A tissue-specific, injectable acellular gel for the treatment of chronic vocal fold scarring

Che Xu, I-Fan T Mau

Research output: Contribution to journalArticle

Abstract

Gel-based injectable biomaterials have significant potential for treating vocal fold defects such as scarring. An ideal injectable for vocal fold lamina propria restoration should mimic the microenvironment of the lamina propria to induce scarless wound healing and functional tissue regeneration. Most current synthetic or natural injectable biomaterials do not possess the same level of complex, tissue-specific constituents as the natural vocal fold lamina propria. In this study we present a newly-developed injectable gel fabricated from decellularized bovine vocal fold lamina propria. Blyscan assay and mass spectrometry indicated that the vocal fold-specific gel contained a large amount of sulfated glycosaminoglycans and over 250 proteins. Gene Ontology overrepresentation analysis revealed that the proteins in the gel dominantly promote antifibrotic biological process. In vivo study using a rabbit vocal fold injury model showed that the injectable gel significantly reduced collagen density and decreased tissue contraction of the lamina propria in vocal folds with chronic scarring. Furthermore, this acellular gel only elicited minimal humoral immune response after injection. Our findings suggested that the tissue-specific, injectable extracellular matrix gel could be a promising biomaterial for treating vocal fold scarring, even after the formation of mature scar. Statement of Significance: Vocal fold lamina propria scarring remains among the foremost therapeutic challenges in the management of patients with voice disorders. Surgical excision of scar may cause secondary scarring and yield inconsistent results. The present study reports an extracellular matrix-derived biomaterial that demonstrated antifibrotic effect on chronic scarring in vocal fold lamina propria. Its injectability minimizes the invasiveness of the delivery procedure and the degree of mucosal violation. In this work we also describe a new methodology which can more accurately identify proteins from the complex mixture of an acellular extracellular matrix gel by excluding interfering peptides produced during the enzymatic digestion in gel fabrication.

Original languageEnglish (US)
JournalActa Biomaterialia
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Vocal Cords
Cicatrix
Gels
Tissue
Injections
Mucous Membrane
Biocompatible Materials
Biomaterials
Extracellular Matrix
Therapeutics
A73025
Proteins
Voice Disorders
Tissue regeneration
Biological Phenomena
Gene Ontology
Complex Mixtures
Collagen
Humoral Immunity
Peptides

Keywords

  • Fibrosis
  • Gene Ontology
  • Laryngeal regenerative medicine
  • Proteomics
  • Xenogeneic biomaterial

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

@article{d6fa7a895c404c6db22ce387283d5582,
title = "A tissue-specific, injectable acellular gel for the treatment of chronic vocal fold scarring",
abstract = "Gel-based injectable biomaterials have significant potential for treating vocal fold defects such as scarring. An ideal injectable for vocal fold lamina propria restoration should mimic the microenvironment of the lamina propria to induce scarless wound healing and functional tissue regeneration. Most current synthetic or natural injectable biomaterials do not possess the same level of complex, tissue-specific constituents as the natural vocal fold lamina propria. In this study we present a newly-developed injectable gel fabricated from decellularized bovine vocal fold lamina propria. Blyscan assay and mass spectrometry indicated that the vocal fold-specific gel contained a large amount of sulfated glycosaminoglycans and over 250 proteins. Gene Ontology overrepresentation analysis revealed that the proteins in the gel dominantly promote antifibrotic biological process. In vivo study using a rabbit vocal fold injury model showed that the injectable gel significantly reduced collagen density and decreased tissue contraction of the lamina propria in vocal folds with chronic scarring. Furthermore, this acellular gel only elicited minimal humoral immune response after injection. Our findings suggested that the tissue-specific, injectable extracellular matrix gel could be a promising biomaterial for treating vocal fold scarring, even after the formation of mature scar. Statement of Significance: Vocal fold lamina propria scarring remains among the foremost therapeutic challenges in the management of patients with voice disorders. Surgical excision of scar may cause secondary scarring and yield inconsistent results. The present study reports an extracellular matrix-derived biomaterial that demonstrated antifibrotic effect on chronic scarring in vocal fold lamina propria. Its injectability minimizes the invasiveness of the delivery procedure and the degree of mucosal violation. In this work we also describe a new methodology which can more accurately identify proteins from the complex mixture of an acellular extracellular matrix gel by excluding interfering peptides produced during the enzymatic digestion in gel fabrication.",
keywords = "Fibrosis, Gene Ontology, Laryngeal regenerative medicine, Proteomics, Xenogeneic biomaterial",
author = "Che Xu and Mau, {I-Fan T}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.actbio.2019.08.025",
language = "English (US)",
journal = "Acta Biomaterialia",
issn = "1742-7061",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - A tissue-specific, injectable acellular gel for the treatment of chronic vocal fold scarring

AU - Xu, Che

AU - Mau, I-Fan T

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Gel-based injectable biomaterials have significant potential for treating vocal fold defects such as scarring. An ideal injectable for vocal fold lamina propria restoration should mimic the microenvironment of the lamina propria to induce scarless wound healing and functional tissue regeneration. Most current synthetic or natural injectable biomaterials do not possess the same level of complex, tissue-specific constituents as the natural vocal fold lamina propria. In this study we present a newly-developed injectable gel fabricated from decellularized bovine vocal fold lamina propria. Blyscan assay and mass spectrometry indicated that the vocal fold-specific gel contained a large amount of sulfated glycosaminoglycans and over 250 proteins. Gene Ontology overrepresentation analysis revealed that the proteins in the gel dominantly promote antifibrotic biological process. In vivo study using a rabbit vocal fold injury model showed that the injectable gel significantly reduced collagen density and decreased tissue contraction of the lamina propria in vocal folds with chronic scarring. Furthermore, this acellular gel only elicited minimal humoral immune response after injection. Our findings suggested that the tissue-specific, injectable extracellular matrix gel could be a promising biomaterial for treating vocal fold scarring, even after the formation of mature scar. Statement of Significance: Vocal fold lamina propria scarring remains among the foremost therapeutic challenges in the management of patients with voice disorders. Surgical excision of scar may cause secondary scarring and yield inconsistent results. The present study reports an extracellular matrix-derived biomaterial that demonstrated antifibrotic effect on chronic scarring in vocal fold lamina propria. Its injectability minimizes the invasiveness of the delivery procedure and the degree of mucosal violation. In this work we also describe a new methodology which can more accurately identify proteins from the complex mixture of an acellular extracellular matrix gel by excluding interfering peptides produced during the enzymatic digestion in gel fabrication.

AB - Gel-based injectable biomaterials have significant potential for treating vocal fold defects such as scarring. An ideal injectable for vocal fold lamina propria restoration should mimic the microenvironment of the lamina propria to induce scarless wound healing and functional tissue regeneration. Most current synthetic or natural injectable biomaterials do not possess the same level of complex, tissue-specific constituents as the natural vocal fold lamina propria. In this study we present a newly-developed injectable gel fabricated from decellularized bovine vocal fold lamina propria. Blyscan assay and mass spectrometry indicated that the vocal fold-specific gel contained a large amount of sulfated glycosaminoglycans and over 250 proteins. Gene Ontology overrepresentation analysis revealed that the proteins in the gel dominantly promote antifibrotic biological process. In vivo study using a rabbit vocal fold injury model showed that the injectable gel significantly reduced collagen density and decreased tissue contraction of the lamina propria in vocal folds with chronic scarring. Furthermore, this acellular gel only elicited minimal humoral immune response after injection. Our findings suggested that the tissue-specific, injectable extracellular matrix gel could be a promising biomaterial for treating vocal fold scarring, even after the formation of mature scar. Statement of Significance: Vocal fold lamina propria scarring remains among the foremost therapeutic challenges in the management of patients with voice disorders. Surgical excision of scar may cause secondary scarring and yield inconsistent results. The present study reports an extracellular matrix-derived biomaterial that demonstrated antifibrotic effect on chronic scarring in vocal fold lamina propria. Its injectability minimizes the invasiveness of the delivery procedure and the degree of mucosal violation. In this work we also describe a new methodology which can more accurately identify proteins from the complex mixture of an acellular extracellular matrix gel by excluding interfering peptides produced during the enzymatic digestion in gel fabrication.

KW - Fibrosis

KW - Gene Ontology

KW - Laryngeal regenerative medicine

KW - Proteomics

KW - Xenogeneic biomaterial

UR - http://www.scopus.com/inward/record.url?scp=85072025022&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072025022&partnerID=8YFLogxK

U2 - 10.1016/j.actbio.2019.08.025

DO - 10.1016/j.actbio.2019.08.025

M3 - Article

C2 - 31425889

AN - SCOPUS:85072025022

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

ER -