The Synergistic Effects of Matrix Stiffness and Composition on the Response of Chondroprogenitor Cells in a 3D Precondensation Microenvironment.
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.
['Carrion|Bita|B|', 'Souzanchi|Mohammad F|MF|', 'Wang|Victor T|VT|', 'Tiruchinapally|Gopinath|G|', 'Shikanov|Ariella|A|', 'Putnam|Andrew J|AJ|', 'Coleman|Rhima M|RM|']
D000818:Animals D015820:Cadherins D002356:Cartilage D002460:Cell Line D049109:Cell Proliferation D002478:Cells, Cultured D020219:Chondrogenesis D024042:Collagen Type I D005109:Extracellular Matrix D015870:Gene Expression D018960:Hyaluronan Receptors D006820:Hyaluronic Acid D020100:Hydrogels D008024:Ligands D051379:Mice D011092:Polyethylene Glycols D013234:Stem Cells D023822:Tissue Engineering D054457:Tissue Scaffolds
matrix stiffness 3D chondrogenesis condensation engineered microenvironment polyethylene glycol