title: The Synergistic Effects of Matrix Stiffness and Composition on the Response of Chondroprogenitor Cells in a 3D Precondensation Microenvironment.
abstract: Improve functional quality of cartilage tissue engineered from stem cells requires a better understanding of the functional evolution of native cartilage tissue. Therefore, a biosynthetic hydrogel was developed containing RGD, hyaluronic acid and/or type-I collagen conjugated to poly(ethylene glycol) acrylate to recapitulate the precondensation microenvironment of the developing limb. Conjugation of any combination of the three ligands did not alter the shear moduli or diffusion properties of the PEG hydrogels; thus, the influence of ligand composition on chondrogenesis could be investigated in the context of varying matrix stiffness. Gene expression of ligand receptors (CD44 and the b1-integrin) as well as markers of condensation (cell clustering and N-cadherin gene expression) and chondrogenesis (Col2a1 gene expression and sGAG production) by chondroprogenitor cells in this system were modulated by both matrix stiffness and ligand composition, with the highest gene expression occurring in softer hydrogels containing all three ligands. Cell proliferation in these 3D matrices for 7 d prior to chondrogenic induction increased the rate of sGAG production in a stiffness-dependent manner. This biosynthetic hydrogel supports the features of early limb-bud condensation and chondrogenesis and is a novel platform in which the influence of the matrix physicochemical properties on these processes can be elucidated.
authors.affiliation: Biomedical Engineering, University of Michigan, Ann Arbor, 48109, USA.
authors.forename: Bita
authors.initials: B
authors.lastname: Carrion
authors.affiliation: Biomedical Engineering, University of Michigan, Ann Arbor, 48109, USA.
authors.forename: Mohammad F
authors.initials: MF
authors.lastname: Souzanchi
authors.affiliation: Chemistry, University of Michigan, Ann Arbor, 48109, USA.
authors.forename: Victor T
authors.initials: VT
authors.lastname: Wang
authors.affiliation: Biomedical Engineering, University of Michigan, Ann Arbor, 48109, USA.
authors.forename: Gopinath
authors.initials: G
authors.lastname: Tiruchinapally
authors.affiliation: Biomedical Engineering, University of Michigan, Ann Arbor, 48109, USA.
authors.forename: Ariella
authors.initials: A
authors.lastname: Shikanov
authors.affiliation: Biomedical Engineering, University of Michigan, Ann Arbor, 48109, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Putnam
authors.affiliation: Biomedical Engineering, University of Michigan, Ann Arbor, 48109, USA.|Mechanical Engineering, University of Michigan, Ann Arbor, 48109, USA.
authors.forename: Rhima M
authors.initials: RM
authors.lastname: Coleman
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002356:Cartilage; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D024042:Collagen Type I / Q000008:administration & dosage* / Q000737:chemistry; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry; D020100:Hydrogels / Q000008:administration & dosage*; D008024:Ligands; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: C497483:CD44 protein, human; D015820:Cadherins; D024042:Collagen Type I; D018960:Hyaluronan Receptors; D020100:Hydrogels; D008024:Ligands; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid
keywords: 3D; chondrogenesis; condensation; engineered microenvironment; matrix stiffness; polyethylene glycol