Page 106 - Tailoring Electrospinning Techniques for Regenerative Medicine - Marc Simonet

CHAPTER 5
a distinct role for mechanical and biochemical regulatory factors provided by the extracellular matrix environment.30,31 The composition, architecture and mechanical properties of the extracellular matrix act in concert to provide the necessary cues in regulating tissue development. The sensors and e ectors in this process are the valvular cells. During early tissue formation they respond to environmental stimuli by growing and dividing (proliferation) and by laying down extracellular matrix components.32 Later, they respond by changing their own morphology and function (di erentiation) and by modifying the composition and organization of the extracellular matrix – a process referred to as matrix remodeling.33 Thus, the cells are the key modulators of tissue formation and remodeling and in this way actively control and maintain tissue architecture and mechanical functioning. Under non-pathologic conditions heart valves show an intriguing adaptive response to changes in their environment. In case of functional demand changes, the cells rapidly remodel the ECM to meet the new requirements. They presumably do this by changing the production of matrix components, by secreting matrix enhancing or degrading products (MMPs) as well as their inhibitors (TIMPs), and by applying traction forces to the deposited fibers.34
The interactions between the cells and the matrix environment are two-fold: on the one hand, the matrix controls cell and tissue fate
(cell shape, proliferation, di erentiation, motility, alignment) through its 3D architecture and focal adhesion organization. On the other hand, the cells influence the matrix by applying traction forces and by changing the matrix turnover. How the cells sense and a ect their environment is only partly known. Several ‘mechanosensors’ and receptors for biochemical cues have been identified35–37 and various signaling pathways that translate the sensed signals into cellular actions have been proposed,38,39 though not specifically for heart valves. A thorough understanding of the interactions between cells and their microscopic matrix environment in developing and remodeling tissues, however, is lacking. It is nevertheless evident that sca old materials are an important tool to mimic these interactions during tissue engineering strategies and to systematically study these interactions during in-vitro and in-vivo experiments.
On a microscopic scale a diversity of environmental factors contributes to the overall control of cell fate, either through physical or through molecular interactions, aimed to guide cell morphology and behavior (adhesion, migration, proliferation, di erentiation) as well as tissue morphogenesis. These environmental factors, which together constitute the so called ‘cellular niche’, include: the presence and density of cell adhesion molecules, growth factors and morphogens, local visco-elastic properties, local fibrillar matrix
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