Effects of Coupled-/soluble-Copper, Generating from Copper-doped Titanium Dioxide Nanotubes on Cell Response.

BACKGROUND: Endothelialization in vitro is a very common method for surface modification of cardiovascular materials. However, mature endothelial cells are not suitable because of the difficulty in obtaining and immunogenicity. METHODS: In this patent work, we determined the appropriate amount of copper by constructing a copper- loaded titanium dioxide nanotube array that can catalyze the release of nitric oxide, compared the effects of coupled-/soluble-copper on stem cells, and then induced stem cells to differentiate into endothelial cells. RESULTS: The results showed that it had a strong promotion effect on the differentiation of stem cells into endothelial cells, which might be used for endothelialization in vitro. CONCLUSION: SEM and EDS results prove that a high content of copper ions are indeed doped onto the surface of nanotubes with small amounts of Cu release. The release of NO confirms that the release of several samples within a period of time is within the physiological concentration.

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.

The self-organized differentiation from MSCs into SMCs with manipulated micro/Nano two-scale arrays on TiO2 surfaces for biomimetic construction of vascular endothelial substratum.

The endothelialization on biomaterial surface has been seen as an important strategy to solve the clinic problems with the cardiovascular implant device. However, the continuous and large surfaces such as artificial heart or artificial cardiac valve cannot maintain the structural and functional stability of the endothelium without the supply of substratum structures. Herein, we combined the micro/nano technology of material surface engineering and the tissue engineering technology to construct the biomimetic vascular endothelial substratum for high quality and complete endothelialization through inducing self-organized differentiation from MSCs to SMCs, controlling their self-aggregation structure and further manipulating micro-tissue on the surface. In the present work, the micro/nano two-scale features of surface were manipulated by preparing the micro arrays of TiO2 nanotubes on titanium surface. The responses of MSCs to these surfaces revealed that the MSCs could be highly regulated and then their self-organized differentiation to SMCs could be induced and improved based on anchoring of the adhesion complex protein and traction of F-actin adjusted by the micro/nano features of the surfaces. Besides, SMCs' self-aggregation structure could also be adjusted effectively by manipulating micro/nano features on two-scale surfaces, and three types of tissue-like structures could be achieved for the further use in formation and surface manipulation of micro-tissue and biomimetic construction of vascular endothelial substratum.

The co-deposition coating of collagen IV and laminin on hyaluronic acid pattern for better biocompatibility on cardiovascular biomaterials.

Construct a coating to repair the endothelium function is the ordinary and effective method to get out of the troubles which introduced by the cardiovascular implant devices. It indeed has plenty works on function construction which could inhibit the hyperplasia or accelerate the endothelialization with different functional proteins or molecules. However, a complete and healthy endothelium couldn't survive without the environment around. Thus, a logical biomimetic reconstruction with structure and function factors which using hyaluronic acid patterns to imitate the blood flow shear stress and co-depositing collagen type IV and laminin to achieve the biofunction of basement membrane had been proposed and realized in this work. After the tests of hemocompatibility, cytocompatibility and tissue compatibility, it had been indicated that this biomimetic coating could inhibit the adhesion of platelets, promote the proliferation and biofunction of endothelium cells, regulate smooth muscle cells with contractile phenotype and have much lower inflammatory response which might be a meaningful strategy on reconstruction and repairing of endothelium.