Osteogenic Cell Attachment to Degradable Polymers

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OSTEOGENIC CELL ATTACHMENT TO DEGRADABLE POLYMERS tKevin E. Healy, Davis Tsai,* and Jung E. Kim" "tDepts.of Biological Materials and Biomedical Engineering, Northwestern University, Chicago, IL. *School of Medicine, Northwestern University, Chicago, IL. 'Dept. of Materials Science and Engineering, Northwestern University, Evanston, IL.

Abstract Modifications were made to increase osteogenic cell adhesion to homo and copolymers of lactic and glycolic acid. A synthetic peptide containing the cell attachment signal Arginine-Glycine-Aspartate (RGD) was loaded into the polymers or adsorbed to the polymers' surfaces. Cell attachment was assayed after 24 hours incubation with an osteogenic cell line (ROS 17/2.8). Statistically significant differences in cell adhesion occurred between the polymers with the adsorbed peptides and the other treatment groups. Significant differences were not observed for the peptide loaded polymers and controls. These data indicate that precoating the polymer surface with a RGD-containing peptide prior to exposure to osteogenic cells increased cell attachment. For the current materials tested, the surface modification is preferred to increase osteogenic cell adhesion to degradable polyesters.

Introduction A critical need exists to develop materials that aid in the regeneration of bone tissue. An attractive method to achieve this goal is to culture host cells on scaffolds made of degradable polyesters in vitro and to subsequently implant this bio/artificial material, during which time the artificial material degrades and leaves the native tissue to function naturally. Any effort to regenerate bone must consider the biological activity of the scaffold and surrounding milieu. In the body, the extracellular matrix (ECM) influences development, polarity and behavior of anchorage-dependent cells. Control is due to the interaction between cell surface receptors and cell binding domains on extracellular adhesion proteins, such as fibronectin, vitronectin and the collagens. During cell-substrate adhesion a family of structurally related receptors called integrins recognizes the shared cell binding domain Arginine-Glycine-Aspartate (RGD) on fibronectin, laminin, vitronectin, and type I collagen [1],[2]. The RGD domain has also been identified in osteogenic cell-substrate adhesion [31,[4]. Cell attachment has been duplicated by using a small synthetic peptide containing the RGD amino acid sequence [5],[6]. For extracellular solutions containing concentrations of RGDcontaining peptides in the mM range, inhibition of cell attachment has been observed [5]. Small synthetic peptides containing the RGD cell binding sequence are excellent choices for therapeutic applications because the native proteins can undergo proteolysis and denaturation. Degradable polyesters can be used to fabricate the scaffolds and serve as the Mat. Res. Soc. Symp. Proc. Vol. 252. c 1992 Materials Research Society

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building blocks to create an artificial ECM. Homo and copolymers of poly lactic acid and poly glycolic acid are at