Alginate type and RGD density control myoblast phenotype.
Alginates are being increasingly used for cell encapsulation and tissue engineering applications; however, these materials cannot specifically interact with mammalian cells. We have covalently modified alginates of varying monomeric ratio with RGD-containing cell adhesion ligands using carbodiimide chemistry to initiate cell adhesion to these polymers. We hypothesized that we could control the function of cells adherent to RGD-modified alginate hydrogels by varying alginate polymer type and cell adhesion ligand density, and we have addressed this possibility by studying the proliferation and differentiation of C2C12 skeletal myoblasts adherent to these materials. RGD density on alginates of varying monomeric ratio could be controlled over several orders of magnitude, creating a range of surface densities from 1-100 fmol/cm(2). Myoblast adhesion to these materials was specific to the RGD ligand, because adhesion could be competed away with soluble RGD in a dose-dependent manner. Myoblast proliferation and differentiation could be regulated by varying the alginate monomeric ratio and the density of RGD ligands at the substrate surface, and specific combinations of alginate type and RGD density were required to obtain efficient myoblast differentiation on these materials.
Rowley
Jon A
JA
Department of Biomedical Engineering, University of Michigan, Colleges of Engineering and Dentistry, Ann Arbor, Michigan, USA.
Mooney
David J
DJ
D000464:Alginates / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002459:Cell Fusion; D002460:Cell Line; D005109:Extracellular Matrix / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020100:Hydrogels; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008024:Ligands; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010641:Phenotype
D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D007457:Iodine Radioisotopes; D008024:Ligands; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; C008324:mannuronic acid