Modulation of chondrocyte phenotype for tissue engineering by designing the biologic-polymer carrier interface.
Therapeutic strategies based on cell and tissue engineering can be advanced by developing material substrates that effectively interrogate the biological compartment, with or without the complimentary local release of growth factors. Poly(ether ester) segmented copolymers were engineered as model material systems to elucidate the interfacial molecular events that govern the function of adhered cells. Surface chemistry was modulated by varying poly(ethylene glycol) (PEG) length and mole fraction with poly(butylene terephthalate) (PBT), leading to differential competitive protein adsorption of fibronectin and vitronectin from serum and consequently to different cell attachment modes. Adhesion within the hydrogel-like milieu of longer surface PEG was mediated via binding to the CD44 transmembrane receptor, rather than the RGD-integrin mechanism, whereas greater substrate-bound fibronectin resulted in cell adhesion via integrins. These adhesion modalities differentially impacted morphological cell phenotype (spread or spheroid) and the subsequent expression of mRNA transcripts (collagen types II, I) characteristic of phenotypically differentiated or dedifferentiated chondrocytes, respectively. These results demonstrate that materials can be designed to directly elicit the membrane bound receptor apparatus desired for downstream cellular response, without requiring exogenous biological growth factors to enable differentiated potential.
Mahmood
Tahir A
TA
Institute of Biomedical Technology, University of Twente, Prof. Bronkhorstlaan 10, 3723 MB Bilthoven, The Netherlands. tmahmood@amgen.com
Miot
Sylvie
S
Frank
Oliver
O
Martin
Ivan
I
Riesle
Jens
J
Langer
Robert
R
van Blitterswijk
Clemens A
CA
D015153:Blotting, Western; D002448:Cell Adhesion; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D003094:Collagen / Q000235:genetics; D008855:Microscopy, Electron, Scanning; D010641:Phenotype; D011092:Polyethylene Glycols / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011108:Polymers / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics; D023822:Tissue Engineering
D011108:Polymers; D012333:RNA, Messenger; D011092:Polyethylene Glycols; D003094:Collagen