Engineering RGD nanopatterned hydrogels to control preosteoblast behavior: A combined computational and experimental approach

• Published in: Biomaterials Vol. 28; no. 30; pp. 4409 - 4417
• Main Authors: Comisar, Wendy A, Kazmers, Nikolas H, Mooney, David J, Linderman, Jennifer J
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-10-2007
• Subjects: Advanced Basic Science; Alginates - chemistry; Animals; Bone tissue engineering; Cell Adhesion; Cell Differentiation; Cell Proliferation; Cells, Cultured; Computational Biology - methods; Dentistry; Extracellular Matrix - metabolism; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Hydrogel; Hydrogels; Ligands; Mice; Models, Biological; Nanopatterns; Nanotechnology; Oligopeptides - chemistry; Oligopeptides - metabolism; Oligopeptides - physiology; Osteoblasts - enzymology; Osteoblasts - physiology; Osteocalcin - secretion; Phosphorylation; RGD peptide; Tissue Engineering - methods; Nanopatterns; Bone tissue engineering; Hydrogel; RGD peptide; Cell adhesion
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2007.06.018

Abstract The adhesion ligand arginine–glycine–aspartic acid (RGD) has been coupled to various materials to be used as tissue culture matrices or cell transplantation vehicles, and recent studies indicate that nanopatterning RGD into high-density islands alters key cell behaviors. Previous studies have failed, however, to conclusively decouple the effects of RGD bulk density and individual pattern parameters (i.e. RGDs/island and island distribution) on these altered cell responses. Using a nanopatterned RGD-coupled alginate hydrogel matrix, this work combines computational, statistical and experimental approaches to elucidate the effects of RGD patterns on four key cell responses. This study shows that in MC3T3 preosteoblasts focal adhesion kinase (FAK) Y397 phosphorylation, cell spreading, and osteogenic differentiation can be controlled by RGD nanopatterning, with the distribution of islands throughout the hydrogel (i.e. how closely spaced the islands are) being the most significant pattern parameter. More closely spaced islands favor FAK Y397 phosphorylation and cell spreading, while more widely spaced islands favor differentiation. Proliferation, in contrast, is primarily a function of RGD bulk density. Nanopatterning of cell adhesion ligands has tremendous potential as a simple tool to gain significant control over multiple cell behaviors in engineered extracellular matrix (ECM).