title: Type, density, and presentation of grafted adhesion peptides on polysaccharide-based hydrogels control preosteoblast behavior and differentiation.
abstract: In this work, cell-responsive polysaccharide hydrogels were prepared by a simple procedure based on the sequential bioconjugation and cross-linking of the polysaccharide backbone with bioactive peptides and poly(ethylene glycol)-bis(thiol) (PEG-(SH)2), respectively. Using thiol-ene reactions, we successfully functionalized hyaluronic acid (HA) and carboxymethylcellulose (CMC) with short and long peptides (5-mer and 15-mer derivatives, respectively) derived from adhesive proteins of bone extracellular matrix. The resulting HA-peptide and CMC-peptide conjugates with varying degrees of substitution were then carefully characterized by (1)H NMR spectroscopy to precisely control the peptide density into the hydrogels cross-linked with PEG-(SH)2. Preosteoblast seeded on the hydrogels with controlled identical stiffness spread in a manner that was strongly dependent on ligand density. Surprisingly, increasing the density of the adhesive peptide anchors did not result in a plateau of initial cell spreading but rather in a bell-shaped cell response that varies with the nature of both polysaccharide backbone and functional peptide. Placing the cells under optimal conditions for cell/hydrogel interaction, we showed that in HA hydrogels, the polysaccharide moiety is not solely a passive scaffold that presents the active peptides but is an active player in cell microenvironment to control and sustain cell activity.
authors: University Grenoble Alpes, CERMAV , 601 Rue de la Chimie, F-38000 Grenoble, France.
authors: Jing
authors: J
authors: Jing
authors: Audrey
authors: A
authors: Fournier
authors: Anna
authors: A
authors: Szarpak-Jankowska
authors: Marc R
authors: MR
authors: Block
authors: Rachel
authors: R
authors: Auzély-Velty
mesh_terms: D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003470:Culture Media; D005353:Fibronectins / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels; D058574:Integrin-Binding Sialoprotein / Q000737:chemistry*; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D010012:Osteogenesis; D010446:Peptide Fragments / Q000737:chemistry
chemical_list: D003470:Culture Media; D005353:Fibronectins; D020100:Hydrogels; D058574:Integrin-Binding Sialoprotein; D010446:Peptide Fragments; D006820:Hyaluronic Acid; D002266:Carboxymethylcellulose Sodium