Volume exclusion agent to enhance formation of extracellular matrix

A method of enhancing the formation of extracellular matrix in culture. Cells in culture secrete most of the collagen into the media as unprocessed procollagen, i.e., the cells do not convert procollagen to collagen. In contrast, normal extracellular matrix deposition involves procollagen processing to collagen, fibril assembly and deposition into the cell layer to form a collagenous extracellular matrix. The addition of certain growth factors and the addition of a thin layer of a certain volume exclusion agent on top of the cells dramatically enhances the conversion of procollagen to collagen and will increase the amount of collagen and extracellular matrix associated with the cells. This invention advances bioengineering of connective tissues for medical applications that require an extensive and functional extracellular matrix with high tensile strength such as those in the cornea stroma, skin, tendons, ligaments, articular cartilage and the intervertebral disks.