Impact of binding mode of low-sulfated hyaluronan to 3D collagen matrices on its osteoinductive effect for human bone marrow stromal cells

Abstract

Synthetically sulfated hyaluronan derivatives were shown to facilitate osteogenic differentiation of human bone marrow stromal cells (hBMSC) by application in solution or incorporated in thin collagen-based coatings. In the presented study, using a biomimetic three-dimensional (3D) cell culture model based on fibrillary collagen I (3D Col matrix), we asked on the impact of binding mode of low sulfated hyaluronan (sHA) in terms of adsorptive and covalent binding on osteogenic differentiation of hBMSC. Both binding modes of sHA induced osteogenic differentiation. Although for adsorptive binding of sHA a strong intracellular uptake of sHA was observed, implicating an intracellular mode of action, covalent binding of sHA to the 3D matrix induced also intense osteoinductive effects pointing towards an extracellular mode of action of sHA in osteogenic differentiation. In summary, the results emphasize the relevance of fibrillary 3D Col matrices as a model to study hBMSC differentiation in vitro in a physiological-like environment and that sHA can display dose-dependent osteoinductive effects in dependence on presentation mode in cell culture scaffolds.

Advances of Sulfonated Hyaluronic Acid in Biomaterials and Coatings—A Review

“…One of the main selective binding properties of S-HA is its high affinity for different cytokines and growth factors, including fibroblast growth factor (FBG), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β) [48]. These growth factors perform important roles in wound healing, tissue repair and angiogenesis, and S-HA capability to selectively bind to, and sequestering these factors can improve their bioactivity and support tissue regeneration [49].…”

A Self‐Assembled Matrix System for Cell‐Bioengineering Applications in Different Dimensions, Scales, and Geometries

“…The importance of GAG and proteoglycans for hMSC osteogenic differentiation has been investigated in several in vitro studies. [35][36][37][38][39][40][41][42] Synthetically S-HA as used in this study has been previously shown to promote the osteogenic differentiation of hMSC. [35,38,41] S-HA could alter several cellular processes such as cell signaling pathways (e.g., BMP-2 (bone morphogenetic protein-2) and TGF-β1 (transforming growth factor-β1) signaling), proteins involved in endocytosis, cell-ECM interaction, and ECM remodeling as well as matrix vesicle formation and composition.…”