Modulation of Chondrocyte Phenotype for Tissue Engineering by Designing the Biologic−Polymer Carrier Interface

Abstract

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 hydrogellike 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.

Application of MS-Based Proteomics to Study Serum Protein Adsorption/Absorption and Complement C3 Activation on Poly(ethylene glycol) Hydrogels

“…Furthermore, no vitronectin or thrombin was detected on PEG hydrogels in either fractionated or whole serum, suggesting the adsorption of vitronectin and thrombin was inhibited by PEG hydrogels. PEG was observed to decrease the vitronectin adsorption to PEG-terephthalate and poly(butylene terephthalate) co-polymers [22]. The modification to polydimethylsiloxane with allyl-PEG-methoxy also reduced the generation of thrombin and the adsorption of fibrinogen [23].…”

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

“…PEOT/PBT 2D films with a higher PEOT mass ratio were found to support a rounded chondrocyte morphology, no proliferation, and higher collagen II:collagen I gene expression; films with a higher PBT mass ratio supported a flat cell morphology, cell adhesion, and proliferation (121, 122). Similarly, chondrocytes cultured in 3D scaffolds with the composition 1000PEG-70:30 (PEG molecular weight = 1000 g/mol; 70% PEOT and 30% PBT by mass) secreted more sulfated glycosaminoglycans (GAGs) than those in 300PEG-55:45 scaffolds after 4 weeks of in vitro culture (117).…”

Surface strategies for control of neuronal cell adhesion: A review

“…Combinations of cell adhesive and repellent chemistries are often used to guide cell adhesion and process outgrowth. Interestingly one of the most used surfaces to prevent protein and cell binding is the hydrophilic polymer polyethylene glycol (PEG) [72,73]. PEG is commonly used to suppress protein adsorption and subsequently cell attachment.…”