title: Functional remodeling after vocal fold injury by small intestinal submucosa gel containing hepatocyte growth factor.
abstract: A biomaterial derived from porcine small intestinal submucosa (SIS) was used in smart drug delivery and tissue remodeling. SIS suspensions were easily formulated by simple mixing with the drug of choice and formed an in situ gel upon injection into tissues, enabling them to act as protein drug depots. This study was conducted to determine whether functional remodeling of an injured vocal fold (VF) could be achieved by hepatocyte growth factor (HGF)-containing SIS in situ-forming gel after VF injury in a rabbit model. To accomplish this, we loaded HGF in SIS suspensions and observed a gradual, sustained release of HGF for at least 21 days in vitro. Evaluation of the in vivo efficacy demonstrated that the HGF and HGF-loaded SIS treated VFs showed improved mucosal healing when compared with the PBS-injected VFs. Histopathological evaluations revealed that treatment with the HGF/SIS group alone successfully ameliorated the deposition of type I collagen and increased synthesis of hyaluronic acids relative to the PBS group at three months post-injury. Functional analyses showed that the HGF/SIS group prevented deterioration of mucosal vibration and induced significant improvement in the mean viscoelastic modulus, but that other groups failed to achieve functional rescue of VF biomechanics. Additionally, the VF oscillation in the HGF/SIS group was superior to that in the HGF group. The results of this study suggest that SIS in situ gel has the potential for use as an HGF delivery carrier for enhancement of wound healing and improvement of functional remodeling following VF injury.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Republic of Korea; Translational Research Center, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Jeong-Seok
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Republic of Korea; Translational Research Center, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Songyi
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Da Yeon
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Republic of Korea; Translational Research Center, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Young-Mo
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Moon Suk
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Republic of Korea; Translational Research Center, Inha University School of Medicine, Incheon, Republic of Korea. Electronic address: jylim@inha.ac.kr.
authors.forename: Jae-Yol
authors.initials: JY
authors.lastname: Lim
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002921:Cicatrix / Q000473:pathology; D003692:Delayed-Action Preparations; D055119:Elastic Modulus / Q000187:drug effects; D004724:Endoscopy; D005109:Extracellular Matrix / Q000378:metabolism; D005782:Gels / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000502:physiology*; D011817:Rabbits; D012212:Rheology / Q000187:drug effects; D034421:Sus scrofa; D014827:Vocal Cords / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology*
chemical_list: D003692:Delayed-Action Preparations; D005782:Gels; D017228:Hepatocyte Growth Factor
keywords: Biomimetic materials; Extracellular matrix; Hepatocyte growth factor; Vocal folds; Wound healing