The ground substance occupies the space between the cells and fibers of dermal connective tissues. It is an amorphous viscoelastic gel in which the other components (cells and fibers) are held in place . Ground substance consists largely of proteoglycans and glycosaminoglycan (GAG) and large amount of water that are synthesized and secreted by fibroblast. Water can make up sixty to seventy percent of the ground substances, and it is retained there because of the glycosaminoglycan (GAGs). Proteoglycans are large macromolecules consisting of a core protein to which many glycosaminoglycan (GAG) molecules are covalently attached. Glycosaminoglycan (GAG) are long-chained polysaccharides made up of repeating disaccharide units. One of the sugars in each disaccharide unit is a hexosamine (also called glycosamine), hence the name GAG. Many of the sugars in GAGs have sulfate and carboxyl groups, which makes them highly negatively charged. The high density of negative charges make proteoglycan and GAGs hydrophilic that are capable to bind to 1000 times its volume of water, forming a hydrated gel with viscous property. This gel permits the rapid diffusion of water-soluble molecules but inhibits the movement of large molecules. There are seven distinct GAGs identified based on differences in the specific sugar residues, the nature of the linkages and the degree of sulfation. Four types of GAGs also comprise of GAG components of proteoglycans: chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS). Sometimes, nonfibrous glycoproteins also considered as part of the composition of the ground substance as well. Nonfibrous glycoproteins synthesized and secreted by skin fibroblast is not as well defined as compared to that of proteoglycan.
Hyaluronic acid (HA or Hyaluronan ) is the most important and abundant GAG in the dermal connective tissue. It differs in several aspects from typical GAGs. It is extremely long and rigid, consisting of a chain of several thousand sugars, as opposed to several hundred or less in other GAGs. Proteoglycans can indirectly bind to HA via linker proteins, to form giant macromolecules. Various researchers have estimated that HA can bind one thousand to eight thousand times its volume of water. Another estimate suggests each HA protein in the extracellular matrix has fifteen thousand molecules of water associated with it!
The water binding capacity of ground substance give skin its plump characteristics. Loss of water or dehydration is one of the reason skin become wrinkled and laxed. The hydrated gel and semi-liquid property of the dermal connective tissue contribute to skin’s biomechanical property such as viscoelasticity as well as the ability to resist compression (incompressibility) of the skin. Ground substance contribute largely to the viscous component of skin’s nonlinear viscoelasticity when collagen fibers slide and realign in response to tensile (stretching) stress. However, a cyclic loading and unloading of the tissue is important to maintaining health.
Beside its strong water binding capacity, the protein core of the proteoglycans are capable to interact with other components (cells and fibers) of the matrix, thereby is important in maintaining and organizing the matrix structure, influencing fibroblast proliferation, differentiation and migration, and regulating collagen fibrillogenesis. Two of the most abundant proteoglycans in the skin is decorin and versican. Decorin can bind to collagen type I, III whereas versican can bind to elastic fibers.
When the extracellular matrix is well hydrated, cells, nutrients, and other components of the matrix can move about freely. Waste products can migrate out of the matrix into the blood or lymphatic system to be removed from the body. The ground substances are also helpful in resisting the spread of infection and are a part of immune system barrier.
During the aging process, the ability of the body (fibroblast) to create HA, other GAGs and proteoglycan diminishes. Fewer fibroblasts are available in skin and amount of senescent fibroblast increases with aging. As a consequence, the extracellular matrix becomes filled more and more with disorganized and damaged fibers that are cross-linked. As a result, skin’s biomechanical properties changes, causing loss of elasticity, tensile strength, and incompressibility and less open to the flow and migration of the other components such as immune cells in response to infection in the dermis.
Hyaluronic acid (HA) anti-aging dermal filler are widely used to treat wrinkles and facial lines that are dehydrated. Hyaluronic acid is also a common anti-wrinkle ingredients in the formulation of topical anti-aging creams combined with other anti-aging ingredients.