bactericidal activity of the fabricated mats against gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli) was investigated via zone of inhibition test and results showed high anti-bacterial performance.

Characterization and cytocompatibility of a new injectable multiphasic bone substitute based on a combination of polysaccharide gel-coated OSPROLIFE(®) HA/TTCP granules and bone marrow concentrate.

The purpose of this study was to examine the in vitro cytocompatibility of a novel injectable multiphasic bone substitute (MBS) based on polysaccharide gel-coated OSPROLIFE(®) hydroxyapatite (HA)/tetracalcium phosphate (TTCP) granules combined with bone marrow concentrate (BMC). Polysaccharide gel-coated granules loaded in syringe were combined with BMC diluted in ionic crosslinking solution. The product was then maintained in culture to investigate the cytocompatibility, distribution, and osteogenic differentiation function of cells contained in the BMC. The in vitro cytocompatibility was assessed after 0, 24, and 96 h from the injectable MBS preparation using the LIVE/DEAD(®) staining kit. The results highlighted that cells remained viable after combination with the polysaccharide gel-coated granules; also, viability was maintained over time. The distribution of the cells in the product, observed using confocal microscopy, showed viable cells immersed in the polysaccharide gel formed between the granules after ionic crosslinking. The mesenchymal stromal cells (MSC) contained in the injectable MBS, the basic elements for bone tissue regeneration, were able to differentiate toward osteoblasts, producing an osteogenic matrix as evidenced by alizarin red-s (AR-S) staining. In conclusion, we found that the injectable MBS may have the potential to be used as a bone substitute by applying a "one-step" procedure in bone tissue engineering applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 894-902, 2016.

Influence of ethanol content in the precipitation medium on the composition, structure and reactivity of magnesium-calcium phosphate.

Biocompatible amorphous magnesium calcium phosphate (AMCP) particles were synthesized using ethanol in precipitation medium from moderately supersaturated solution at pH10. Some synthesis parameters such as, (Mg+Ca):P, Mg:Ca ratio and different drying methods on the structure and stability of as-produced powder was studied and characterized using SEM, XRD and cell cytocompatibility. The results showed that depending on the Mg(2+) concentration, nano crystalline Struvite (MgNH4PO4·6H2O) can also be alternatively formed. However, the as-formed AMCP preserved its amorphous structure after 7 days of incubation in SBF for tested phosphate concentration, and equally ionic concentration of magnesium and calcium.