Bioinspired poly (γ-glutamic acid) hydrogels for enhanced chondrogenesis of bone marrow-derived mesenchymal stem cells

Int J Biol Macromol. 2020 Jan 1:142:332-344. doi: 10.1016/j.ijbiomac.2019.09.104. Epub 2019 Oct 5.

Abstract

While peptide-directed scaffolds now serve as well-established platforms for biomimetic three-dimensional (3D) extracellular matrices (ECM), challenges still remain for chondrogenesis through direct mediation of stem cells. Here, biocompatible poly (γ-glutamic acid) (γ-PGA) hydrogels with robust mechanical properties were developed based on methacrylate-γ-PGA (γ-PGA-GMA) and cysteamine functionalized γ-PGA (γ-PGA-SH) for cartilage regeneration. The γ-PGA hydrogels demonstrated good self-crosslinking property as well as tunability through conjugation between active thiol groups of γ-PGA-SH and methacrylate moieties of γ-PGA-GMA. The mechanical property, porous structure, swelling, and degradation process of the hydrogels could be controlled by adjusting modified γ-PGA polymers component. The rheological behavior and compression test of γ-PGA hydrogels illustrated a wide processing range in addition to superb mechanical properties. These γ-PGA hydrogels showed excellent elasticity as well as toughness, withstanding more than 70% of mechanical strain. Meanwhile, the stress modulus of γ-PGA hydrogels could be up to 749 kPa. We also studied γ-PGA hydrogels as scaffolds for the 3D culture and chondrogenesis differentiation of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. In a rabbit auricular cartilage defect model, BMSCs-laden hydrogel effectively promoted chondrogenesis. Based on these findings, biomimetic γ-PGA-based hydrogels hold promising application as favorable scaffold biomaterials for cartilage tissue regeneration.

Keywords: Bionic extracellular matrix; Bone marrow-derived mesenchymal stem cells; Cartilage repair; Poly (γ-glutamic acid) hydrogel scaffold.

MeSH terms

  • Animals
  • Cartilage / cytology
  • Cell Differentiation
  • Cell Survival
  • Cells, Cultured
  • Chondrogenesis*
  • Extracellular Matrix
  • Hydrogels / chemistry*
  • Immunohistochemistry
  • Mechanical Phenomena
  • Mesenchymal Stem Cells / cytology*
  • Molecular Structure
  • Polyglutamic Acid / analogs & derivatives*
  • Polyglutamic Acid / chemistry
  • Polymers
  • Rabbits
  • Rheology
  • Tissue Scaffolds / chemistry

Substances

  • Hydrogels
  • Polymers
  • poly(gamma-glutamic acid)
  • Polyglutamic Acid