Regeneration of Mammalian Skin

Abstract

Regeneration and repair of tissue injury in mammalian skin is an intricate process in which cellular, biochemical and molecular interactions occur. These interactions are the foundations of new therapeutics and approaches designed to facilitate tissue repair. The ultimate goal is to regenerate skin such that the complete structural and functional properties of the wounded area are restored to the levels before injury without a scar. Novel pharmaceutical approaches to scar reduction are under development, with the furthest progressed being avotermin (Juvista; transforming growth factor beta 3 (TGFβ3)). In addition, new synthetic biomaterials are constantly being developed that may in future enable some control over the capacity for tissues to regenerate by manipulating stem cells, cell adhesion, growth and differentiation for optimal tissue development. The success of these new approaches to skin regeneration is likely to be underpinned by the manipulation of the mechanisms responsible for wound repair and regeneration.

Key Concepts:

  • Like other animals such as newts and salamanders, mammals have the ability to regenerate tissues.

  • Many wound signals probably control more than one cell activity, and regeneration probably constitutes an orchestrated response to a mixture of such signals.

  • The processes involved during wound healing can trigger an embryonic state in the skin which makes it receptive to regenerative cues and signals.

  • New approaches to skin regeneration are likely to be underpinned by our understanding of the mechanisms responsible for wound repair.

  • Skin wounds on early mammalian embryos heal perfectly with no scars, whereas wounds to adult mammals scar.

  • The growth factor profile in a healing embryonic wound is very different from that in an adult wound.

  • TGF‐β3 has the ability to elicit a scar‐reducing effect and thus a regenerative healing response in mammalian skin.

  • Scars can have a significant psychological impact on patients, irrespective of whether or not they are hidden by clothing.

  • Scarring may no longer be an inevitable consequence of modern injury or surgery; a pharmaceutical approach to the prevention of human scarring is now possible.

Keywords: wound healing; scarring; transforming growth factor beta; epithelialisation; angiogenesis; growth factors; regeneration; skin

Figure 1.

The phases of wound healing in the skin involve a number of overlapping phases, including injury and coagulation (a), inflammation (b), proliferation and epithelialisation (c), angiogenesis and matrix deposition during the remodelling and maturation phases (d). Various growth factors and cytokines are expressed during these phases such as transforming growth factor beta (TGFβ1,‐2, ‐3), TGF alpha (TGFα), platelet‐derived growth factor (PDGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), tumour necrosis factor alpha (TNFα) and interleukin‐1 beta (il‐1β), interleukin 6, matrix metalloproteinases (MMP's), urokinase (uPA) and tissue type plasminogen activator (tPA).

Figure 2.

Scarring is conserved across species. Scarring response in mice 70 days following a 1 cm fullthickness incisional wound to the dorsum at the macroscopic (a) and microscopic (b) levels. Scarring response in rats 70 days following a 1 cm full thickness incisional wound to the dorsum at the macroscopic (c) and microscopic (d) levels. Scarring response in pigs 168 days following a 1 cm full thickness incisonal wound to the dorsum at the macroscopic (e) and microscopic (f) levels. Scarring response in humans 365 days following a 1 cm full thickness incisional wound to the inner aspect of the upper arm at the macroscopic (g) and microscopic (h) levels. Arrows on both the macroscopic and microscopic images define the scar edges.

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Metcalfe, Anthony D, and Ferguson, Mark WJ(Jan 2011) Regeneration of Mammalian Skin. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001109.pub2]