title: Controlled Release of Hepatocyte Growth Factor from MPEG-b-(PCL-ran-PLLA) Diblock Copolymer for Improved Vocal Fold Regeneration.
abstract: An in situ-forming gel system comprised of diblock copolymer formed from polyethylene glycol (PEG) and polycaprolactone (PCL) {MPEG-b-(PCL-ran-PLLA)} could be used in controlled drug delivery for tissue remodeling. The purpose of this study is to demonstrate favorable vocal folds (VF) regeneration by using MPEG-b-(PCL-ran-PLLA) diblock copolymers (C97L3; CL/LA ratio 97:3) incorporating hepatocyte growth factor (HGF). Gradual release of HGF from C97L3 is detected and biochemical properties of released HGF are maintained. A scar is made with microscissors on both VFs in 32 rabbits, followed by injection of HGF-only, C97L3-only, or HGF-C97L3 composite gel in the left side VF, while the right side VF is left untreated. In vivo fluorescence live imaging system demonstrates that C97L3 enables the sustained release of injected HGF in the scarred VF for 12 weeks. The histological analysis shows increased glycosaminoglycan including hyaluronic acid accumulation and decreased collagen deposition. Videokymographic analysis shows more favorable vibrations of HGF-C97L3 treated VF mucosa, compared to other treatment groups. In conclusion, the controlled HGF release helps to regulate extracellular matrix synthesis, and leads to the eventual functional improvement of the scarred VF.
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, 16499 Suwon, Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, 16499 Suwon, Korea.
authors.forename: Yeon Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, 16499 Suwon, Korea.|Department of Molecular Science and Technology, Ajou University, 16499 Suwon, Korea.
authors.forename: Ju Kyeong
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, 16499 Suwon, Korea.
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Song
authors.affiliation: Department of Molecular Science and Technology, Ajou University, 16499 Suwon, Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, 16499 Suwon, Korea.
authors.forename: Moon Suk
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, 16499 Suwon, Korea.|Department of Molecular Science and Technology, Ajou University, 16499 Suwon, Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, 16499 Suwon, Korea.|Department of Molecular Science and Technology, Ajou University, 16499 Suwon, Korea.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations; D004285:Dogs; D065546:Drug Liberation; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005453:Fluorescence; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D061985:Madin Darby Canine Kidney Cells; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects*; D014732:Vibration; D014827:Vocal Cords / Q000502:physiology*
chemical_list: D003692:Delayed-Action Preparations; D011091:Polyesters; C000623328:mPEG-b-(PCL-ran-PLLA); C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols; D017228:Hepatocyte Growth Factor
keywords: extracellular matrix; hepatocyte growth factor; in vivo fluorescence live imaging system; vocal folds; wound healing