In connective tissue, ground substance is the non-cellular components of extracellular matrix which contain the fibers.
It is usually not visible on slides, because it is removed during the preparation process.
Cells are surrounded by extracellular matrix in tissues, which acts as a support for the cells. Ground substance traditionally does not include collagen but does include all the other proteinaceous components, including proteoglycans, matrix proteins and, most prevalent, water. The non-collagenous components of extracellular matrix will vary depending on the tissue in which it is found.
Ground substance is amorphous, gel-like, and is primarily composed of glycosaminoglycans (most notably hyaluronan), proteoglycans, and glycoproteins.
The meaning of the term has evolved over time.
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