Biomedical Engineering Reference
In-Depth Information
responses are discussed. In so doing, the ingredients of wound repair (that
contribute to wound contraction) and scar formation will be emphasized. The
essential architecture and cellular components necessary for a regenerative proc-
ess is explored next. Finally, these ingredients, so defined, are analyzed in the
context of available biodegradable matrices that seek to promote cutaneous tissue
regeneration.
4.2 Skin microanatomy and physiology
In understanding repair and regeneration, it is essential to be familiar with the
anatomic and physiologic functions of normal skin. Histologically, skin is divided
into two functionally interdependent layers: epidermis and dermis.
1
Skin is com-
posed of acellular matrix components and a variety of cells, which together,
subserve a myriad of protective functions, including mechanical and
photoprotection, immunosurveillance, nutrient metabolism and repair.
4.2.1
Epidermis
The majority of the epidermis is composed of mostly keratinocytes (>90%), while
the remainder consists of small subpopulations of melanocytes, Langerhans cells,
neuroendocrine (Merkel) cells and unmyelinated axons. Architecturally, the
undersurface contains downward ridge-like projections (rete ridges) that interdigi-
tate with upward-projecting dermal mesenchymal cones (papillary dermis.) A
three-dimensional reconstruction of the undersurface would therefore, resemble a
thick-chambered honeycomb.
The epidermis is subdivided into four basic layers (from deep to superficial):
basal cell layer, spinous cell layer, granular layer and cornified (horny) layer. Cells
forming these layers are bound together by complex membrane-associated plaques
called desmosomes. Desmosomes anchor and unite cytoskeletal components of
adjacent epidermal cells. Important molecules critical to keratinocyte-keratinocyte
bonding (adhesion) includes cadherins, desmogleins, and desmocollins.
The basal cell layer (deepest) is made up of a single 'sheet' of cells that interfaces
with the underlying basement membrane, to which they are attached to via
membrane-associated plaques (hemidesmosomes.) At the molecular level, struc-
tural proteins and integrin (transmembrane receptor protein)-ligand interactions
mediate the anchoring of the epidermal layer to the subjacent dermis. In normal
skin, most epidermal mitotic activities take place in the basal cell layer and,
accordingly, defects in homeostasis of this layer may have critical effects on the
maintenance of an intact and viable epidermis. The basal cell layer contains a
subpopulation of slow-cycling stem cells that are possibly of critical importance to
the regenerative potential of human skin.
Post-mitotic keratinocytes rest on top of the basal cell layer, with the youngest
in the spinous layer and oldest in the cornified layer. As keratinocytes 'mature' and
