Copper and Zinc Co-doped Titanium Dioxide Nanotubes Arrays on Controlling Nitric Oxide Releasing and Regulating the Inflammatory Responses for Cardiovascular Biomaterials.

BACKGROUND: Titanium dioxide (TiO2) nanotubes arrays have shown tremendous application foreground due to their unique characters of structure and performance. However, the single bio-function is still the limit on cardiovascular biomaterials. METHODS: The loadability function provides the possibility for the TiO2 nanotubes arrays to realize composite multifunction. The copper can catalyze the release of nitric oxide to promote the proliferation of endothelium cells and improve the anticoagulant. Also, zinc can adjust the inflammatory responses to improve anti-inflammation. RESULTS: In this patent work, we co-doped the copper and zinc onto TiO2 nanotubes arrays to estimate the hemocompatibility, cytocompatibility and responses of inflammation. The results showed that copper and zinc could introduce better multi-biofunctions to the TiO2 nanotubes arrays for the application in cardiovascular biomaterials. CONCLUSION: In summary, the NTs@Cu/Zn sample as a new composite material in this study had significant biocompatibility in vascular implantation and can be used as a potential material for polymer- free drug-eluting stents.

An Injectable Nanocomposite Hydrogel for Potential Application of Vascularization and Tissue Repair.

In this contribution, an injectable hydrogel was developed with chitosan, gelatin, ß-glycerphosphate and Arg-Gly-Asp (RGD) peptide: this hydrogel is liquid in room temperature and rapidly gels at 37 °C; RGD peptide promises better growth microenvironment for various cells, especially endothelial cells (EC), smooth muscle cells (SMC) and mesenchymal stem cells (MSC). Both stromal cell-derived factor-1 (SDF-1) nanoparticle and vascular endothelial growth factor (VEGF) nanoparticles were loaded in the injectable hydrogel to simulate the natural nanoparticles in the extracellular matrix (ECM) to promote angiogenesis. In vitro EC/SMC and MSC/SMC co-culture experiment indicated that the nanocomposite hydrogel accelerated constructing embryonic form of blood vessels, and chick embryo chorioallantoic membrane model demonstrated its ability of improving cells migration and blood vessel regeneration. We injected this nanocomposite hydrogel into rat myocardial infarction (MI) model and the results indicated that the rats heart function recovered better compared control group. We hope this injectable nanocomposite hydrogel may possess wider application in tissue engineering.

Hydrogen sulphide-releasing aspirin enhances cell capabilities of anti-oxidative lesions and anti-inflammation.

Hydrogen sulphide (H2S) has been considered as a toxic gas for a long time till new researches discovered the endogenous H2S effects on physiological and pathological processes. In virtue of H2S's effects on cellular redox imbalance and aspirin's good anticoagulation property, exogenous H2S donors, such as H2S-releasing aspirin (ACS14), have been explored to attenuate side effects of aspirin on gastrointestinal mucosal damage. However, existing researches mainly focus on the antithrombotic effects. Considering H2S role in angiogenesis and vascular-protection progress, we herein focused on if ACS14 further has the ability to attenuate oxidative lesion and inflammation in human umbilical vein endothelial cells (HUVECs) and macrophages. In this study, we synthesized ACS14 by 5-(4-methoxyphenyl)-1,2-dithiole-3-thione and o-acetylsalicylic acid (aspirin), and the obtained compounds showed the ability to release H2S. Our data illustrated that both aspirin and ACS14 had good cytocompatibility, and could support the proliferation of HUVECs. And, ACS14 was found to be able to promote 1.6 folds increase compared to aspirin. H2S released from ACS14 was detected inside cells, wherein H2S fluorescence intensity increased twofold in 5 µM and 10 µM ACS14 groups than 1 µM group. Owing to reactive oxygen species inside cells being obviously decreased in ACS14 group, the apoptosis rate of HUVEC herein was reduced as low as 1.6% from 60% of blank group. Meanwhile, the tumour necrosis factor alpha release in macrophage was also declined by 15% in ACS14 groups than the others. Basically, the ACS14 we obtained had the cyto-protective and anti-inflammatory capabilities. Potential applications for vascular intima repair in atherosclerosis are further expected.

An injectable scaffold based on temperature-responsive hydrogel and factor-loaded nanoparticles for application in vascularization in tissue engineering.

Controlled release of functional factors contributes to target migration of therapeutic cells and plays a crucial role in the in situ vascularization of tissue repair and regeneration. A biomedical application requires the selective release of multiple factors which will guide the synergy of the cells. Here, we developed an injectable system based on a temperature-responsive hydrogel and stromal cell-derived factor-1 (SDF-1)/vascular endothelial growth factor (VEGF) loaded into two types of nanoparticles to induce migration and rapid proliferation of mesenchymal stem cells (MSCs) and endothelial cells (ECs) via selective SDF-1/VEGF release. Series of in vitro and in vivo experiments demonstrate that our composited system can accurately guide MSCs and ECs for vascularization. In addition, the properties of the nanoparticles and hydrogel, including micro/nanoscales, characteristic of charge, and biocompatibility, played crucial roles for the selective release and cells behavior (target migration and rapid proliferation).

Mechanical Property of TiO2 Nano-Tubes Surface Based on the Investigation of Residual Stress, Tensile Force and Fluid Flow Shear Stress: For Potential Application of Cardiovascular Devices.

The TiO2 nanotube has been anticipated for potential application for cardiovascular implanted devices for its excellent drug loading/release function and biocompatibility. However, its mechanical behavior has rarely been studied as the cardiovascular devices. The tube length is a crucial factor which not only decides the drug loading ability but also influences the devices' mechanical behavior. Therefore, in this work, the TiO2 nanotubes with different tube length (NT2, NT4 and NT6) were fabricated, and their surface energy, residual stress, tensile tolerability and blood flow shear stress tolerability were determined, respectively. The results showed that there were no significant difference for each film samples on surface energy, tensile tolerability and blood flow shear stress tolerability, while NT6 obtained the smallest residual stress. These results indicated that longer TiO2 nanotubes not only meant loading more drugs but also better mechanical properties for surface modification of cardiovascular devices.