Elsevier

Burns

Volume 40, Issue 2, March 2014, Pages 191-199
Burns

Review
Three-dimensional insights into dermal tissue as a cue for cellular behavior

https://doi.org/10.1016/j.burns.2013.09.015Get rights and content

Abstract

Scar formation after injury is a big problem, which influences the skin function and esthetic appearances. Recent researchers have hinted many directions, one of which has shown that scar formation is related to the loss of integrity in dermal tissues. The structure of dermal tissue, which contains mostly collagen, is not only crucial for the mechanical stability of skin, but also acts as a dermal template, providing contact guidance for regulating cell behavior and restoring normal structure and function to skin that has been damaged by injury. These findings suggest a series of questions. How does contact guidance regulate cell behavior? What is the three-dimensional (3D) architecture of the dermal tissue? How does the native 3D architecture influence cell behavior in vivo? In this paper, combing our recent research, we will review the recent advances in this field, that is, the phenomenon of contact guidance and explore the possible mechanism behind it.

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).

References (65)

  • H. Tsuruta et al.

    Experimental approaches for solution X-ray scattering and fiber diffraction

    Curr Opin Struct Biol

    (2008)
  • K. Gelse et al.

    Collagens-structure, function, and biosynthesis

    Adv Drug Deliv Rev

    (2003)
  • T.J. Wess et al.

    A consensus model for molecular packing of type I collagen

    J Struct Biol

    (1998)
  • V. Ottani et al.

    Hierarchical structures in fibrilar collagens

    Micron

    (2002)
  • V. Ottani et al.

    Collagen structure and functional implications

    Micron

    (2001)
  • J.A. Sherratt et al.

    Theoretical models of wound healing: past successes and future challenges

    C R Biol

    (2002)
  • R. Martin et al.

    Liquid crystalline ordering of procollagen as a determinant of three-dimensional extracellular matrix architecture

    J Mol Biol

    (2000)
  • D.C. Carrer et al.

    Pig skin structure and transdermal delivery of liposomes: a two photo microscopy study

    J Control Release

    (2008)
  • T. Abraham et al.

    Quantitative assessment of forward and backward second harmonic three dimensional images of collagen Type I matrix remodeling in a stimulated cellular environment

    J Struct Biol

    (2012)
  • S.F. Badylak et al.

    Extacellular matrix as a biological scaffold material: structure and function

    Acta Biomater

    (2009)
  • R. Kemkemer et al.

    Cell orientation by microgrooved substrate can be predicted by automatic control theory

    Biophys J

    (2006)
  • J. Cole et al.

    Early gene expression profile of human skin to injury using high-density cDNA microarrays

    Wound Repair Regen

    (2001)
  • M. Schafer et al.

    Transcriptional control of wound repair

    Annu Cell Dev Biol

    (2007)
  • S. Werner et al.

    Regulation of wound healing by growth factors and cytokines

    Physiol Rev

    (2003)
  • C. Huang et al.

    Mechanosignaling pathways in cutaneous scarring

    Arch Dermatol Res

    (2012)
  • D.G. Simpson

    Dermal templates and the wound-healing paradigm: the promise of tissue engineering

    Expert Rev Med Dev

    (2006)
  • J.M. Reinke et al.

    Wound repair and regeneration

    Eur Surg Res

    (2012)
  • S.L. Lu et al.

    Study on the mechanism of scar formation: epidermis template defect theory

    Chin J Burns

    (2007)
  • Y.K. Liu et al.
  • C.S. Dunkin et al.

    Scarring occurs at a critical depth of skin injury precise measurement in a graduated dermal scratch in human volunteers

    Plast Reconstr Surg

    (2007)
  • D.H.M. Pauline et al.

    Differences in collagen architecture between keloid, hypertrophic scar, normotrophic scar, and normal skin: an objective histopathological analysis

    Wound Repair Regen

    (2009)
  • R. Raghow

    The role of extracellular matrix in postinflammatory wound healing and fibrosis

    FASEB J

    (1994)
  • Cited by (6)

    View full text