Long-term observation of polycaprolactone small-diameter vascular grafts with thickened outer layer and heparinized inner layer in rabbit carotid arteries.

In our previous study, the pristine bilayer small-diameterin situtissue engineered vascular grafts (pTEVGs) were electrospun from a heparinized polycaprolactone (PCL45k) as an inner layer and a non-heparinized PCL80k as an outer layer in the thickness of about 131 µm and 202 µm, respectively. However, the hydrophilic enhancement of inner layer stemmed from the heparinization accelerated the degradation of grafts leading to the early formation of arterial aneurysms in a period of 3 months, severely hindering the perennial observation of the neo-tissue regeneration, host cell infiltration and graft remodeling in those implanted pTEVGs. Herein to address this drawback, the thickness of the outer layers was increased with PCL80k to around 268 µm, while the inner layer remained unchangeable. The thickened TEVGs named as tTEVGs were evaluated in six rabbits via a carotid artery interpositional model for a period of 9 months. All the animals kept alive and the grafts remained patent until explantation except for one whose one side of arterial blood vessels was occluded after an aneurysm occurred at 6 months. Although a significant degradation was observed in the implanted grafts at 9 month, the occurrence of aneurysms was obviously delayed compared to pTEVGs. The tissue stainings indicated that the endothelial cell remodeling was substantially completed by 3 months, while the regeneration of elastin and collagen remained smaller and unevenly distributed in comparison to autologous vessels. Additionally, the proliferation of macrophages and smooth muscle cells reached the maximum by 3 months. These tTEVGs possessing a heparinized inner layer and a thickened outer layer exhibited good patency and significantly delayed onset time of aneurysms.

Study on the Effect of Type III Recombinant Humanized Collagen on Human Vascular Endothelial Cells.

The effect and mechanism of type III recombinant humanized collagen (hCOLIII) on human vascular endothelial EA.hy926 cells at the cellular and molecular levels were investigated. The impact of hCOLIII on the proliferation of EA.hy926 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid assay, the effect of hCOLIII on cell migration was investigated by scratch assay, the impact of hCOLIII on cell cycle and apoptosis was detected by flow cytometry, the ability of hCOLIII to induce angiogenesis of EA.hy926 cells was evaluated by angiogenesis assay, and the effect of hCOLIII on vascular endothelial growth factor (VEGF) expression was detected by real-time reverse transcription-polymerase chain reaction analysis. The hCOLIII at concentrations of 0.5, 0.25, and 0.125 mg/mL all showed specific effects on the proliferation and migration of human vascular endothelial cells. It could also affect the cell cycle, increase the proliferation index, and increase the expression level of VEGF in human vascular endothelial cells. In the meantime, hCOLIII at the concentration of 0.5 mg/mL also showed a promoting effect on vessel formation. hCOLIII can potentially promote the endothelization process of blood vessels, mainly by affecting the proliferation, migration, and vascular-like structure of human endothelial cells. At the same time, hCOLIII can promote the expression of VEGF. This collagen demonstrated its potential as a raw material for cardiovascular implants.

Selective Photoelectrochemical Oxidation of Glycerol to Glyceric Acid on (002) Facets Exposed WO3 Nanosheets.

Glycerol is a byproduct of biodiesel production. Selective photoelectrochemical oxidation of glycerol to high value-added chemicals offers an economical and sustainable approach to transform renewable feedstock as well as store green energy at the same time. In this work, we synthesized monoclinic WO3 nanosheets with exposed (002) facets, which could selectively oxidize glycerol to glyceric acid (GLYA) with a photocurrent density of 1.7 mA cm-2 , a 73 % GLYA selectivity and a 39 % GLYA Faradaic efficiency at 0.9 V vs. reversible hydrogen electrode (RHE) under AM 1.5G illumination (100 mW cm-2 ). Compared to (200) facets exposed WO3 , a combination of experiments and theoretical calculations indicates that the superior performance of selective glycerol oxidation mainly originates from the better charge separation and prolonged carrier lifetime resulted from the plenty of surface trapping states, lower energy barrier of the glycerol-to-GLYA reaction pathway, more abundant active sites and stronger oxidative ability of photogenerated holes on the (002) facets exposed WO3 . Our findings show great potential to significantly contribute to the sustainable and environmentally friendly chemical processes via designing high performance photoelectrochemical cell via facet engineering for renewable feedstock transformation.

Molecular Heptazine-Triazine Junction over Carbon Nitride Frameworks for Artificial Photosynthesis of Hydrogen Peroxide.

Revealing the photocatalytic mechanism between various junctions and catalytic activities has become a hotspot in photocatalytic systems. Herein, an internal molecular heptazine/triazine (H/T) junction in crystalline carbon nitride (HTCN) is constructed and devoted to selective two-electron oxygen reduction reaction (2e- ORR) for efficient hydrogen peroxide (H2 O2 ) production. In-situ X-ray diffraction spectra under various temperatures authenticate the successful formation of molecular H/T junction in HTCN during the calcining process rather than physically mixing. The increased surface photovoltage and transient photovoltage signals, and the decreased exciton binding energy undoubtably elucidate that an obvious increasement of carrier density and diffusion capability of photogenerated electrons are realized over HTCN. Additionally, the analyses of in situ photoirradiated Kelvin probe force microscopy and femto-second transient absorption spectra reveal the successful construction of the strong internal built-in-electric field and the existence of the majority of long-lived shallow trapped electrons associated with molecular H/T junction over HTCN, respectively. Benefiting from these, the photocatalytic results exhibit an incredible improvement (96.5-fold) for H2 O2 production. This novel work provides a comprehensive understanding of the long-lived reactive charges in molecular H/T junctions for strengthening the driving-force for photocatalytic H2 O2 production, which opens potential applications for enhancing PCN-based photocatalytic redox reactions.

Construction of a specialized integrated simulation platform for molecule screening based on scientific computing workflow engine.

Numerical simulation is an efficient tool for evaluation and prediction of material properties and behavior in many industrial domains such as the development of novel materials and medicines. For numerical studies of complex processes or systems with high fidelity, various data processing tools, modeling and simulation programs are typically involved, desiring an integrated platform that can effectively manage the collaboration of such software resources and the execution of the underlying simulation workflow for efficiency purpose. Such a platform could be practically built with a scientific computing workflow engine that focuses on the automatic scheduling and execution of a batch of interrelated computing tasks. In this work, the main procedures on construction of a specialized integrated simulation platform for material research based on a general purpose scientific computing workflow engine named HSWAP is introduced in detail, and its application to molecule screening process of energetic materials is demonstrated. Due to the flexibility and the extensibility of the platform, the work could be handily extended to the screening of other materials such as protein to find optimized protein structures or high entropy alloys to find the best configuration of component contents, as well as other application scenarios such as geometry optimizations of complex structures.

Research progress of implantation materials and its biological evaluation.

With the development of modern material science, life science and medical science, implantation materials are widely employed in clinical fields. In recent years, these materials have also evolved from inert supports or functional substitutes to bioactive materials able to trigger or promote the regenerative potential of tissues. Reasonable biological evaluation of implantation materials is the premise to make sure their safe application in clinical practice. With the continual development of implantation materials and the emergence of new implantation materials, new challenges to biological evaluation have been presented. In this paper, the research progress of implantation materials, the progress of biological evaluation methods, and also the characteristics of biocompatibility evaluation for novel implantation materials, like animal-derived implantation materials, nerve contact implantation materials, nanomaterials and tissue-engineered medical products were reviewed in order to provide references for the rational biological evaluation of implantable materials.

Fabrication and performance evaluation of PLCL-hCOLIII small-diameter vascular grafts crosslinked with procyanidins.

Cardiovascular disease has become one of the main causes of death. It is the common goal of researchers worldwide to develop small-diameter vascular grafts to meet clinical needs. Collagen is a valuable biomaterial that has been used in the preparation of vascular grafts and has shown good results. Recombinant humanized collagen (RHC) has the advantages of clear chemical structure, batch stability, no virus hazard and low immunogenicity compared with animal-derived collagen, which can be developed as vascular materials. In this study, Poly (l-lactide- ε-caprolactone) with l-lactide/ε-caprolactone (PLCL) and type III recombinant humanized collagen (hCOLIII) were selected as raw materials to prepare vascular grafts, which were prepared by the same-nozzle electrospinning apparatus. Meanwhile, procyanidin (PC), a plant polyphenol, was used to cross-link the vascular grafts. The physicochemical properties and biocompatibility of the fabricated vascular grafts were investigated by comparing with glutaraldehyde (GA) crosslinked vascular grafts and pure PLCL grafts. Finally, the performance of PC cross-linked PLCL-hCOLIII vascular grafts were evaluated by rabbit carotid artery transplantation model. The results indicate that the artificial vascular grafts have good cell compatibility, blood compatibility, and anti-calcification performance, and can remain unobstructed after 30 days carotid artery transplantation in rabbits. The grafts also showed inhibitory effects on the proliferation of SMCs and intimal hyperplasia, demonstrating its excellent performance as small diameter vascular grafts.

Hydrogel-complexed small-diameter vascular graft loaded with tissue-specific vascular extracellular matrix components used for tissue engineering.

Tissue engineering is thought to the most promising strategy to develop successful small diameter vascular grafts (SDVG) to meet clinical demand. The introduction of natural substances into the SDVG made from synthetic biomaterials can improve the biocompatibility to promote the regeneration of SDVG in vivo. Due to that natural materials from different sources may have property deviation, it is vital to determine the source of natural materials to optimize SDVG fabrication for tissue engineering applications. In this study, bioactive SDVGs were prepared via coating of heparin-modified poly-(ε-caprolactone) scaffolds with a precursor solution containing vascular extracellular matrix (VECM) components and subsequent in situ gelation. The mechanical properties, degradation behaviors, and morphologies of the SDVGs were thoroughly characterized and evaluated. Cell experiments demonstrated the in vitro tissue specificity of the VECM that could promote the proliferation of endothelial cells better than skin-derived collagen. Furthermore, three types of SDVGs, SDVGs with blank hydrogel, SDVGs with skin-derived collagen, and SDVGs with vascular extracellular matrix (VECM-SDVGs), were implanted into the abdominal aorta of rats for one month. The explanted SDVGs were then comprehensively evaluated using hematoxylin and eosin, Masson, von Kossa staining, and immunohistochemical staining for CD31, α-SMA, and MHC. The results showed that the VECM-SDVGs showed the best endothelium regeneration, appropriate intima regeneration, and no calcification, indicating the in vivo specificity of the fabricated VECM-SDVGs. Thus, long-term implantation of VECM-SDVGs was performed. The results showed that a complete endothelial layer formed after 6 months of implantation, and the amount of contractile SMCs in the regenerative smooth muscle layer approached the amount of native aorta at the 12th month. Consequently, relying on vascular tissue specificity, VECM-SDVGs can modulate the regenerative behavior of the implanted SDVGs in vivo to achieve satisfactory vascular regeneration both in short- and long-term implantation.

Hydrogel Dressing Containing Basic Fibroblast Growth Factor Accelerating Chronic Wound Healing in Aged Mouse Model.

Due to the decreasing self-repairing ability, elder people are easier to form chronic wounds and suffer from slow and difficult wound healing. It is desirable to develop a novel wound dressing that can accelerate chronic wound healing in elderly subjects to decrease the pain of patients and save medical resources. In this work, Heparin and basic fibroblast growth factor(bFGF) were dissolved in the mixing solution of 4-arm acrylated polyethylene glycol and dithiothreitol to form hydrogel dressing in vitro at room temperature without any catalysts, which is convenient and easy to handle in clinic application. In vitro re-lease test shows the bFGF could be continuously released for at least 7 days, whereas the dressing surface integrity maintained for 3 days degradation in PBS solution. Three groups of treatments including bFGF-Gel, bFGF-Sol and control without any treatment were applied on the full-thickness wound on the 22 months old mice back. The wound closure rate and histological and immunohistochemical staining all illustrated that bFGF-Gel displayed a better wound healing effect than the other two groups. Thus, as-prepared hydrogel dressing seems supe-rior to current clinical treatment and more effective in elderly subjects, which shows promising potential to be applied in the clinic.

Fabrication of heparinized small diameter TPU/PCL bi-layered artificial blood vessels and in vivo assessment in a rabbit carotid artery replacement model.

Increasingly growing problems in vascular access for long-term hemodialysis lead to a considerable demand for synthetic small diameter vascular prostheses, which usually suffer from some drawbacks and are associated to high failure rates. Incorporating the concept of in situ tissue engineering (TE) into synthetic small diameter blood vessels, for example, thermoplastic poly(ether urethane) (TPU) ones, could provide an alternative approach for vascular access that profits from the advantages of excellent mechanical properties of synthetic polymer materials (early cannulation) and unique biointegration regeneration of autologous neovascular tissues (long-term fistulae). In this study, a kind of heparinized small diameter (d = 2.5 mm) TPU/poly(ε-caprolactone) (TPU/PCL-Hep) bi-layered blood vessels was electrospun with an inner layer of PCL and an outer layer of TPU. Afterward, the inner surface heparinization was conducted by coupling H2N-PEG-NH2 to the corroded PCL layer and then heparin to the attached H2N-PEG-NH2 via the EDCI/NHS chemistry. Herein a heparinized PCL inner layer could not only inhibit thrombosis, but also provide sufficient space for the neotissue regeneration via biodegradation with time. Meanwhile, a TPU outer layer could confer the vascular access the good mechanical properties, such as flexibility, viability and fitness of elasticity between the grafts and host blood vessels as evidenced by the adequate mechanical properties, such as compliance (4.43 ± 0.07%/ 100 mmHg), burst pressure (1447 ± 127 mmHg) and suture retention strength (1.26 ± 0.07 N) without blood seepage after implantation. Furthermore, a rabbit carotid aortic replacement model for 5 months was demonstrated 100% animal survival and 86% graft patency. Puncture assay also revealed the puncture resistance and self-sealing (hemostatic time < 2 min). Histological analysis highlighted neotissue regeneration, host cell infiltration and graft remodeling in terms of extracellular matrix turnover. Altogether, these results showed promising aspects of small diameter TPU/PCL-Hep bi-layered grafts for hemodialytic vascular access applications.

The crescendo pulse frequency of shear stress stimulates the endothelialization of bone marrow mesenchymal stem cells on the luminal surface of decellularized scaffold in the bioreactor.

A completely confluent endothelial cell (EC) monolayer is required to maintain proper vascular function in small diameter tissue-engineered vascular graft (TEVG). However, the most effective method for EC attachment to the luminal surface and formation of an entire endothelium layer that works in vitro remains a complicated challenge that requires urgent resolution. Although pulsatile flow has been shown to be better suited for the generation of functional endothelium, the optimal frequency setting is unknown. Several pulsatile flow frequencies were used to implant rat bone mesenchymal stem cells (MSC) into the lumen of decellularized porcine carotid arteries. The endothelium's integrity and cell activity were investigated in order to determine the best pulse frequency settings. The results showed that MSC were maximally preserved and exhibited maximal morphological changes with improved endothelialization performance in response to increased pulse stimulation frequency. Increased pulse frequency stimulation stimulates the expression of mechanoreceptor markers, cytoskeleton reorganization in the direction of blood flow, denser skeletal proteins fibronectin, and stronger intercellular connections when compared to constant pulse frequency stimulation. MSC eventually develops an intact endothelial layer with anti-thrombotic properties on the inner wall of the decellularized tubular lumen. Conclusion: The decellularized vessels retain the three-dimensional structure of the vasculature, have a surface topography suitable for MSC growth, and have good mechanical properties. By increasing the frequency of pulsed stimulation, MSC endothelialize the lumen of the decellularized vasculature. It is expected to have anti-thrombotic and anti-neointimal hyperplasia properties after implantation, ultimately improving the patency of TEVG.

Homogeneous Carbon/Potassium-Incorporation Strategy for Synthesizing Red Polymeric Carbon Nitride Capable of Near-Infrared Photocatalytic H2 Production.

The efficient utilization of near-infrared (NIR) light for photocatalytic hydrogen generation is vitally important to both solar hydrogen energy and hydrogen medicine, but remains a challenge at present, owing to the strict requirement of the semiconductor for high NIR responsiveness, narrow bandgap, and suitable redox potentials. Here, an NIR-active carbon/potassium-doped red polymeric carbon nitride (RPCN) is achieved for by using a similar-structure dopant as the melamine (C3 H6 N6 ) precursor with the solid KCl. The homogeneous and high incorporation of carbon and potassium remarkably narrows the bandgap of carbon nitride (1.7 eV) and endows RPCN with a high NIR-photocatalytic activity for H2 evolution from water at the rate of 140 µmol h-1 g-1 under NIR irradiation (700 nm ≤ λ ≤ 780 nm), and the apparent quantum efficiency is high as 0.84% at 700 ± 10 nm (and 13% at 500 ± 10 nm). A proof-of-concept experiment on a tumor-bearing mouse model verifies RPCN as being capable of intratumoral NIR-photocatalytic hydrogen generation and simultaneous glutathione deprivation for safe and high-efficacy drug-free cancer therapy. The results shed light on designing efficient photocatalysts to capture the full spectrum of solar energy, and also pioneer a new pathway to develop NIR photocatalysts for hydrogen therapy of major diseases.

Water-Stable Zero-Dimensional (C4H9)4NCuCl2 Single Crystal with Highly Efficient Broadband Green Emission.

Here, we report (C4H9)4NCuCl2 single crystals with a luminous intensity that remains largely the same after soaking in water for 24 h. (CH9)4NCuCl2 has a new type zero-dimensional framework, in which the isolated [CuCl2]- anions are wrapped by organic (C4H9)4N+ cations. As expected, (C4H9)4NCuCl2 shows a broad emission band at 508 nm with a photoluminescence quantum yield of approximately 82% at room temperature, stemming from self-trapped exciton (STE) emission. Temperature-dependent photoluminescence measurement reveals that there is an energy barrier ΔE (24.0 meV) between the intrinsic state and STE state, which leads to the increase in emission intensity with an increase in temperature (98-278 K), while the emission intensity begins to decrease when the temperature is higher than 278 K due to the effects of both thermal quenching and carrier scattering. Our findings provide a new idea for the design of lead-free anti-water stability metal halide materials.

Bulk assembly of a 0D organic tin(ii)chloride hybrid with high anti-water stability.

A lead-free compound, (TBAC)SnCl3 (TBAC = tetrabutylammonium chloride), with high anti-water stability was reported, which can be stable in water for 24 hours. Upon photoexcitation, this compound exhibits a green photoluminescence (PL) centered at 523 nm with a larger Stokes shift of 260 nm at room temperature (RT), stemming from self-trapped exciton (STE) emission.

Gelatin coating promotes in situ endothelialization of electrospun polycaprolactone vascular grafts.

Rapid endothelialization is crucial for in situ tissue engineering vascular grafts to prevent graft failure in the long-term. Gelatin is a promising nature material that can promote endothelial cells (ECs) adhesion, proliferation, and migration. In this study, the internal surface of electrospun polycaprolactone (PCL) vascular grafts was coated with gelatin. Endothelialization and vascular wall remolding were investigated by imaging and histological studies in the rat abdominal aorta replacement model. The endothelialization of heparinized gelatin-coated PCL (GP-H) vascular grafts was more rapid and complete than heparinized PCL (P-H) grafts. Intimal hyperplasia was milder in the GP-H vascular grafts than the P-H vascular grafts in the long-term. Meanwhile, smooth muscle cells (SMCs) and extracellular matrix (ECM) regeneration were better in the GP-H vascular grafts. By comparison, an aneurysm was observed in the P-H group in 6 months. Calcification was observed in both groups. All vascular grafts were patient after implantation in both groups. Our results showed that gelatin coating on the internal surface of PCL grafts is a simple and effective way to promote endothelialization. A more rapid endothelialization and complete endothelium can inhibit intimal hyperplasia in the long-term.

Porcine carotid arteries decellularized with a suitable concentration combination of Triton X-100 and sodium dodecyl sulfate for tissue engineering vascular grafts.

Tissue engineering vascular grafts (TEVGs) constructed by decellularized arteries have the potential to replace autologous blood vessels in bypass surgery for patients with cardiovascular disease. There are various methods of decellularization without a standard protocol. Detergents approaches are simple, and easy control of experimental conditions. Non-ionic detergent Triton X-100 and ionic detergent sodium dodecyl sulfate (SDS) are the most commonly used detergents. In this study, we used Triton X-100 and SDS with different concentrations to decellularize porcine carotid arteries. After that, we investigated the acellular effect and mechanical properties of decellularized arteries to find a promising concentration combination for decellularization. Results showed that any detergents' combination would damage the inherent structure of extracellular matrix, and the destruction increased with the increase of detergents' concentration. We concluded that the decellularization approach of 0.5% Triton X-100 for 24 h combined with 0.25% SDS for 72 h could help to obtain decellularized arteries with minimum destruction. This protocol may be able to prepare a clinically suitable vascular scaffold for TEVGs.

Preparation recombination human-like collagen/fibroin scaffold and promoting the cell compatibility with osteoblasts.

On this basis, a novel recombinant human-like collagen (RHLC)/silk fibroin scaffold material with high porosity and controllable aperture was prepared. The compatibility of osteoblasts (OB) with the blends was tested in vitro. The morphology, adhesion and growth of scaffold cells were observed by scanning electron microscope and laser confocal microscope. Extensive measurements, including 3-[4, 5-dimethylthiazole-2-acyl]-2, 5-diphenyl tetrabrominate assays, intracellular total protein content, and alkaline phosphatase activity assays were performed after 7 days of culture. Survival and protein content increased in RHLC/fibroin stents. LSCM and SEM results confirmed that the cells grew better in the mixed scaffolds than in the pure silk scaffolds, and showed that the cells were easy to adhere and diffuse in the RHLC/silk scaffolds. RHLC/silk fibroin scaffolds are promising biomaterials for bone tissue engineering.

Characterization of a heparinized decellularized scaffold and its effects on mechanical and structural properties.

Decellularization is a promising approach in tissue engineering to generate small-diameter blood vessels. However, some challenges still exist. We performed two decellularization phases to develop an optimal decellularized scaffold and analyze the relationship between the extracellular matrix (ECM) composition and mechanical properties. In decellularization phase I, we tested sodium dodecylsulfate (SDS), Triton X-100 (TX100) and trypsin at different concentrations and exposure times. In decellularization phase II, we systematically compared five combined decellularization protocols based on the results of phase I to identify the optimal method. These protocols tested cell removal, ECM preservation, mechanical properties, and residual cytotoxicity. We further immobilized heparin to optimal decellularized scaffolds and determined its anticoagulant activity and mechanical properties. The combined decellularization protocol comprising treatment with 0.5% SDS followed by 1% TX100 could completely remove the cellular contents and preserve the mechanical properties and ECM architecture better. In addition, the heparinized decellularized scaffolds not only had sustained anticoagulant activity, but also similar mechanical properties to native vessels. In conclusion, heparinized decellularized scaffolds represent a promising direction for small-diameter vascular grafts, although further in vivo studies are needed.

Controlled preparation of lignin/titanium dioxide hybrid composite particles with excellent UV aging resistance and its high value application.

In this work, a novel lignin/titanium dioxide (QAL/TiO2) hybrid composite with regular microstructure and synergistically enhanced UV absorption properties was synthesized by a simple hydrothermal method using lignin and butyl titanate. The prepared QAL/TiO2 composite is hybrid structure in which lignin and TiO2 is uniformly embedded, and has strong chemical bond bonding force. The QAL/TiO2 hybrid composite particles were used for doping modification of waterborne polyurethane (WPU), which had good interfacial compatibility and dispersibility in WPU. The obtained WPU + QAL/TiO2 film shows excellent UV shielding performance and great mechanical properties, the tensile strength and elongation at break are significantly improved compared with pure WPU film. And it also has excellent anti-UV aging property, that the mechanical performance basically remains unchanged after 96 h of high power ultraviolet irradiation. This work not only provides a kind of lignin/TiO2 hybrid composite with neat structure, good dispersion and excellent optical properties, but also has great significance for the high-valued utilization of biomass resources.