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

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 (gamma-glutamic acid) (gamma-PGA) hydrogels with robust mechanical properties were developed based on methacrylate-gamma-PGA (gamma-PGA-GMA) and cysteamine functionalized gamma-PGA (gamma-PGA-SH) for cartilage regeneration. The gamma-PGA hydrogels demonstrated good self-crosslinking property as well as tunability through conjugation between active thiol groups of gamma-PGA-SH and methacrylate moieties of gamma-PGA-GMA. The mechanical property, porous structure, swelling, and degradation process of the hydrogels could be controlled by adjusting modified gamma-PGA polymers component. The rheological behavior and compression test of gamma-PGA hydrogels illustrated a wide processing range in addition to superb mechanical properties. These gamma-PGA hydrogels showed excellent elasticity as well as toughness, withstanding more than 70% of mechanical strain. Meanwhile, the stress modulus of gamma-PGA hydrogels could be up to 749 kPa. We also studied gamma-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 gamma-PGA-based hydrogels hold promising application as favorable scaffold biomaterials for cartilage tissue regeneration. (C) 2019 Elsevier B.V. All rights reserved.