Hyaluronic Acid/Alginate Hydrogel Containing Hepatocyte Growth Factor and Promotion of Vocal Fold Wound Healing

Background:: Hepatocyte growth factor (HGF) has been shown to facilitate vocal fold (VF) wound healing. This study was undertaken to determine whether the therapeutic efficacy of HGF could be enhanced by applying it in hyaluronic acid and alginate (HA/ALG) composite hydrogels into VFs after injury in a rabbit model. Methods:: HGF was loaded into HA/ALG composite hydrogel (HGF–HA/ALG) and its in vitro release profile was evaluated. In addition, HGF–HA/ALG was injected into the VFs of rabbits immediately after direct injury and HGF or PBS was injected in the same manner into control groups. Macroscopic features were observed by endoscopy at 3 months post-injury. Functional analyses including mucosal waves of VFs and viscoelastic properties were performed by kymography following high-speed digital imaging and rheometer. Histopathological and immunohistochemical evaluations were also conducted on VFs. Results:: HGF release from HGF–HA/ALG was sustained for up to 3 weeks. Rabbits treated with HGF–HA/ALG showed improved mucosal vibrations and VF viscoelastic properties as compared with the PBS and HGF controls. Histopathological staining revealed HGF–HA/ALG treated VFs showed less fibrosis than PBS and HGF controls, and immunohistochemical analysis demonstrated amounts of type I collagen and fibronectin were lower in HGF–HA/ALG treated animals than in PBS and HGF controls at 3 months post-injury. Conclusion:: HGF containing HA/ALG hydrogel enhanced healing in our rabbit model of VF injury.