Vascularization in Tissue Engineering

Vascularization, existing in both physiological and pathological procedures, is a considerable complicated process which is regulated and controlled by a variety of biological factors via diverse pathways and mechanism. It is crucial to understand these processes and factors well if we intend to unveil the mystery of vascularization. More importantly, understanding basic processes offer tools and thinking directions with which researchers are able to design various methods to achieve vascularization, which is called vascular tissue engineering. In this part, major procedures of physical vascularization (vasculogenesis and angiogenesis) and growth factors are introduced, as well as their roles and new research outcomes in vascularization. These factors include vascular endothelial growth factor(VEGF), basic fibroblast growth factor(bFGF), platelet-derived growth factor(PDGF), angiopoietin1, angiopoietin2 and others(junctional molecules, integrals etc.). Lastly, some frequently used markers and testing methods about vascularization research are briefly introduced.

Angiogenesis is a vital step for complete organ engineering, and the microenvironment is one of the four basic elements of tissue engineering. Microenvironment factors such as oxygen content and stress are key dynamic factors that can trigger the variations of angiogenesis. We may induce the formation of beneficial blood vessels and prevent the formation of pathological blood vessels by precisely regulating the microenvironment. In this chapter, we will elaborate the interaction between vascular endothelial cells and the extracellular microenvironment and summarize the influence of various microenvironment factors on angiogenesis. The finding that microenvironment factors play such a concerted role in angiogenesis suggests that incorporating microenvironment factors into tissue engineering might accelerate the development of novel therapeutics.

Past studies have shown that many destructive diseases drive abnormal angiogenesis and progression, such as inflammatory diseases, cancers, rheumatoid arthritis, and atherosclerosis diseases. These diseases, which have a variety of consequences, show some common pathophysiological characteristics, among which the proliferation of endothelial cells, recruitment of immune cells, and high-expression of angiogenic factors play a key role. At the same time, local hypoxia, inflammation, senile, and local ischaemia cause adverse consequences such as abnormal vascularisation. Abnormal blood vessels usually include vascular structural abnormalities, abnormal endothelial cells, excessive vascular permeability, vascular dysfunction, etc. The pathological microenvironment is related to abnormal vascularisation and further aggravates the abnormality of vascularisation. Therefore, this review will be helpful for further study of vascularised tissue engineering.

Since endothelial cells are not able to create capillaries by themselves, proangiogenic factors are indispensable for endothelial cells to migrate and form microcapillaries. Thus, exogenous proangiogenic compounds are needed to improve the formation of microcapillary-like structures. Multiple forms of cell-cell interactions could result in the production of essential proangiogenic factors in co-culture systems. Many studies have examined that the co-culture systems of endothelial cells and other cell types, such as osteoblasts or mesenchymal stem cells (MSCs), can facilitate the formation of capillary-like structures. The focus of this chapter is threefold: (1) Informing the biological function of vascularization in the physiological environment. (2) Introducing typical co-culture system models for vascularization. (3) Identifying the proangiogenic factors that play crucial roles in the formation of capillary-like structures.

In the process of tissue engineering vascularization, as one of the three major factors of tissue engineering, scaffold materials play a vital role in the various processes of vascularization. As a starting point, this chapter first introduces the reader to several strategies for scaffolding materials to promote vascularization. It basically describes the reasons for the use of scaffold materials in vascularization and the necessity of scaffold materials in tissue engineering vascularization. Then we will focus on how to properly use the scaffold material. The design of the scaffold material itself is a key factor in the function of the material, and the scaffold material with ideal biological properties can make the process of vascularization more effective. Factors such as the topology of the material and the physical and chemical properties of the material affect the success rate of vascularization to varying degrees. We hope that readers can obtain the basic knowledge and principles of stent design from this chapter. Finally, a number of fresh ideas have emerged for the design of tissue engineered vascular materials, such as new material handling methods, new ways of combining cells, and so on, which have improved the vascularization process to varying degrees. Scaffold materials have shown attractive prospects and great possibilities in vascular tissue engineering. Previous studies have found many materials associated with vascularization, but there are also many problems to be solved. With the development of materials science and engineering, it is believed that there will be new vascular stent materials with better performance and more suitable for vascularization in the future.