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Nanomaterials (NMs) with tubular structures, such as halloysite nanotubes (HNTs), have potential applications in biomedicine. Although the biocompatibility of HNTs has been investigated before, the toxicity of HNTs to blood vessels is rarely systemically evaluated. Herein, we compared the toxicity of HNTs and multi-walled carbon nanotubes (MWCNTs) to human umbilical vein endothelial cells (HUVECs) in vitro and blood vessels of mice in vivo. HUVECs internalized HNTs and MWCNTs, but the uptake of HNTs was not obviously changed by clathrin inhibitor. Exposure to NMs decreased cellular viability, activated apoptotic proteins and up-regulated adhesion molecules, including soluble vascular cell adhesion molecule 1 (sVCAM-1) and VCAM-1. As the mechanisms, NMs decreased NO levels, eNOS mRNA and eNOS/p-eNOS proteins. Meanwhile, NMs promoted intracellular ROS and autophagy dysfunction, shown as decreased protein levels of LC3, beclin-1 and ATG5. The eNOS regulator Kruppel-like factor 4 (KLF4) was inhibited, but another eNOS regulator KLF4 was surprisingly up-regulated. Under in vivo conditions, ICR mice intravenously injected with NMs (50 μg/mouse, once a day for 5 days) showed an increased percentage of neutrophils, monocytes and basophils. Meanwhile, autophagy dysfunction, eNOS uncoupling, activation of apoptotic proteins and alteration of KLF proteins were also observed in mouse aortas. All of the toxic effects were more pronounced for MWCNTs in comparison with HNTs based on the same mass concentrations. Our results may provide novel insights about the toxicity of NMs with tubular structures to blood vessels. Considering the toxicological data reported here, HNTs are probably safer nanocarriers compared with MWCNTs. [ABSTRACT FROM AUTHOR]

The design of porous tissue engineering scaffold with multiscale open-pore architecture (i.e. , bimodal structure) promotes cell attachment and growth, which facilitates nutrient and oxygen diffusion. In this study, a porous poly (butylene succinate) (PBS)/cellulose nanocrystals (CNCs) composite scaffold with a well-defined controllable bimodal open-pore interconnected structure was successfully fabricated. The bimodal open-porous scaffold architecture was designed by synergistic control of temperature variation and a two-step depressurization in a supercritical carbon dioxide (Sc-CO 2) foaming process. The microstructure and properties of the bimodal open-porous PBS/CNCs scaffold, such as morphology, open porosity, hydrophilic and degradation performance, and mechanical compression properties, were analyzed. In the experiments, the scaffold with unimodal pore structure was used for comparison. The results showed that the bimodal open-porous PBS5 scaffold displayed a well-defined bimodal open-pore structure composed of large pore (~68.9 μm in diameter) and small pore (~11.0 μm in diameter), with a high open porosity (~95.2%). In addition, the scaffolds exhibited good mechanical compressive properties (compressive strength of 2.76 MPa at 50% strain), hydrophilicity (water contact angle of 71.7 °C) and in vitro degradation rate. Moreover, in vitro biocompatibility was determined with NIH-3T3 fibroblast cells using MTT assay and live/dead cell viability assay. Results indicated that the obtained bimodal open-porous scaffolds had a good biocompatibility and the viability of cells grown on the scaffolds reached up to 98% after 7th day of culture. Therefore, our work provides new insights into the use of biodegradable polymeric composite scaffolds with bimodal open-pore structure and balanced properties in tissue engineering. [ABSTRACT FROM AUTHOR]

To improve the mechanical properties and biocompatibility of collagen I matrix, a novel and facile strategy was developed to modify porcine acellular dermal matrix (PADM) via dopamine self-polymerization followed by collagen immobilization to enhance the biological, mechanical and physicochemical properties of PADM. Mechanism study indicated that the polymerization of dopamine onto PADM surface could be regulated by controlling the amount of hydrogen bonds forming between phenol hydroxyl (C OH) and nitrogen atom (N C O) within collagen fibers of PADM. The investigations of surface interactions between PDA and PADM illustrated that PDA-PADM system yielded better mechanical properties, thermal stability, surface hydrophilicity and the structural integrity of PADM was maintained after dopamine coating. Furthermore, collagen (COL) was immobilized onto the fresh PDA-PADM to fabricate the collagen-PDA-PADM (COL-PDA-PADM) complexed scaffold. The MTT assay and CLSM observation showed that COL-PDA-PADM had better biocompatibility and higher cellular attachment than pure PADM and COL-PADM without dopamine coating, thus demonstrating the efficacy of PDA as the intermediate layer. Meanwhile, the expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) of COL-PDA-PADM were investigated by an in vivo study. The results revealed that COL-PDA-PADM could effectively promote bFGF and VEGF expression, possibly leading to enhancing the dura repairing process. Overall, this work contributed a new insight into the development of a semi-natural tissue engineering scaffold with high biocompatibility and good mechanical properties. Statement of Significance Obtaining scaffolds with high biocompatibility and good mechanical properties is still one of the most challenging issues in tissue engineering. To have excellent in vitro and in vivo performance, scaffolds are desired to have similar mechanical and biological properties as the natural extracellular matrix, such as collagen based matrix. Utilizing the surface self-crosslinking and coating strategy, we successfully obtained a novel semi-natural platform with excellent biological and mechanical properties from porcine acellular dermal matrix (PADM), polydopamine and collagen. The results confirmed that this scaffold platform has very excellent cellular performance and very little toxicity/side effects in vivo . Therefore, this semi-natural scaffold may be an appropriate platform for tissue engineering and this strategy would further help to develop more robust scaffolds. [ABSTRACT FROM AUTHOR]

ABSTRACT Porcine acellular dermal matrix (PADM) has been investigated widely as a natural biomaterial. However, the success of PADM has been limited by insufficient stability and poor physicochemical properties. In our work, alginate dialdehyde (ADA) with various oxidation degrees (OD = 25%, 45%, and 65%) were explored to modify PADM, while glutaraldehyde (GA), dehydrathermal treatment (DHT), and carbodiimide (EDC) were used as the control. The efficacy of ADA on modifying PADM increased along with the rising of oxidation degree. The ADA (OD = 65% and 45%) groups showed better mechanical and thermal stability, crosslink density, and resistance to enzymatic degradation than ADA (OD = 25%) and DHT + EDC group. Meanwhile, the structure of PADM crosslinked by ADA (OD = 45% and 65%) were maintained largely. Further, ADA (OD = 45%) group revealed better cytocompatibility than DHT + EDC, ADA (OD = 65%) and GA group. Considering the balance of cytocompatibility and physicochemical behavior, ADA (OD = 45%) was more suitable as a natural derived crosslinker to modify PADM in tissue engineering. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43550. [ABSTRACT FROM AUTHOR]

The advantages of bioceramics, such as biocompatibility and osteoconduction, have been widely used for bone repair and substitute as bone tissue-engineering materials. Bioceramic scaffolds however still need improvement to meet the requirements for complex bone repair. The aim of this study was to develop novel bioscaffolds for bone regeneration, based on the combination of silk fibroin (SF) and calcium polyphosphate (CPP) composite scaffolds. In this study, Bombyx mori silk fibroin (BMSF) and Antheraea pernyi silk fibroin (APSF) were prepared, and applied into CPP scaffolds with glutaraldehyde crosslinking to form the BMSF/CPP and APSF/CPP bioceramics. These scaffolds were then undergone the strength tests, morphology evaluation, and assessments for biodegradation and biocompatibility. Our results showed that the CPP-type bioceramics presented a higher compressive strength and enhanced degradation after the silk fibroin was doped into a CPP structure. Moreover, the BMSF/CPP and APSF/CPP-type scaffolds exhibited lower cellular toxicity than those of the CPP and HA types. Considering the improved mechanical characteristics and degradation as well as ready availability, SF/CPP may be considered a suitable bioceramic for bone tissue-engineering. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this work was to prepare chitosan/silk fibroin (CS/SF) blending membranes crosslinked with alginate dialdehyde (ADA) as wound dressings and to evaluate the physical properties and biocompatibility of the membranes. The morphology of membrane was observed by scanning electron microscopy (SEM) which showed that the well consistency of these two compositions. Further, the stability, water absorption and water vapor permeability of the ADA fixed CS/SF membranes could meet the needs of wound dressing. Furthermore, the biocompatibility of ADA fixed membranes was investigated by MTT assays and SEM in vitro, and the membranes were found to promote the cell attachment and proliferation. These results suggest that ADA fixed CS/SF blending membranes with a suitable ratio could be a promising candidate for wound healing applications. [Copyright &y& Elsevier]

Abstract: In this study, porcine aortic tissues were fixed with genipin to construct an esophageal prosthesis. In vitro characterization was performed and in vivo biocompatibility experiments were undertaken to evaluate the biological properties of genipin-fixed porcine aortic tissues. The porcine aortic tissues fixed with genipin at pH 4.0, 0.625g/100ml initial fixative concentrations for 7days showed more favorable characteristics. It was characterized by low antigenicity, good epithelial cellular compatibility, favorable biomechanical properties for an esophageal prosthesis, high resistance against enzymatic degradation and be readily available. The porcine aortic tissues fixed with genipin also showed good biocompatibility in vivo. The present study demonstrated that the genipin-fixed porcine aortic tissues could be a promising material for the construction of an esophageal prosthesis or fabricating scaffold for a tissue engineered esophagus. [Copyright &y& Elsevier]

Despite its crucial role in directing cell fate in healthy and diseased tissues, improvements in physical-chemical properties and biocompatibility of type-I collagen are still needed. In this report, we described combined and facile method to modify collagen. The collagen film was first modified by procyanidins solution, in which, then subjected to further crosslinked by dialdehyde alginate, resulting in collagen-procyanidins-dialdehyde alginate film. The properties of the crosslinked collagen films were investigated and the results were discussed. Results from differential scanning calorimetry and thermo gravimetric analysis suggested that the thermal stabilities of the collagen-procyanidins-dialdehyde alginate film were significantly improved. The mechanical properties of collagen-procyanidins-dialdehyde alginate film in terms of elongation at break and tensile strength increased approximately 2-fold and 3-fold, respectively compare to pure collagen film. In addition, the resistance to collagenase degradation of collagen-procyanidins-dialdehyde alginate film was remarkably promoted. The results from methyltetrazolium assay and confocal laser scanning microscopy showed that no cytotoxicity of collagen film was introduced by the combined crosslinking method. Thus, the novel combined by procyanidins-dialdehyde alginate crosslinking method shown in this study provided a non-toxic and efficient crosslinking method that improved various properties of collagen film, which has great potential applications in biomedical materials. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to scale-up the usage of strontium-doped calcium polyphosphate (SCPP) to major load-bearing applications in bone substitute application. SCPP powders were used to prepare biological coatings on titanium (Ti) substrates by plasma-spraying under a series of different conditions. Microstructure and bonding strength (with titanium substrates) of the SCPP coatings were investigated by an inductively coupled plasma-mass spectrometer, X-ray diffraction analysis, a scanning electron microscope and a strength test machine. The results showed the main crystal type of coating remained β-crystal SCPP. The surface and cross-sectional morphologies of coatings showed that the SCPP coatings were fairly dense. The bonding strength between the SCPP and Ti was higher than normal plasma spraying coatings. Furthermore, the research on the interactions between ROS17/2.5 cells and various SCPP coatings-Ti substrates indicated that the coating-implants possessed good cytocompatibility with osteoblasts. Therefore, SCPP is considered to be a biological coating material with good prospect in clinical application. [Copyright &y& Elsevier]

The development of hydrogels for bone regeneration has highlighted the challenge that load-bearing hydrogels need to be biocompatible while achieving high strength. Several approaches have been reported to improve the toughness of hydrogels, but achieving high toughness and biocompatibility simultaneously remains a challenge. Here we report a polyacrylic acid/alginate/demineralized bone matrix (PAA/Alg/DBM) hybrid double network hydrogel, which was synthesized by a two-step sequential polymerization with embedded DBM, possessing both high strength and biocompatibility. With the persistence of DBM, it can promote the synthesis of VEGF and bFGF and the ALP activity of MG63 cells on hydrogel. All the results suggest that this hybrid double network hydrogel have potential for future application in bone regeneration. [ABSTRACT FROM AUTHOR]

Abstract: Biological tissues must be chemically fixed before they can be implanted in humans, due to the immediate degradation and presence of antigenicity of naturally derived tissues. To provide a crosslinking reagent which is cytocompatible and may prepare biocompatible fixed tissues, a novel crosslinking agent, alginate dialdehyde (ADA), was employed to fix biological tissues by our group. The study was to evaluate the cytocompatibility of ADA for biological tissue fixation. Glutaraldehyde and genipin counterparts were used as controls. The result suggested that the cytotoxicity of ADA was significantly lower than that of glutaraldehyde and genipin. Additionally, in the evaluation of cytotoxicity of fixed tissue itself and the residues, as well as the cell adhesion property, ADA-fixed tissue was significantly superior to its glutaraldehyde counterpart and comparable to its genipin counterpart. The results obtained in this study demonstrate that ADA is a cytocompatible crosslinking reagent for biological tissue fixation. [Copyright &y& Elsevier]