The scaffolding or structure of the matrix, is made up of the collagen lattice, mainly collagen type I, and ground substance, and migrating cells.  Collagen is the major building block of connective tissue, accounting for 30% of total body protein.  The mature collagen fiber found in dermis is composed of collagen units which form a very strong filament.  The fibers are formed outside the fibroblast, oriented by matrix signals and through proteoglycan contact.  Of the many types of collagen, type I is the most abundant in normal skin.  Type III collagen is less pliable and more common in scar.  Besides dermal structure, collagen type I provides a contact orientation for dividing and migrating epithelial cells. This cell guidance system allows for more organized healing process and less scar.  Elastin, another structural protein, provides elasticity to the dermis and the healing wound.

The matrix or ground substance is composed of glycosylated proteins found both on cell surfaces and in the extracellular tissue space.  Other key components include hyaluronic acid and heparin sulfate produced by the fibroblast.  The glycosaminoglycans (GAGs) are polysaccharides composed of repeating disaccharide units.  The GAGs are attached to a core protein producing a proteoglycan.  Chondroitin sulfate and heparin sulfate are two such matrix elements.  Glycosaminoglycans (GAGs are essential for normal dermal structure and function.  Functions of the ground substance include a scaffold for protein deposition, a conduit for nutrients, a deactivator of proteases and a guidance system for cell migration. (Summary Table)  

A number of biologically active compounds are present in matrix which direct the healing process.  The main active components are fibronectin, hyaluronic acid and growth factors.

 Fibronectin is an adhesion protein, produced mainly by fibroblasts and macrophages.  It is a large glycoproteins found in all tissues and plasma.  One of its key functions is an attachment protein to  collagen type I.  In addition, this protein is the key adherence molecule attaching epithelial and endothelial cells at cell junctions.  Fibronectin also stimulates epithelial cell migration, spreading and orientation as well as acting as a chemo attractant for fibroblasts.

Hyaluronic acid (HA) is a major carbohydrate component composed of a simple repeated disaccharide in a co-polymer structure.  Hyaluronic acid, in its native macromolecular form does provide a structural property.  However, it also affects cell behavior by directing proper cell alignment.  HA is also found as fragments which have direct actions on all dermal cells affecting all phases of wound healing through receptor binding events.

Growth Factors: A group of macrophage produced polypeptides (protein fragments direct the healing process within the matrix) have many actions including the stimulation of cell proliferation and cell migration.  These messages cause the cells to react to product structures.  For example, these messages cause epithelial cells to produce epidermis and cause fibroblasts to make collagen.

A large variety of “polypeptide growth factors” have been identified and named.  Although each has a predominant function on a specific cell, it now appears that essentially all growth factors have a multitude of actions.  Monocytes and macrophages are thought to be the main producers of growth factors; however, all skin cells, including fibroblasts and keratinocytes, play an important role in secreting growth factors.

Once formed, the growth factors can be rapidly deactivated by wound proteases; i.e., those released from white cells, mainly neutrophils.  The wound is activated to produce excess proteases, probably in an attempt to break down surface dead tissue.  Surface exudates developing on an open wound is a rich source of such proteases, especially the class of metalloproteases.  Glycosaminoglycans also actively participate in healing by deactivating excess proteases and by acting as a conduit for nutrients.

Summary: Extra-cellular matrix components

Function of matrix components:

Collagen (protein)

• scaffold for cell migration and matrix deposition

• cell guidance

• tissue elasticity

• cell adherence properties

• conduit of healing factors
• deactivator of proteases
• scaffold or foundation for dermal elements

• cell to cell adherence

• contact orientation for cells
• increases epithelial cell division, migration
• chemo-attractant for fibroblasts, macrophages

• maintaining matrix moisture

• decreases inflammation (native macromolecule)
• stimulates healing (HA fragments)
• proper cell alignment

• stimulates all phases of wound healing