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Reticular Dermis01:15

Reticular Dermis

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The papillary and reticular dermis are the two layers of the dermis. They are made of connective tissue with fibers of collagen extending from one to the other, making the border between the two somewhat indistinct. The dermal papillae extending into the epidermis belong to the papillary layer, whereas the dense collagen fiber bundles below belong to the reticular layer.
Reticular Layer
Underlying the papillary layer is the much thicker reticular layer, composed of dense, irregular connective...
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Cultivating a Three-dimensional Reconstructed Human Epidermis at a Large Scale
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Biomimetic human skin model patterned with rete ridges.

Maxwell B Nagarajan1,2, Alexander J Ainscough1,2, Daniel S Reynolds1,2

  • 1John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, United States of America.

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|September 21, 2023
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Summary

Researchers developed a novel micro-stamping technique to create realistic human skin models with rete ridges. This advanced 3D skin model accurately mimics skin structure and function for various testing applications.

Keywords:
biomimetic skin modeldermisepidermisrete ridgestelocollagen

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Area of Science:

  • Biomaterials Science
  • Tissue Engineering
  • Dermatology

Background:

  • Human skin possesses rete ridges, which are epidermal-dermal undulations crucial for mechanical and biological functions.
  • Existing human skin models typically lack these rete ridges, featuring a flat epidermal-dermal interface.
  • This structural simplification limits their ability to fully replicate native skin physiology.

Purpose of the Study:

  • To develop a micro-stamping method for fabricating human skin models with controlled rete ridge geometry.
  • To create a biomimetic 3D skin model that enhances the mechanical properties and biological function of traditional models.
  • To assess the compatibility and utility of this model for various biological and toxicological testing applications.

Main Methods:

  • A micro-stamping technique was employed to pattern rete ridges into human skin models.
  • Telocollagen-fibrin matrices, with and without crosslinks, were utilized to maintain micropatterned features during culture.
  • The model's epidermal structure was validated using specific cellular markers (cytokeratin 14, p63, Ki67, cytokeratin 10).
  • The basement membrane was confirmed with laminin and collagen IV.
  • Two distinct keratinocyte cell lines (neonatal and adult diabetic) were tested for compatibility.
  • An irritation test using sodium dodecyl sulfate was performed to evaluate epidermal barrier function.
  • Gene expression analysis was conducted to compare 2D and 3D culture conditions and donor differences.

Main Results:

  • The micro-stamping method successfully produced human skin models with patterned rete ridges of defined geometry.
  • The telocollagen-fibrin matrices effectively preserved the micropatterned features during longitudinal culture.
  • The fabricated epidermis displayed characteristic markers of native human skin, including a distinct basal and suprabasal layer.
  • The model demonstrated compatibility with both neonatal and adult diabetic keratinocyte cell lines.
  • The model's epidermis effectively prevented rapid penetration of sodium dodecyl sulfate in an irritation test.
  • Gene expression analysis revealed significant differences between 2D and 3D cultures and between the two donor cell lines.

Conclusions:

  • The developed micro-stamping method enables the creation of biomimetic human skin models with functional rete ridges.
  • This 3D skin model offers improved structural and functional relevance compared to traditional flat models.
  • The model shows promise for applications in drug and cosmetic testing, disease modeling, wound healing research, and aging studies.