用于心血管医疗装置的聚合物材料表面构建与生物相容性评价：聚合物生物材料表面的内皮细胞组织工程化改性

doi:10.3969/j.issn.2095-4344.2016.30.016

中国组织工程研究 ›› 2016, Vol. 20 ›› Issue (30): 4515-4523.doi: 10.3969/j.issn.2095-4344.2016.30.016

• 生物材料综述 biomaterial review • 上一篇下一篇

用于心血管医疗装置的聚合物材料表面构建与生物相容性评价：聚合物生物材料表面的内皮细胞组织工程化改性

陈宝林¹，王东安^2，3

¹呼伦贝尔学院科技处，内蒙古自治区呼伦贝尔市 021008；²浙江大学高分子科学研究所，浙江省杭州市 310027；³ Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA

收稿日期:2016-05-07 出版日期:2016-07-15 发布日期:2016-07-15
通讯作者: 陈宝林，呼伦贝尔学院科技处，内蒙古自治区呼伦贝尔市 021008
作者简介:陈宝林，男，1960年生，河北省新城县人，汉族，1983年东北师范大学毕业，教授，主要从事组织工程材料(生物医用高分子材料)的制备及表征方面的研究。

Surface construction and biocompatibility of polymer materials as cardiovascular devices: modified tissue-engineered endothelial cells on the surface of polymeric biomaterials

Chen Bao-lin¹, Wang Dong-an^{2, 3}

1Bureau of Science & Technology Research, Hulunbuir College, Hulunbuir 021008, Inner Mongolia Autonomous Region, China
2Institute of Polymer Science, Zhejiang University, Hangzhou 310027, Zhejiang Province, China

3Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA

Received:2016-05-07 Online:2016-07-15 Published:2016-07-15
Contact: Chen Bao-lin, Bureau of Science & Technology Research, Hulunbuir College, Hulunbuir 021008, Inner Mongolia Autonomous Region, China
About author:Chen Bao-lin, Professor, Bureau of Science & Technology Research, Hulunbuir College, Hulunbuir 021008, Inner Mongolia Autonomous Region, China

摘要/Abstract

摘要：

文章快速阅读：

背景：用于心血管医疗的生物材料在血液接触性条件下必须具有抗血栓性、对抗生物降解性与抗感染性。
目的：综述用于心血管组织工程的新型植(介)入型聚合物材料(表面)研究进展，从聚合物生物材料表面的内皮细胞组织工程化改性方面考察各种相应改性表面的生物相容性、血液相容性和细胞相容性。
方法：第一作者计算机检索1963至2015年PubMed数据库及万方数据库。英文检索词为“Biocompatibility，Blood compatibility，Biomedical Materials，Biomedical polymer materials”，中文检索词为“生物相容性材料，血液相容性材料，生物医用材料，医用高分子材料”。排除与研究目的相关性差及内容陈旧、重复的文献，保留与生物医用高分子材料的血液相容性研究，进行归纳总结。通过对血管内皮细胞的功能、移植物表面的内皮细胞组织工程化、聚合物生物材料表面促细胞生长因子的固定方法、材料表面内皮化4方面的归纳分析，从聚合物生物材料表面的内皮细胞组织工程化改性方面考察了各种相应改性表面的生物相容性、血液相容性和细胞相容性。
结果与结论：共纳入71篇文献。研制用于心血管组织工程的新型植(介)入型聚合物材料(表面)关键在于对聚合物生物材料表面的内皮细胞组织工程化改性以及对其相应生物相容性与内皮细胞相容性的研究。通过对心血管医疗用聚合物生物材料的种类与应用及其心血管医疗器件和可植入性软组织替代物的深入研究可以发现材料表面与本体的差异则将体现在从表面向本体延伸的很多层分子上，而表面能和分子运动性这2种主要因素决定了其包括本体/表面差异及表面相分离在内的本体/表面行为。如果考虑到对本体-表面的组成差异的理解，则还必须追加另以附加决定因素，即各组分的结晶行为。

ORCID: 0000-0001-8283-783X(Chen Bao-lin)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

关键词: 生物材料, 缓释材料, 材料力学及表面改性, 聚合物材料, 聚合物生物材料, 生物医用聚合物材料

Abstract:

BACKGROUND: As the cardiovascular device, biomaterials applied under the blood-contact conditions should have anti-thrombotic, anti-biodegradable and anti-infective properties.
OBJECTIVE: To review the research progression in polymer materials for implantation and intervention in cardiovascular tissue engineering and to explore the biocompatibility, blood compatibility and cytocompatibility of the surface-modified polymer biomaterials based on the surface endothelialization using tissue engineering techniques.
METHODS: We retrieved PubMed and Wanfang databases for relevant articles publishing from 1963 to 2015. The key words were “Biocompatibility, Blood compatibility, Biomedical Materials, Biomedical polymer materials” in English and Chinese, respectively. Those unrelated, outdated and repetitive papers were excluded. Literatures addressing the blood compatibility, biocompatibility, and cytocompatibility of the surface-modified polymer biomaterials based on the surface endothelialization using tissue engineering techniques were investigated by summarizing function of vascular endothelial cells, tissue-engineered endothelial cells on the implant surface, fixation of cell growth-promoting factor on the surface of polymeric biomaterials, and endothelialization of the material surface.
RESULTS AND CONCLUSION: Totally 71 relevant articles were included. The tissue-engineered modification of endothelial cells on the surface of polymer biomaterials and their biocompatibility and cell compatibility are crucial for developing novel polymer materials for implantation and intervention in cardiovascular tissue engineering. Through in-depth studies of the types and applications of polymer biomaterials, cardiovascular medical devices and implantable soft tissue substitutes, the differences between the surface and the body will be reflected in the many layers of molecules extending from the surface to the body. Two major factors, surface energy and molecular mobility, determine the body/surface behaviors that include body/surface differences and phase separation. Considering the difference between the body/surface composition, an additional determinant is indispensable, that is, the crystallization behavior of each component.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Biocompatible Materials, Tissue Engineering, Endothelial Cells

中图分类号:

R318

陈宝林，王东安. 用于心血管医疗装置的聚合物材料表面构建与生物相容性评价：聚合物生物材料表面的内皮细胞组织工程化改性[J]. 中国组织工程研究, 2016, 20(30): 4515-4523.

Chen Bao-lin, Wang Dong-an. Surface construction and biocompatibility of polymer materials as cardiovascular devices: modified tissue-engineered endothelial cells on the surface of polymeric biomaterials[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(30): 4515-4523.

图/表（结果） 1

Functions of vascular endothelial cells

Cardiovascular disease is initially induced by changes and damage of vascular endothelial cell function. During the detachment of endothelial cells, plasma component (lipid) infiltration, macrophage infiltration and intimal smooth muscle cell proliferation, damage and dysfunction of vascular endothelial cells occur earliest, and play a key role in the occurrence, formation and repair of cardiovascular disease.

Vascular endothelial cells are a cell population as a layer covering the systemic vascular intima. Since this cell population has been successfully cultured in vitro, we have a very in-depth understanding of them. It is now thought that the endothelial layer is not only a barrier to blood and tissue, but also has a variety of other functions, such as reducing vascular permeability, regulating material exchange between tissues and blood, preventing disorderly invasion of plasma components and blood cells, resisting thrombosis, balancing anti-blood coagulation- fibrinolysis system and anti-platelet function, maintaining blood fluidity, adjusting vascular smooth muscle function, synthesizing and secreting factors related to vascular smooth muscle relaxation and contraction, and suppressing migration and proliferation of vascular wall cells^[12-27].

Vascular permeability

In vivo studies have observed that plasma component infiltration to the endothelium appears during endothelial cell division. To understand how lipid traverses endothelial cells, endothelial cells are co-cultured with low density lipoprotein. Results show that ApoB and ApoE receptors of endothelial cells are not associated with transendothelial transport of low density lipoprotein. In contrast, under histamine and thrombin stimulation, the cell permeability is evidently improved, and abundant low density lipoprotein is detected. It is thus clear that some biological factors (e.g., histamine), shear stress and newborn endothelial cells are associated with endothelial cell permeability.

Antithrombotic effects

In the 19^th century, pathologist Virchow proposed three main factors of thrombosis including vascular wall damage, blood stagnation and blood anticoagulant system abnormalities. Under normal circumstances, endothelial cells exert antithrombotic effect and maintain blood fluidity. Nevertheless, with blood vessel wall impairment and the presence of cytokines, tissue factor is activated, antithrombotic ability of endothelial cells weakened, and thrombus easily formed within the blood vessel wall. The mechanisms underlying anti-thrombosis of vascular endothelial cells are as follows: (1) synthesis and secretion of anticoagulant factors, such as thrombomodulin, heparin-like substances and tissue factor pathway inhibitor; (2) synthesis and secretion of pro-fibrinolytic factors, such as tissue plasminogen activator; (3) synthesis and secretion of factors that inhibit angiogenesis and platelet aggregation, such as prostacycline and endothelial-derived relaxing factor. These factors keep the blood circulation and prevent thrombosis.

Proliferation and migration of vascular endothelial cells

Vascular endothelial cells can be induced to exert inhibitory effects on the proliferation of vascular smooth muscle. This mechanism can be affected by various factors secreted from above endothelial cells. Vascular endothelial cells also can proliferate and migrate under the stimulation of platelet, leukocyte-secreted migration factor and flow shear stress. This function is probably associated with arterial repair and neovascularization.

Tissue-engineered endothelial cells on the surface of grafts

Implantation of exogenous endothelial cells

Herring (1978) proposed that endothelial cells implanted on the surface of inhibitors could increase the survival of grafts. Theoretically, the presence of a layer of confluent endothelial cells can elevate the antithrombotic ability of grafts, and prevent the occurrence of pseudointimal hyperplasia. The surface of the intact endothelial cells is negatively charged, which can reject platelet adhesion and exhibit obvious anticoagulant activity. Further studies have discovered that the patency rate of the grafts implanted with endothelial cells and antiplatelet is higher than that of grafts without endothelial cells. Moreover, the grafts implanted with endothelial cells show a strong antibacterial ability. However, these grafts show insignificant differences in lessening pseudointimal hyperplasia in the anastomotic area. In fact, high levels of platelet-derived growth factor (PDGF) can be detected in grafts implanted with endothelial cells, which is associated with the strong effect of PDGF on stimulating the migration and proliferation of smooth muscle cells. Thus, pseudointimal hyperplasia appears.

One of the difficulties in endothelial cell culture is the relatively low density of cells used for transplantation, because of which cells cannot fully attach to grafts. In the process of trying to solve these problems, the researchers attempt to cultivate endothelial cells in two stages. The obtained endothelial cells are amplified in vitro until 100% confluence, and then implanted into the human body. Magometschnigg reported that vascular endothelial cells were implanted on fibrin-coated ePTFE grafts. The early patency rate increased by 20%, and the amputation rate decreased by 20% when above grafts were used in femoral-tibial bypass bridging. The disadvantage of this technique is the possibility of potential infections. Cell culture technology is more difficult and requires a second surgery. Another method to achieve the best cell density is to use microvascular endothelial cells. After small retinal vascular cells obtained by enzyme digestion are implanted on small-diameter Dacron grafts, a confluent endothelial cell layer will form with no thrombosis. As previously reported, a dog model exhibited an elevated 1-year patency rate. The current focus is to implant tissue-engineered endothelial cells on the synthesized grafts. Dichek has successfully transferred plasminogen activator genes into endothelial cells. Thus, modified cells could overexpress this fibrinolytic agent and enhance antithrombotic ability of grafts. In order to stimulate the proliferation and migration of endothelial cells and prevent excessive proliferation of smooth muscle cells, it is possible to make excessive secretion of growth factors and growth inhibitory factors from endothelial cells by transgene^[28-34].

Stimulating re-externalization and angiogenesis of endogenous endothelial cells

A mitogen and chemoattractant for endothelial cells can theoretically stimulate trans-interstitial capillary ingrowth, and enhance endothelialization of synthetic vascular grafts, mainly using fibroblast growth factor (FGF)-1(acidic FGF, aFGF) and FGF-2 (basic FGF, bFGF). Blood vessels can be formed in situ through the re-externalization of endogenous endothelial cells. This process mainly contains migration, proliferation and differentiation of vascular cells. Small blood vessels have been prepared successfully in the body. One of the specific models is: capillary endothelial cells induced by basic fibroblast growth factor project into collagen or fibrin matrix and form blood vessels. Angiogenesis induced by fibroblast growth factor is coupled with proteolytic enzymes produced by endothelial cells. The production of protease is a key step in angiogenesis, and provides a tool for endothelial cells to change extracellular matrix and to enter perivascular spaces. The structure of another vascular model in vivo is: cultured endothelial cells, smooth muscle cells and adventitial fibroblasts are paved in remodeled collagen and Dacron culture systems. Two weeks later, a confluent layer is formed to serve as an endothelial barrier. Different from the human body’s blood vessels, the tissue-engineered blood vessels requires a prosthesis to support and to maintain its structure, and do not contain elastin^{[11, 35-36]}.

Fixation of cell growth-promoting factor on the surface of polymeric biomaterials

To realize the endothelial cellularization on the surface of polymeric biomaterials, bioactive factors should be introduced into the surface of materials. The bioactive factors mainly are proteins. The fixation methods of proteins on the surface of polymers are physical adsorption and chemical fixation. In addition, there are the newly developed ion implantation and self-assembled monolayer methods. Of them, the physical adsorption is relatively convenient, and contains two types: (1) electrostatic adsorption, for example, the heparin containing a negative charge is fixed in a positively charged site of the materials; (2) adsorption by intermolecular force, for example, adsorption between proteins and polymer molecules. In contrast, chemical bonding is more stable and overcomes the shortcoming in physical adsorption, while bioactive molecules cannot exert long-term effects on the surface of the material, and are easy to break away. The chemical fixation usually requires that the substrate surface has hydroxyl group, carboxyl group and amino-group. Therefore, the production of these groups on the surface of the materials by modification is the premise of fixation. Simultaneously, the fixation can cause the degeneration of proteins, and an optimal interaction between cell receptors and proteins cannot be established, so a spacer arm should be inducted in advance on the surface of a polymer. The chemical fixation of proteins usually contains two steps: polymer surface activation and reaction between activated surface and protein^[37-53].

Protein fixation on the surface containing hydroxyl polymer

Sulfonyl chloride method:Hydroxyl group activated by sulfonyl chloride generates reactive sulfonate, and further produces C-N or C-S bond by reaction with protein amine groups or thiol groups so as to fix proteins.

Carbodiimide method: Hydroxyl group activated by imide generates imide-N-methyl ester, which contains leaving group. Thus, urethane bond is produced by reacting with protein aminogen to fix the protein.

Diisocyanate method: Diisocyanate exerts a coupling effect. Hydroxyl group without activation reacts with one end of the coupling agent. One end of the coupling agent reacts to protein and fixes the protein.

Protein fixation on the surface containing arboxyl polymer

The activation of carboxyl group can be carried out by N-hydroxysuccinimide and 1-ethyl-3- (dimethylaminopropyl) carbodiimide.

Protein fixation on the surface containing amino polymers

Amino-group can be coupled to proteins through coupling agents diisocyanate, glycol aldehyde and epoxy resin.

Irradiation fixation

Irradiation fixation refers to fixation of proteins on the surface of polymers by a bifunctional coupling agent under the condition of irradiation. Light activator includes photosensitive azo, benzophenone and acrylate.

Endothelialization of the material surface

Endothelialization of the material surface is a new trend of anticoagulant study. The endothelialized surface mainly refers to pseudo-intimal surface or hybridized surface of endothelial cells and high polymer^[54-56]. Pseudo-intimal surface refers to a layer of stable red thrombosis film forming on their interfaces when the material contacts with blood. The components of the film include plasma protein, platelet, fibrin and leukocytes. Thus, fibroblasts and endothelial cells grow on the film to form an intima similar to blood vessel wall, i.e., the pseudo-intima. At present, artificial blood vessels made of polytetrafluoroethylene with pseudo-intimal surface have been applied in the clinic^[57-58]. It is worth noting that if the pseudo-intima of artificial blood vessels is very thick, nutrition will not support the body, cells will be necrotic and fall off, and coagulation will occur at the exposed part. A large number of studies have been carried out to control the thickness of the pseudo-intima. For example, porous polytetrafluoroethylene invades water-soluble polyvinyl alcohol to form a porous hydrophilic membrane on its surface and to reduce the adsorption of plasma proteins. The pseudo-intima formed on the artificial blood vessel wall is not a true vascular intima. The component and thickness of the formed protein layer cannot be controlled well. Although some improvements have been taken, the pseudo-intima on the artificial blood vessel wall does not achieve an effective compatibility to the transplantation site. Figure 1 shows the artificial blood vessel lined with hybridized endothelial cell polymer^[59]. Endothelialization of material surface is a new trend of anticoagulant research. The blood vessel wall made of human endothelial cells is the only known blood-compatible material. Thus, we make hybridization of endothelial cells and polymers by imitating human blood vessels. That is to culture endothelial cells on the surface of material, finally forming a layer of endothelium. This would be a very ideal way for the improvement in blood compatibility of the material, especially the improvement in blood compatibility of small-diameter artificial blood

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[57] Xu L, Jing ZP. Artificial vascular graft endothelialization of natural. Shanghai Shengwu Yixue Gongcheng Zazhi. 1997;18(2):31-32.
[58] Jing ZP, Xu L. Experimental study of emdothelialization on domestic silk dacron graft. Shanghai Shengwu Yixue Gongcheng Zazhi. 1998;19(1):19-20.
[59] Marko T, Peter B. Vascular graft wall. Eur Paitent. EP0248247, 1987.
[60] Chen BL, Wang DA. Preparation and mechanism of anticoagulatent biomedical polymer materials with blood compatibility. Zhongguo Zuzhi Gongcheng Yanjiu. 2011; 15(29):5507-5510.
[61] Chen BL, Wang DA, Feng LX. Investigation on methods of surface modification of tissue engineering materials: polymer surface group transformation and bioactive molecule immobilization. Zhongguo Zuzhi Gongcheng Yanjiu. 2010;14(3):552-554.
[62] Chen BL, Wang DA, Feng LX. Surface modification of tissue-engineered materials plasma and grafting modification. Zhongguo Zuzhi Gongcheng Yanjiu. 2009; 13(3):587-590.
[63] Chen BL, Wang DA, Feng LX. Application of polymer biomaterials in the tissue engineering. Zhongguo Zuzhi Gongcheng Yanjiu. 2008;12(6):1189-1192.
[64] Chen BL, Wang DA, Feng LX. Polymer porous membrane prepared using thermally induced phase separation. Zhongguo Zuzhi Gongcheng Yanjiu. 2007; 11(40):8217-8219.
[65] Chen BL, Wang DA, Feng LX. Topology of tissue engineered material surface for cell compatibility. Zhongguo Zuzhi Gongcheng Yanjiu. 2007;11(18): 3653-3656.
[66] Chen BL, Wang DA, Feng LX. Effects of physical-chemical properties of tissue engineered material surface on cell compatibility. Zhongguo Zuzhi Gongcheng Yanjiu. 2007;11(1):197-200.
[67] Chen BL, Wang DA, Feng LX. Cytological effect of tissue engineering materials with cell compatibility. Zhongguo Linhchunag Kangfu. 2006;10(45):225-227.
[68] Chen BL, Wang DA, Feng LX, et al. The application of biomedical tissue engineering and the polymer tissue engineering material. Gaoshi Like Xuekan. 2007;27(1): 24-26.
[69] Chen BL, Wang DA, Feng LX, et al. Study on the blood compatibility of biomedical ploymer materials-project of antithromboeicity materials. Suihua Xueyuan Xuebao. 2007;27(1):186-188.
[70] Chen BL, Wang DA, Feng LX, et al. Study on surfaces modify of the tissue engineering materials and application in the tissue engineering. Hulunbeier Xueyuan Xuebao. 2007;15(1):52-54.
[71] Chen BL, Wang DA, Feng LX, et al. Study on the tissue compatibility of biomedical ploymer materials-project of tissue-compatibility materials. Hulunbeier Xueyuan Xuebao. 2006;14(6):34-36.

引言

Biocompatibility is an important problem in the clinical application of biomaterials. Seeding, culturing cells, and preparing polymers suitable for cell growth on the surface of the material (first understanding on the cell-material interactions) consist of a fundamental way to achieve good material biocompatibility. Therefore, studies on biomaterials (tissue-engineered materials) for cell growth not only have positive significance for deeply understanding the cell-material interaction mechanisms, but also have great values for accelerating the clinical application of histocompatible and hemocompatible materials. The biocompatibility of

biomaterials is the key problem that should be solved in the biomedical field. For a long time, people mainly focused on material surface modification when solving the problem of biocompatibility of biomaterials. Nevertheless, the biological environment of materials in biological systems is very complicated due to exposure to body fluids, organic molecules, enzymes, free radicals and cells. Surface modification can limitedly improve hemocompatibility. Therefore, the tissue-engineered technique can be used in in situ culture of human endothelial cells on the surface of the material to induce material endothelialization. This method has become an important way to improve hemocompatibility^[1-4].

In 1952, Voorthees developed the first artificial vascular graft Vinyon N. This artificial blood vessel was successfully used to repair abdominal aortic aneurysm in 17 cases and lower limb aneurysm in one case. In nearly 50 years of research and development, researchers initially dedicated their effort to the development of endogenous materials. The representatives of vascular substitutes are polyethylene terephthalate (trade name: Dacron) and expanded polytetrafluoroethylene (ePTFE), both of which are widely used vascular grafts. However, it is impossible to obtain a graft without any response. The interaction of Dacron and ePTFE with serum and blood cells is both harmful and useful for material endothelialization, and moreover, vascular embolism is inevitable. The researchers are currently working on the synthesis of protein-wrapped graft. Thus, vascular grafts bind different growth factors so as to induce host reactions to the favorable direction. The seeding of endothelial cells is becoming easier. A series of studies have shown that the grafts for seeding endothelial cells present clinical advantages. Ongoing research direction is as follows: new blood vessels and new polymers are immersed within endothelial cell growth factor (ECGF), and/or smooth muscle cell inhibitors, and then gene-modified endothelial cells are seeded. Another graft is absorbable polymeric vessels, which can provide biological dynamics and function of blood vessels. Finally, absorbable polymeric vessels become permanent blood vessels because of the ingrowth of various cells in vivo. The ideal vascular grafts may be formed by the combination of tissue-engineered cells and matrix proteins in vitro.

Currently, indications for a vascular prosthesis implanted in the body contain advanced arteriosclerosis, aneurysmal disease, arteriovenous dialysis and traumatic vascular injury. Vascular replacement or bypass surgery is only applied to large and medium vessels because of graft functional limitations. Barriers to the clinical application of vascular grafts are early embolization and pseudointimal hyperplasia. If these obstacles can be overcome, clinical application of vascular grafts will be used uidely, and replacement of veins and capillaries will be easy^[5-11].

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

材料方法

Data sources

A computer-based online retrieval of PubMed (http://www.ncbi.nlm.nih.gov/PubMed)and Wanfang (http://www.wanfangdata.com.cn)databases was performed for relevant articles publishing from 1963 to 2015. The key words were “biocompatibility, blood compatibility, biomedical materials, biomedical polymer materials” in English and Chinese, respectively. In addition, papers published by the Chinese scholars in foreign journals were also searched, to minimize data loss and maximize sample size.

Inclusion and exclusion criteria

Inclusion criteria

Articles meeting the following criteria were included: (1) articles concerning blood compatibility of biomedical polymer materials: polymer biomaterials used for cardiovascular diseases and their surface modification; (2) articles published recently in the same field or in the authoritative journals.

Exclusion criteria

Repetitive studies were excluded.

Quality assessment

The involved articles were selected in strict accordance with the inclusion and exclusion criteria. Those with the original data were preferred. Duplications, abstracts, and articles of incomplete data were excluded.

Data extraction

Totally 193 articles were retrieved initially, including 44 Chinese literature and 149 English literature. Among them, 122 articles were excluded because of poor correlation with the research purpose and old or repetitive content. Finally, 71 articles were included in result analysis[1-71], addressing the host response, clinical applications, new techniques and legal issues of the existing biomaterials[1-11]; the functions of vascular endothelial cells[12-27]; the tissue-engineered endothelial cells on the surface of grafts[11, 28-36]; the fixation of cell growth- promoting factor on the surface of polymeric biomaterials[37-53]; the endothelialization of the material surface[54-71].

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

讨论

Here, the functions of vascular endothelial cells, tissue-engineered endothelial cells on the surface of grafts, fixation of cell growth-promoting factor on the surface of polymeric biomaterials and endothelialization of the material surface have been analyzed. The biocompatibility, blood compatibility and cytocompatibility of the surface-modified polymer biomaterials are determined based on the endothelial cells in tissue engineering. The endothelial cells in tissue engineering of polymer biomaterials and the research on their biocompatibility and endothelial cell compatibility are crucial for developing novel polymer materials for implantation and intervention in cardiovascular tissue engineering. Through in-depth studies of the types and applications of polymer biomaterials, cardiovascular medical devices and implantable soft tissue substitutes, the differences between the surface and the body will be reflected in the many layers of molecules extending from the surface to the body. Two major factors, surface energy and molecular mobility, determine the body/surface behaviors that include body/surface differences and phase separation. Considering the difference between the body/surface composition, an additional determinant is indispensable, that is, the crystallization behavior of each component. The current research focuses on the biological interactions of grafts. The microenvironment optimization of tissue-graft-blood interface can prevent early thrombosis, suppress late smooth muscle cell hyperplasia, and contribute to the re-externalization of resting endothelium on the blood-contacting surface. Combination of endothelial cells with growth factors to grafts and bioabsorbable template to induce tissue ingrowth is currently one of the most promising studies.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

用于心血管医疗装置的聚合物材料表面构建与生物相容性评价：聚合物生物材料表面的内皮细胞组织工程化改性

Surface construction and biocompatibility of polymer materials as cardiovascular devices: modified tissue-engineered endothelial cells on the surface of polymeric biomaterials

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