TGF-β1-Modified Hyaluronic Acid/Poly(glycidol) Hydrogels for Chondrogenic Differentiation of Human Mesenchymal Stromal Cells

Macromol Biosci. 2018 Jul;18(7):e1700390. doi: 10.1002/mabi.201700390. Epub 2018 May 21.

Abstract

In cartilage regeneration, the biomimetic functionalization of hydrogels with growth factors is a promising approach to improve the in vivo performance and furthermore the clinical potential of these materials. In order to achieve this without compromising network properties, multifunctional linear poly(glycidol) acrylate (PG-Acr) is synthesized and utilized as crosslinker for hydrogel formation with thiol-functionalized hyaluronic acid via Michael-type addition. As proof-of-principle for a bioactivation, transforming growth factor-beta 1 (TGF-β1) is covalently bound to PG-Acr via Traut's reagent which does not compromise the hydrogel gelation and swelling behavior. Human mesenchymal stromal cells (MSCs) embedded within these bioactive hydrogels show a distinct dose-dependent chondrogenesis. Covalent incorporation of TGF-β1 significantly enhances the chondrogenic differentiation of MSCs compared to hydrogels with supplemented noncovalently bound TGF-β1. The observed chondrogenic response is similar to standard cell culture with TGF-β1 addition with each medium change. In general, multifunctional PG-Acr offers the opportunity to introduce a range of biomimetic modifications (peptides, growth factors) into hydrogels and, thus, appears as an attractive potential material for various applications in regenerative medicine.

Keywords: TGF-β1; chondrogenesis; hyaluronic acid; mesenchymal stromal cells; poly(glycidol).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylates / chemistry
  • Cell Differentiation / drug effects*
  • Cells, Immobilized / cytology
  • Cells, Immobilized / drug effects
  • Cells, Immobilized / metabolism
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Chondrogenesis / drug effects
  • Glycoconjugates / chemistry
  • Humans
  • Hyaluronic Acid / chemistry*
  • Hydrogels / chemistry*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Primary Cell Culture
  • Propylene Glycols / chemistry*
  • Protein Binding
  • Tissue Engineering / methods
  • Tissue Scaffolds
  • Transforming Growth Factor beta1 / chemistry
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • Acrylates
  • Glycoconjugates
  • Hydrogels
  • Propylene Glycols
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • polyglycidol
  • Hyaluronic Acid