Correction: Hung et al. Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells. Int. J. Mol. Sci. 2021, 22, 9262.

The authors wish to make the following correction to this paper [...].

Evaluation of the Biocompatibility and Endothelial Differentiation Capacity of Mesenchymal Stem Cells by Polyethylene Glycol Nanogold Composites.

Cardiovascular Diseases (CVDs) such as atherosclerosis, where inflammation occurs in the blood vessel wall, are one of the major causes of death worldwide. Mesenchymal Stem Cells (MSCs)-based treatment coupled with nanoparticles is considered to be a potential and promising therapeutic strategy for vascular regeneration. Thus, angiogenesis enhanced by nanoparticles is of critical concern. In this study, Polyethylene Glycol (PEG) incorporated with 43.5 ppm of gold (Au) nanoparticles was prepared for the evaluation of biological effects through in vitro and in vivo assessments. The physicochemical properties of PEG and PEG-Au nanocomposites were first characterized by UV-Vis spectrophotometry (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and Atomic Force Microscopy (AFMs). Furthermore, the reactive oxygen species scavenger ability as well as the hydrophilic property of the nanocomposites were also investigated. Afterwards, the biocompatibility and biological functions of the PEG-Au nanocomposites were evaluated through in vitro assays. The thin coating of PEG containing 43.5 ppm of Au nanoparticles induced the least platelet and monocyte activation. Additionally, the cell behavior of MSCs on PEG-Au 43.5 ppm coating demonstrated better cell proliferation, low ROS generation, and enhancement of cell migration, as well as protein expression of the endothelialization marker CD31, which is associated with angiogenesis capacity. Furthermore, anti-inflammatory and endothelial differentiation ability were both evaluated through in vivo assessments. The evidence demonstrated that PEG-Au 43.5 ppm implantation inhibited capsule formation and facilitated the expression of CD31 in rat models. TUNEL assay also indicated that PEG-Au nanocomposites would not induce significant cell apoptosis. The above results elucidate that the surface modification of PEG-Au nanomaterials may enable them to serve as efficient tools for vascular regeneration grafts.

Engineered Pullulan-Collagen-Gold Nano Composite Improves Mesenchymal Stem Cells Neural Differentiation and Inflammatory Regulation.

Tissue repair engineering supported by nanoparticles and stem cells has been demonstrated as being an efficient strategy for promoting the healing potential during the regeneration of damaged tissues. In the current study, we prepared various nanomaterials including pure Pul, pure Col, Pul-Col, Pul-Au, Pul-Col-Au, and Col-Au to investigate their physicochemical properties, biocompatibility, biological functions, differentiation capacities, and anti-inflammatory abilities through in vitro and in vivo assessments. The physicochemical properties were characterized by SEM, DLS assay, contact angle measurements, UV-Vis spectra, FTIR spectra, SERS, and XPS analysis. The biocompatibility results demonstrated Pul-Col-Au enhanced cell viability, promoted anti-oxidative ability for MSCs and HSFs, and inhibited monocyte and platelet activation. Pul-Col-Au also induced the lowest cell apoptosis and facilitated the MMP activities. Moreover, we evaluated the efficacy of Pul-Col-Au in the enhancement of neuronal differentiation capacities for MSCs. Our animal models elucidated better biocompatibility, as well as the promotion of endothelialization after implanting Pul-Col-Au for a period of one month. The above evidence indicates the excellent biocompatibility, enhancement of neuronal differentiation, and anti-inflammatory capacities, suggesting that the combination of pullulan, collagen, and Au nanoparticles can be potential nanocomposites for neuronal repair, as well as skin tissue regeneration in any further clinical treatments.

Inflammatory Modulation of Polyethylene Glycol-AuNP for Regulation of the Neural Differentiation Capacity of Mesenchymal Stem Cells.

A nanocomposite composed of polyethylene glycol (PEG) incorporated with various concentrations (~17.4, ~43.5, ~174 ppm) of gold nanoparticles (Au) was created to investigate its biocompatibility and biological performance in vitro and in vivo. First, surface topography and chemical composition was determined through UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), free radical scavenging ability, and water contact angle measurement. Additionally, the diameters of the PEG-Au nanocomposites were also evaluated through dynamic light scattering (DLS) assay. According to the results, PEG containing 43.5 ppm of Au demonstrated superior biocompatibility and biological properties for mesenchymal stem cells (MSCs), as well as superior osteogenic differentiation, adipocyte differentiation, and, particularly, neuronal differentiation. Indeed, PEG-Au 43.5 ppm induced better cell adhesion, proliferation and migration in MSCs. The higher expression of the SDF-1α/CXCR4 axis may be associated with MMPs activation and may have also promoted the differentiation capacity of MSCs. Moreover, it also prevented MSCs from apoptosis and inhibited macrophage and platelet activation, as well as reactive oxygen species (ROS) generation. Furthermore, the anti-inflammatory, biocompatibility, and endothelialization capacity of PEG-Au was measured in a rat model. After implanting the nanocomposites into rats subcutaneously for 4 weeks, PEG-Au 43.5 ppm was able to enhance the anti-immune response through inhibiting CD86 expression (M1 polarization), while also reducing leukocyte infiltration (CD45). Moreover, PEG-Au 43.5 ppm facilitated CD31 expression and anti-fibrosis ability. Above all, the PEG-Au nanocomposite was evidenced to strengthen the differentiation of MSCs into various cells, including fat, vessel, and bone tissue and, particularly, nerve cells. This research has elucidated that PEG combined with the appropriate amount of Au nanoparticles could become a potential biomaterial able to cooperate with MSCs for tissue regeneration engineering.

Physical Gold Nanoparticle-Decorated Polyethylene Glycol-Hydroxyapatite Composites Guide Osteogenesis and Angiogenesis of Mesenchymal Stem Cells.

In this study, polyethylene glycol (PEG) with hydroxyapatite (HA), with the incorporation of physical gold nanoparticles (AuNPs), was created and equipped through a surface coating technique in order to form PEG-HA-AuNP nanocomposites. The surface morphology and chemical composition were characterized using scanning electron microscopy (SEM), atomic force microscopy (AFM), UV-Vis spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and contact angle assessment. The effects of PEG-HA-AuNP nanocomposites on the biocompatibility and biological activity of MC3T3-E1 osteoblast cells, endothelial cells (EC), macrophages (RAW 264.7), and human mesenchymal stem cells (MSCs), as well as the guiding of osteogenic differentiation, were estimated through the use of an in vitro assay. Moreover, the anti-inflammatory, biocompatibility, and endothelialization capacities were further assessed through in vivo evaluation. The PEG-HA-AuNP nanocomposites showed superior biological properties and biocompatibility capacity for cell behavior in both MC3T3-E1 cells and MSCs. These biological events surrounding the cells could be associated with the activation of adhesion, proliferation, migration, and differentiation processes on the PEG-HA-AuNP nanocomposites. Indeed, the induction of the osteogenic differentiation of MSCs by PEG-HA-AuNP nanocomposites and enhanced mineralization activity were also evidenced in this study. Moreover, from the in vivo assay, we further found that PEG-HA-AuNP nanocomposites not only facilitate the anti-immune response, as well as reducing CD86 expression, but also facilitate the endothelialization ability, as well as promoting CD31 expression, when implanted into rats subcutaneously for a period of 1 month. The current research illustrates the potential of PEG-HA-AuNP nanocomposites when used in combination with MSCs for the regeneration of bone tissue, with their nanotopography being employed as an applicable surface modification approach for the fabrication of biomaterials.

Delivery Capacity and Anticancer Ability of the Berberine-Loaded Gold Nanoparticles to Promote the Apoptosis Effect in Breast Cancer.

Gold nanoparticles (AuNPs) were fabricated with biocompatible collagen (Col) and then conjugated with berberine (BB), denoted as Au-Col-BB, to investigate the endocytic mechanisms in Her-2 breast cancer cell line and in bovine aortic endothelial cells (BAEC). Owing to the superior biocompatibility, tunable physicochemical properties, and potential functionalization with biomolecules, AuNPs have been well studied as carriers of biomolecules for diseases and cancer therapeutics. Composites of AuNPs with biopolymer, such as fibronectin or Col, have been revealed to increase cell proliferation, migration, and differentiation. BB is a natural compound with impressive health benefits, such as lowering blood sugar and reducing weight. In addition, BB can inhibit cell proliferation by modulating cell cycle progress and autophagy, and induce cell apoptosis in vivo and in vitro. In the current research, BB was conjugated on the Col-AuNP composite ("Au-Col"). The UV-Visible spectroscopy and infrared spectroscopy confirmed the conjugation of BB on Au-Col. The particle size of the Au-Col-BB conjugate was about 227 nm, determined by dynamic light scattering. Furthermore, Au-Col-BB was less cytotoxic to BAEC vs. Her-2 cell line in terms of MTT assay and cell cycle behavior. Au-Col-BB, compared to Au-Col, showed greater cell uptake capacity and potential cellular transportation by BAEC and Her-2 using the fluorescence-conjugated Au-Col-BB. In addition, the clathrin-mediated endocytosis and cell autophagy seemed to be the favorite endocytic mechanism for the internalization of Au-Col-BB by BAEC and Her-2. Au-Col-BB significantly inhibited cell migration in Her-2, but not in BAEC. Moreover, apoptotic cascade proteins, such as Bax and p21, were expressed in Her-2 after the treatment of Au-Col-BB. The tumor suppression was examined in a model of xenograft mice treated with Au-Col-BB nanovehicles. Results demonstrated that the tumor weight was remarkably reduced by the treatment of Au-Col-BB. Altogether, the promising findings of Au-Col-BB nanocarrier on Her-2 breast cancer cell line suggest that Au-Col-BB may be a good candidate of anticancer drug for the treatment of human breast cancer.

Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells.

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton's jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1ß, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials.

Evaluation of Polyvinyl Alcohol/Cobalt Substituted Hydroxyapatite Nanocomposite as a Potential Wound Dressing for Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) caused by diabetes are prone to serious and persistent infections. If not treated properly, it will cause tissue necrosis or septicemia due to peripheral blood vessel embolism. Therefore, it is an urgent challenge to accelerate wound healing and reduce the risk of bacterial infection in patients. In clinical practice, DFUs mostly use hydrogel dressing to cover the surface of the affected area as an auxiliary treatment. Polyvinyl alcohol (PVA) is a hydrophilic hydrogel polymer widely used in dressings, drug delivery, and medical applications. However, due to its weak bioactivity and antibacterial ability, leads to limited application. Filler adding is a useful way to enhance the biocompatibility of PVA. In our study, cobalt-substituted hydroxyapatite (CoHA) powder was prepared by the electrochemically-deposited method. PVA and PVA-CoHA nanocomposite were prepared by the solvent casting method. The bioactivity of the PVA and composite was evaluated by immersed in simulated body fluid for 7 days. In addition, L929 cells and E. coli were used to evaluate the cytotoxicity and antibacterial tests of PVA and PVA-CoHA nanocomposite. The results show that the addition of CoHA increases the mechanical properties and biological activity of PVA. Biocompatibility evaluation showed no significant cytotoxicity of PVA-CoHA composite. In addition, a small amount of cobalt ion was released to the culture medium from the nanocomposite in the cell culture period and enhanced cell growth. The addition of CoHA also confirmed that it could inhibit the growth of E. coli. PVA-CoHA composite may have potential applications in diabetic trauma healing and wound dressing.

Duchesnea indica extract attenuates oral cancer cells metastatic potential through the inhibition of the matrix metalloproteinase-2 activity by down-regulating the MEK/ERK pathway.

BACKGROUND: Duchesnea indica (Andr.) Focke, an herb in folk medicine used extensively in traditional Chinese medicine, has cytostatic properties as well as antioxidant and antimetastasis activities in various cancer cells. However, the effects and underlying mechanisms of Duchesnea indica extracts (DIEs) on human oral squamous cell carcinoma (OSCC) metastases remain unclear. PURPOSE: In this study, we posit the hypothesis that DIE possesses antimetastatic effects on human OSCC cells. METHODS: The effects of DIE on cell viability, motility, migration, and invasion were investigated. Gelatin zymography, Western blotting, migration and invasion assays were used to further study the underlying mechanisms involved in the antimetastatic effects of DIE in OSCC cells. RESULTS: The results from MTT assay revealed that DIE did not affect the cell viability of OSCC cells. Moreover, DIE significantly attenuated OSCC cells' motility, migration, and invasion by reducing the MMP-2 protein expression and MMP-2 activity in a dose-dependent manner. In addition, DIE reduced the phosphorylation of both ERK1/2 and its upstream kinase but had no effect on the phosphorylation of p38 and JNK. CONCLUSION: DIE triggers the antimetastatic activity in OSCC cells by suppressing the MMP-2 activity via the MEK/ERK signaling pathways. Therefore, these findings are promising for the use of DIE antimetastatic activity in oral cancer metastasis treatment.

Licochalcone A induces apoptotic cell death via JNK/p38 activation in human nasopharyngeal carcinoma cells.

Licochalcone A is widely studied in different fields and possesses antiasthmatic, antibacterial, anti-inflammatory, antioxidative, and anticancer properties. Its antimalignancy activity on renal, liver, lung, and oral cancer has been explored. However, limited studies have been conducted on the inhibitory effects of licochalcone A in human nasopharyngeal carcinoma cells. We determined cell viability using MTT assay. Cell cycle distribution and apoptotic cell death were measured via flow cytometry. Caspase activation and mitogen-activated protein kinase-related proteins in nasopharyngeal cancer cells in response to licochalcone A were identified by Western blot analysis. Results indicated that licochalcone A reduces cell viability and induces apoptosis, as evidenced by the upregulation of caspase-8 and caspase-9, caspase-3 activation, and cleaved-poly ADP-ribose polymerase expression. Treatment with licochalcone A significantly increases ERK1/2, p38, and JNK1/2 activation. Co-administration of a JNK inhibitor (JNK-IN-8) or p38 inhibitor (SB203580) abolishes the activation of caspase-9, caspase-8, and caspase-3 protein expression during licochalcone A treatment. These findings indicate that licochalcone A exerts a cytostatic effect through apoptosis by targeting the JNK/p38 pathway in human nasopharyngeal carcinoma cells. Therefore, licochalcone A is a promising therapeutic agent for the treatment of human nasopharyngeal cancer cells.

Long-term in vitro degradation behavior and biocompatibility of polycaprolactone/cobalt-substituted hydroxyapatite composite for bone tissue engineering.

OBJECTIVE: Currently, infections due to foreign-body reactions caused by bacteria or implant materials at the wound site are one of the major reasons for the failure of guided tissue regeneration (GTR) and guided bone regeneration (GBR) in clinical applications. The purpose of this study was to develop regeneration membranes with localized cobalt ion release to reduce infection and inflammation by polycaprolactone (PCL)/cobalt-substituted hydroxyapatite (CoHA). METHODS: The PCL composite membrane containing 20 wt% CoHA powders was prepared by solvent casting. The surface morphology, crystal structure, chemical composition and thermal properties of PCL composite membranes were characterized. The biocompatibility, osteogenic differentiation and antibacterial properties of composite membrane were also investigated. Then, in biodegradability was assessed by immersing phosphate buffer solution (PBS) for 6 months. RESULTS: Physicochemical analyses revealed that CoHA is evenly mixed in the membranes and assistance reduce the crystallinity of PCL for getting more degradation amounts than PCL membrane. Osteoblast cells culture on the membrane showed that the CoHA significantly increases cell proliferation and found the calcium deposition production increased over 90% compared with PCL after 7 days of culture. A good antibacterial effect was achieved by the addition of CoHA powder. The results were confirmed by 2.4 times reduction of proliferation of Escherichia coli (E. coli) seeded on the composite membrane after 24 h. Immersing in PBS for 6 months indicated that PCL-CoHA composite membrane has improved biodegradation and can continuously remove free radicals to reduce the inflammatory response. SIGNIFICANCE: The PCL-CoHA composite membrane with suitable releasing of cobalt ion can be considered as a potential choice for bone tissue regeneration.

The Effect of Electrode Topography on the Magnetic Properties and MRI Application of Electrochemically-Deposited, Synthesized, Cobalt-Substituted Hydroxyapatite.

Magnetic nanoparticles are used to enhance the image contrast of magnetic resonance imaging (MRI). However, the development of magnetic nanoparticles with a low dose/high image contrast and non-toxicity is currently a major challenge. In this study, cobalt-substituted hydroxyapatite nanoparticles deposited on titanium (Ti-CoHA) and cobalt-substituted hydroxyapatite nanoparticles deposited on titanium dioxide nanotubes (TNT-CoHA) were synthesized by the electrochemical deposition method. The particle sizes of Ti-CoHA and TNT-CoHA were 418.6 nm and 127.5 nm, respectively, as observed using FE-SEM. It was shown that CoHA can be obtained with a smaller particle size using a titanium dioxide nanotube (TNT) electrode plate. However, the particle size of TNT-CoHA is smaller than that of Ti-CoHA. The crystal size of the internal cobalt oxide of CoHA was calculated by using an XRD pattern. The results indicate that the crystal size of cobalt oxide in TNT-CoHA is larger than that of the cobalt oxide in Ti-CoHA. The larger crystal size of the cobalt oxide in TNT-CoHA makes the saturation magnetization (Ms) of TNT-CoHA 12.6 times higher than that of Ti-CoHA. The contrast in MRIs is related to the magnetic properties of the particles. Therefore, TNT-CoHA has good image contrast at low concentrations in T2 images. The relaxivity coefficient of the CoHA was higher for TNT-CoHA (340.3 mM-1s-1) than Ti-CoHA (211.7 mM-1s-1), and both were higher than the commercial iron nanoparticles (103.0 mM-1s-1). We showed that the TNT substrate caused an increase in the size of the cobalt oxide crystal of TNT-CoHA, thus effectively improving the magnetic field strength and MRI image recognition. It was also shown that the relaxivity coefficient rose with the Ms. Evaluation of biocompatibility of CoHA using human osteosarcoma cells (MG63) indicated no toxic effects. On the other hand, CoHA had an excellent antibacterial effect, as shown by E. coli evaluation, and the effect of TNT-CoHA powder was higher than that of Ti-CoHA powder. In summary, TNT-CoHA deposited electrochemically on the TNT substrates can be considered as a potential candidate for the application as an MRI contrast agent. This paper is a comparative study of how different electrode plates affect the magnetic and MRI image contrast of cobalt-substituted hydroxyapatite (CoHA) nanomaterials.

Functional engineered mesenchymal stem cells with fibronectin-gold composite coated catheters for vascular tissue regeneration.

Vascularization of engineered tissues remains one of the key problems. Here, we described a novel approach to promote vascularization of engineered tissues using fibronectin (FN) incorporated gold nanoparticles (AuNP) coated onto catheters with mesenchymal stem cells (MSCs) for tissue engineering. We found that the FN-AuNP composite with 43.5 ppm of AuNP exhibited better biomechanical properties and thermal stability than pure FN. FN-AuNP composites promoted MSC proliferation and increased the biocompatibility. Mechanistically, vascular endothelial growth factor (VEGF) promoted MSC migration on FN-AuNP through the endothelial oxide synthase (eNOS)/metalloproteinase (MMP) signaling pathway. Vascular femoral artery tissues isolated from the implanted FN-AuNP-coated catheters with MSCs expressed substantial CD31 and alpha-smooth muscle actin (α-SMA), displayed higher antithrombotic activity, as well as better endothelialization ability than those coated with all other materials. These data suggested that the implantation of FN-AuNP-coated catheter with MSCs could be a novel strategy for vascular biomaterials applications.

A Comparative Study on the Direct and Pulsed Current Electrodeposition of Cobalt-Substituted Hydroxyapatite for Magnetic Resonance Imaging Application.

Hydroxyapatite has excellent biocompatibility and osteo-conductivity and, as the main inorganic component of human bones and teeth, is commonly used for bone repair. Its original characteristics can be changed by metal ion substitution. Cobalt ions can act as hypoxia-inducible factors and accelerate bone repair. At the same time, cobalt has paramagnetic properties and is often used in the study of medical imaging and target drugs. Through the introduction of cobalt ions, the unique hydroxyapatite has better biological activity and positioning of medical images. Herein, cobalt-substituted hydroxyapatite (CoHA) was synthesized on the surface of a titanium plate by electrochemical deposition and changes in the power output mode to explore the impact on CoHA. Electrochemical deposition with a pulse current significantly improved the productivity and uniformity of CoHA on the surface of titanium. CoHA show paramagnetic characteristics by a superconducting quantum interference device (SQUID). Resulting smaller particle size and circular morphology improves the magnetic strength of CoHA. Magnetic resonance imaging (MRI) of CoHA showed significant image contrast effect at low concentrations. The calculated particle relaxation rate was higher than other common MRI contrast agents. Biocompatibility of CoHA powder was evaluated using the human osteosarcoma cell line (MG63) which confirmed that CoHA is not cytotoxic and can promote cell growth and extracellular matrix mineralization. With the release of cobalt ions, CoHA was found to be significantly good in repression E. coli indicating about than 95% reduction in bacterial growth. The as-synthesized CoHA has a low degree of crystallinity, highly sensitive image contrast effect, and good bioactivity, and may have potential applications in bone repair and MRI.

Prominent Vascularization Capacity of Mesenchymal Stem Cells in Collagen-Gold Nanocomposites.

The ideal characteristics of surface modification on the vascular graft for clinical application would be with excellent hemocompatibility, endothelialization capacity, and antirestenosis ability. Here, Fourier transform infrared spectroscopy (FTIR), surface enhanced Raman spectroscopy (SERS), atomic force microscopy (AFM), contact angle (θ) measurement, and thermogravimetric analysis (TGA) were used to evaluate the chemical and mechanical properties of collagen-gold nanocomposites (collagen+Au) with 17.4, 43.5, and 174 ppm of Au and suggested that the collagen+Au with 43.5 ppm of Au had better biomechanical properties and thermal stability than pure collagen. Besides, stromal-derived factor-1α (SDF-1α) at 50 ng/mL promoted the migration of mesenchymal stem cells (MSCs) on collagen+Au material through the α5ß3 integrin/endothelial oxide synthase (eNOS)/metalloproteinase (MMP) signaling pathway which can be abolished by the knockdown of vascular endothelial growth factor (VEGF). The potentiality of collagen+Au with MSCs for vascular regeneration was evaluated by our in vivo rat model system. Artery tissues isolated from an implanted collagen+Au-coated catheter with MSCs expressed substantial CD-31 and α-SMA, displayed higher antifibrotic ability, antithrombotic activity, as well as anti-inflammatory response than all other materials. Our results indicated that the implantation of collagen+Au-coated catheters with MSCs could be a promising strategy for vascular regeneration.

Poly(vinyl alcohol) Nanocomposites Reinforced with Bamboo Charcoal Nanoparticles: Mineralization Behavior and Characterization.

Polyvinyl alcohol (PVA) demonstrates chemical stability and biocompatibility and is widely used in biomedical applications. The porous bamboo charcoal has excellent toxin absorptivity and has been used in blood purification. In this study, bamboo charcoal nanoparticles (BCNPs) were acquired with nano-grinding technology. The PVA and PVA/BCNP nanocomposite membranes were prepared and characterized by the tensile test, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD). Results showed that the tensile strength and elongation of the swollen PVA membranes containing 1% BCNPs (PB1) were significantly greater than those of PVA and other PVA/BCNP composite membranes. In addition, the major absorption band of OH stretching in the IR spectra shifted from 3262 cm-¹ for PVA membrane containing 1% BCNP to 3244 cm-¹ for PVA membrane containing 20% BCNP. This blue shift might be attributed to the interaction between the PVA molecules and BCNPs. Moreover, the intensity of the XRD peaks in PVA was decreased with the increased BCNP content. The bioactivity of the nanocomposites was evaluated by immersion in the simulated body fluid (SBF) for seven days. The mineral deposition on PB5 was significantly more than that on the other samples. The mineral was identified as hydroxyapatite (HA) by XRD. These data suggest that the bioactivity of the composite hydrogel membranes was associated with the surface distribution of hydrophilic/hydrophobic components. The PVA/BCNP composite hydrogels may have potential applications in alveolar bone regeneration.

In vitro study of a novel nanogold-collagen composite to enhance the mesenchymal stem cell behavior for vascular regeneration.

Novel nanocomposites based on type I collagen (Col) containing a small amount (17.4, 43.5, and 174 ppm) of gold nanoparticles (AuNPs, approximately 5 nm) were prepared in this study. The pure Col and Col-AuNP composites (Col-Au) were characterized by the UV-Vis spectroscopy (UV-Vis), surface-enhanced raman spectroscopy (SERS) and atomic force microscopy (AFM). The interaction between Col and AuNPs was confirmed by infrared (IR) spectra. The effect of AuNPs on the biocompatibility of Col, evaluated by the proliferation and reactive oxygen species (ROS) production of mesenchymal stem cells (MSCs) as well as the activation of monocytes and platelets, was investigated. Results showed that Col-Au had better biocompatibility than Col. Upon stimulation by vascular endothelial growth factor (VEGF) and stromal derived factor-1α (SDF-1α), MSCs expressed the highest levels of αvß3 integrin/CXCR4, focal adhesion kinase (FAK), matrix metalloproteinase-2 (MMP-2), and Akt/endothelial nitric oxide synthase (eNOS) proteins when grown on the Col-Au (43.5 ppm) nanocomposite. Taken together, Col-Au nanocomposites may promote the proliferation and migration of MSCs and stimulate the endothelial cell differentiation. These results suggest that Col-Au may be used to construct tissue engineering scaffolds for vascular regeneration.

Biocompatibility and favorable response of mesenchymal stem cells on fibronectin-gold nanocomposites.

A simple surface modification method, comprising of a thin coating with gold nanoparticles (AuNPs) and fibronectin (FN), was developed to improve the biocompatibility required for cardiovascular devices. The nanocomposites from FN and AuNPs (FN-Au) were characterized by the atomic force microscopy (AFM), UV-Vis spectrophotometry (UV-Vis), and Fourier transform infrared spectroscopy (FTIR). The biocompatibility of the nanocomposites was evaluated by the response of monocytes and platelets to the material surface in vitro. FN-Au coated surfaces demonstrated low monocyte activation and platelet activation. The behavior of human umbilical cord-derived mesenchymal stem cells (MSCs) on FN-Au was further investigated. MSCs on FN-Au nanocomposites particularly that containing 43.5 ppm of AuNPs (FN-Au 43.5 ppm) showed cell proliferation, low ROS generation, as well as increases in the protein expression levels of matrix metalloproteinase-9 (MMP-9) and endothelial nitric oxide synthase (eNOS), which may account for the enhanced MSC migration on the nanocomposites. These results suggest that the FN-Au nanocomposite thin film coating may serve as a potential and simple solution for the surface modification of blood-contacting devices such as vascular grafts.

Comparison between two different methods of immobilizing NGF in poly(DL-lactic acid-co-glycolic acid) conduit for peripheral nerve regeneration by EDC/NHS/MES and genipin.

For surface modification and nerve regeneration, chitosan, followed by nerve growth factor (NGF), was immobilized onto the interior surface of poly (lactic acit-co-glycolic) conduits, using EDC/NHS/MES system (EDCs) and genipin (GP). Four new conduits were, therefore, obtained and named by immobilizing order-EDCs/EDCs, GP/EDCs, EDCs/GP, and GP/GP groups. The immobilized methods used were evaluated and compared, respectively. The researchers found that the EDCs- and GP-cross-linked chitosan displayed higher hydrophilic than pure poly (DL-lactic acid-co-glycolic acid) (PLGA) in water contact angle experiment, which meant the cell compatibility was improved by the modification. Scanning electron microscopic observations revealed that the GP-cross-linking of chitosan greatly improved cell compatibility while cultured rat PC12 cells were flatter and more spindle-shaped than EDCs-cross-linked chitosan. The results concerning the GP-cross-linked chitosan revealed significant proliferation of the seeded cells relative to pure PLGA films, as determined by counting cells and MTT assay. The NGF was released from the modified conduits in two separate periods--an initial burst in 5 days and then slow release from day 10 to day 40. The GP/EDCs group had the highest NGF value among all groups after the 5th day. Finally, the controlled-release conduits were used to bridge a 10 mm rat sciatic nerve defect. Six weeks following implantation, morphological analysis revealed the highest numbers of myelinated axons in the midconduit and distal regenerated nerve in GP/EDCs group. Therefore, the results confirm that GP/EDCs groups with good cell compatibility and effective release of NGF can considerably improve peripheral nerve regeneration.

Biostability and biocompatibility of poly(ester urethane)-gold nanocomposites.

Nanocomposites from a polyester-type water-borne polyurethane (PU) containing different amounts (17.4-174 ppm) of gold (Au) nanoparticles (approximately 5 nm) were prepared. A previous study has shown that the Au nanoparticles could induce surface morphological transformations in the PU (e.g. the mesophase transition from hard lamellae to soft micelles), which modify the physicochemical properties of the PU as well as the fibroblast response to the PU. The current study focused on the biostability and biocompatibility of the nanocomposites. The nanocomposites were characterized by transmission electron microscopy and X-ray photoelectron spectroscopy, and their oxidative stability and free radical scavenging ability were tested. The inflammatory response was evaluated by monocyte activation in vitro and rat subcutaneous implantation in vivo. It was found that the nanocomposites containing 43.5-65 ppm of Au had the least monocyte activation and tissue reactions. PU and the nanocomposites were rather resistant to oxidative degradation in vitro and biodegradation in vivo. The nanocomposites exhibited greater free radical scavenging abilities than the original PU. Based on the above results, the significantly enhanced biocompatibility of the PU-Au nanocomposites with 43.5-65 ppm of gold over the original PU appeared to be a result of the extensively modified surface morphology and greater free radical scavenging ability, instead of due to the difference in biostability.