ReviewThree-dimensional insights into dermal tissue as a cue for cellular behavior
Introduction
Scar formation after injury is a big problem, which take negative influence on the skin function and esthetic appearances. Up to now, many researchers have explored the mechanism in many directions, such as various molecules, cytokines, and signal pathways [1], [2], [3], [4]. However, skin wound healing is a dynamic and highly regulated process of cellular, humoral and molecular mechanisms which begins directly after wounding and might last for years, thus it cannot imagine that that only one, or several of these molecules involved in the healing process can have a substantial impact on diminishing the scar formation [5], [6].
Another series of research showed that scar formation is related to the loss of integrity in dermal tissues [7], [8], [9], [10]. In dermal tissues, the extracellular matrix (ECM) is composed of collagens and other macromolecules. Collagen is the most and acts as backbone in dermal tissues. The structure of dermal tissue acts not only as a stationary scaffold to support the mechanical stability of skin, arrange the cells, and keep cytokines and other proteins within dermal tissues [5], [11], [12], but also as a dynamic scaffold to regulate the tissue microenvironment and cellular behavior (morphology and function) within it [13], [14], [15], and plays roles in embryogenesis, tissue regeneration, and wound healing [16], [17]. When the integrity of dermal tissues lost, especially when a skin injury involves the deep dermal tissues, it cannot effective regulate the cell behavior, and hence the scars, which are morphologically irregular arrangement of collagen tissues, occurred after wound repaired [7], [8], indicating the very important role of structure, especially the 3D structures, in scar formation. However, how does the 3D structure take influence in cell behavior and scar formation and what is the 3D structure of the dermal tissues? Although the concept of “contact guidance” is well established, many tissue engineering products have been developed. The question about how the “contact” guides the cellular behavior is still need to clarify. When a cell contacts the surface of the structure, what element of the surface can regulate the cells? Among the surface, there are chemical components and physical characteristic. Although chemical components can influence the cell behavior by concentration gradient, the physical characteristic seems to be more important for its capability of locating the chemical components. Among the physical characteristic, which is more important? It is noted that the surface do not smoothly even, it is undulate microscopically and similar to be composed of dots, the dots could virtually line with lines. The angles exit between the lines, suggesting the angle might plays a role in contact guidance.
Section snippets
From the ECM backbone to cellular behavior
Since the backbone is characterized as its high porosity, pore size, and inter-pore connectivity, the differences in pore size are thought to have the capability of influencing cell behavior [6], [7], [18], [19]. Then how does pore size affect cellular behavior? Although many experiments tried to answer this question, [18], [19], the results could not be extrapolated. This is partly because the complex manner is involved many interactions which have not been found and are nonlinear feedback.
Conclusion
Cell behavior has been demonstrated to be regulated by various angles, determined both by curvature, the feature of the backbone within the ECM, and by neighboring adhesive molecules on the surface of the backbone of the ECM. The concept of the angle regulation might be universal in the microenvironment and might be one of the mechanisms underlying contact guidance, which is consistent with Mogilner [42].
Summary
ECM is a complex mixture of molecules arranged in unique 3D patterns that mediate structural and/or biological properties, which regulate the cell behavior by the combination of varies angle regulation. The smaller, delicate angles, which in the normal ECM, might guide the normal cell behavior than the bigger, tough angles, which in the ECM of scar tissue. However, even given the view that the structure of dermal tissue could play an important role in cell behavior, the role of the composition
Affix
- 1.
The cell and the curvature of the pore: Curvature could represent the size of the pore; the curvature is defined as the degree of curving of a line or surface. It is also measured as the derivative of the inclination of the tangent with respect to arc length at the point on a curve (equation: 180l/2πr, where l is the length of cell adhered to the pore and r is the radius of the pore; Fig. 1A). From this equation, we find that a larger diameter pore size has the smaller angle of curvature, and a
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the papers.
Acknowledgments
The research was supported by the National Natural Science Foundation of China (30872685, 81272110, 81071566), the Major State Basic Research Development Program of China (Grant No. 2012CB518105).
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