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Online ISSN 2212-5469

ORIGINAL ARTICLE

Hyaluronic Acid/Alginate Hydrogel Containing Hepatocyte Growth Factor and Promotion of Vocal Fold Wound Healing Jeong-Seok Choi1

•

Se Heang Oh2 • Young-Mo Kim1 • Jae-Yol Lim3

Received: 24 April 2020 / Revised: 17 May 2020 / Accepted: 7 June 2020 Ó The Korean Tissue Engineering and Regenerative Medicine Society 2020

Abstract 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 postinjury. 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. Keywords Hepatocyte growth factor  Hyaluronic acid  Alginate  Vocal fold  Wound healing

1 Introduction

& Jae-Yol Lim [email protected] 1

Department of Otorhinolaryngology - Head and Neck Surgery, Inha University School of Medicine, 100 Inha-ro, Michuhol-gu, Incheon 22212, Republic of Korea

2

Department of Nanobiomedical Science, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam 31116, Republic of Korea

3

Department of Otorhinolaryngology, Gangnam Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea

Vocal folds (VFs) are connective tissues composed of a complex extracellular matrix (ECM). They have a unique layered structure, the biomechanics of which are determined by ECM components that importantly determine voice quality. VFs scars are the result of injuries caused by, for example, vocal abuse, surgery, or inflammation, and lead to VF vibration reduction and possibly dysphonia [1]. These voice disorders lead to changes in the tissues of the vocal cord mucosa. Excessive collagen deposition and reduced hyaluronan or elastin have been observed in the lamina propria [2]. VFs scars is o