The effect of endogenous overexpression of hyaluronan synthases on material, morphological, and biochemical properties of uncrosslinked collagen biomaterials

Hyaluronan is an essential component of the native extracellular matrix that has often been added exogenously to biomaterials. The role of endogenously produced hyaluronan on soft tensile tissue mechanics, however, has been largely overlooked. To investigate this aspect of hyaluronan using a cell-mediated approach, cells overexpressing the hyaluronan synthases (has), namely has-1, has-2, has-3 or the empty vector control LXSN, were seeded within collagen gel scaffolds. The resulting engineered tissues were grown under static tension for 6 weeks. Following 6 weeks of culture, the samples were characterized to assess collagen gel contraction, matrix organization, production of hyaluronan, and tissue material properties. The engineered tissues containing cells transfected to overexpress one of the has isozymes had significantly increased retention of hyaluronan within the scaffold; elevated hyaluronan secretion into the culture medium (all but has-2); reduced contraction; reduced collagen density; and significantly altered material properties compared to the LXSN controls. These results indicate that the cell-mediated endogenous overproduction of hyaluronan within biomaterials alters their material, morphological and biochemical characteristics. This investigation, the first to examine the role of endogenously produced hyaluronan in engineered tissue mechanics, suggests that overproduction of hyaluronan in soft connective tissues can transform their biological and biomechanical functionality.