Investigating the Role of Hyaluronic Acid Synthase-1 Overexpression and Increased Hyaluronic Acid Production on Tendon Healing Properties
Tendon healing in adults following injury is often complicated by scar formation that is related to the inflammation that occurs following tendon injury. Formation of peritendinous adhesions can inhibit the normal gliding motion of the tendon and lead to functional disability. Investigating the unique environment of fetal tissue healing may help address these clinical problems.
Compared to adult tissue healing, fetal tissue heals through a regenerative process in the absence of scar formation. Persistent elevation of hyaluronic acid (HA) levels is one of the unique properties of the fetal tissue environment that could contribute to scarless healing. By modulating the adult tissue healing process to more closely approximate the fetal healing environment, specifically the elevated levels of HA, structural, compositional, and mechanical properties closer to native tissue may be attainable.
Gene therapy offers a method by which levels of a HA can be sustained at an elevated level. Using this method, an exogenous gene can be transferred into the genome of a host cell. Using a vector carrying the gene for hyaluronic acid synthase-1 (HAS-1), the enzyme responsible for producing HA, persistently elevated HA levels can be attained. Previous studies using injection of a lentiviral vector carrying the HAS-1 gene in adult dermal wounds have replicated regenerative fetal tissue healing properties.
Using a lentivirus-mediated gene transfer of HAS-1 to tendon fibroblasts in vivo and a well-established mouse patellar tendon injury model, we can overexpress HAS-1 and measure the effects of increased hyaluronic acid on tendon injury and healing. Our goal is to determine effects of HAS-1 overexpression and increased HA production on mechanical, histological, immunohistochemical, and biochemical properties of injured tendon.