The Biomimetic Construction Of Vascular Endothelial Substratum And Research On Engineering Stem Cells Regulation

The endothelialization on biomaterial surface has been seen as an important strategy to solve the clinic problems with the cardiovascular implant device.However,the endothelialization with high quality and completely repairing on the continuous and large surfaces still cannot be solved because of the limited cell migration and unable to grow in.On the one hand,the vascular substratum in the microenvironment around vascular endothelium contains healthy oriented SMCs layer and extracellular matrix which plays important roles in structural and functional stability of the endothelium.On the other hand,designing and regulating the cell microenvironment,can manipulate the behaviors of cells,especially the stem cells,which can induce the self-organized differentiation and micro tissue forming.Therefore,the biomimetic construction of vascular endothelial substratum has been proposed as a strategy of reconstruction to maintain the stability of endothelium structure and function.Meanwhile,the key cues of engineering stem cells regulation have been analyzed and the construction of artificial extracellular matrix on stem cell surfaces to regulate the stem cell microenvironment also has been proposed as a new strategy for stem cell applications.In this paper,the biomimetic structure which have excellent blood compatibility in early stage and endothelialization with high quality and completely repairing in a long term has been constructed.The evaluation of MSCs morphology features had been established.Three types of SMCs layer tissue-like structures have been achieved.Two kinds of engineering stem cell construction as “Cell Coating” and “Cell Clothing” for stem cell microenvironment regulation have been proposed.The main content of this paper is as follows:(1)Micro/nano two-scale structures were fabricated on titanium surfaces by photolithography and twice anodic oxidation.The evaluation of cell morphology features had been established.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 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.(2)“Natural” and “biomimetic”,two construction strategies of artificial extracellular matrix for cells embedding had been proposed.The spin coating of Matrigel on polydopamine surface and the co-deposition coating of collagen IV and laminin on hyaluronic acid patterns,which could both reduce clotting and thrombosis,promote the proliferation of ECs and regulate the phenotype of SMCs and MAs.The natural artificial extracellular matrix Matrigel was chosen to construct the biomimetic vascular endothelial substratum.This hybrid construction showed excellent blood compatibility in early stage and endothelialization with high quality and completely repairing in a long term.(3)The key cues of engineering stem cells regulation during the biomimetic construction had been discussed,and the feasibility of engineering construction with artificial extracellular matrix on stem cell surfaces had been analyzed.Set the layer-by-layer assembly construction with hyaluronic acid and collagen as an example,engineering construction of this artificial extracellular matrix on stem cell surfaces to regulate the stem cell microenvironment had been built as “Cell Coating” and “Cell Clothing”,the preliminary research showed that they could promote the adhesion and proliferation and protect from the harmful factors outside.In summary,combined the cardiovascular biomaterials surface modified engineering and engineering stem cell regulation,the biomimetic construction of vascular endothelial substratum and engineering construction with artificial extracellular matrix have been realized which could promote the research on biofunction modified surface,and as an example for stem cell microenvironment designing and regulating,it could also propose a new strategy for stem cell regulation and endothelial repairing on cardiovascular biomaterials surfaces.