Investigation of the Viability, Adhesion, and Migration of Human Fibroblasts in a Hyaluronic Acid/Gelatin Microgel-Reinforced Composite Hydrogel for Vocal Fold Tissue Regeneration

Adv Healthc Mater. 2016 Jan 21;5(2):255-65. doi: 10.1002/adhm.201500370. Epub 2015 Oct 26.

Abstract

The potential use of a novel scaffold biomaterial consisting of cross-linked hyaluronic acid (HA)-gelatin (Ge) composite microgels is investigated for use in treating vocal fold injury and scarring. Cell adhesion integrins and kinematics of cell motion are investigated in 2D and 3D culture conditions, respectively. Human vocal fold fibroblast (hVFF) cells are seeded on HA-Ge microgels attached to a HA hydrogel thin film. The results show that hVFF cells establish effective adhesion to HA-Ge microgels through the ubiquitous expression of β1 integrin in the cell membrane. The microgels are then encapsulated in a 3D HA hydrogel for the study of cell migration. The cells within the HA-Ge microgel-reinforced composite hydrogel (MRCH) scaffold have an average motility speed of 0.24 ± 0.08 μm min(-1) . The recorded microscopic images reveal features that are presumably associated with lobopodial and lamellipodial cell migration modes within the MRCH scaffold. Average cell speed during lobopodial migration is greater than that during lamellipodial migration. The cells move faster in the MRCH than in the HA-Ge gel without microgels. These findings support the hypothesis that HA-Ge MRCH promotes cell adhesion and migration; thereby they constitute a promising biomaterial for vocal fold repair.

Keywords: cell adhesion/spreading; cell migration mechanisms; hyaluronic acid/gelatin hydrogel; vocal fold repair.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism
  • Cell Adhesion / drug effects
  • Cell Death / drug effects
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects
  • Gelatin / pharmacology*
  • Humans
  • Hyaluronic Acid / pharmacology*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology*
  • Polyethylene Glycols / chemistry
  • Regeneration / drug effects*
  • Sulfhydryl Compounds / metabolism
  • Tissue Scaffolds / chemistry
  • Vocal Cords / cytology
  • Vocal Cords / drug effects
  • Vocal Cords / physiology*

Substances

  • Actins
  • Sulfhydryl Compounds
  • poly(ethylene glycol)diacrylate
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Polyethylene Glycols
  • Gelatin
  • Hyaluronic Acid