Cell Attachment and Motility on Materials Modified by Surface‐active RGD‐containing Peptides

The development of materials for use in the fabrication of implantable medical devices was initially based on the concept of using materials that were refractile to cell interaction. It has become increasingly clear, however, that the relatively inert nature of materials seen in vitro does not translate to devices implanted for long periods of time. In addition, material surfaces can elicit varying types of cell responses, some resulting in adverse resctions. This has prompted an effort to create or modify materials in ways that promote controlled cell response at the material surface.' One such strategy for creating a cell interactive surface of a biomaterial involves the use of adsorbed extracellular matrix proteins (ECM) to provide specific signals for cell attachment.2 This method has been refined by the use of short synthetic peptides containing the cell-binding domains of ECM proteins6 One sequence that functions well as a cell-binding site is the tripeptide ArgGly-Asp (RGD), originally isolated as the cell-binding domain of fibronectin.' The RGD sequence has been identified as a cell-binding domain in a number of other ECM proteins, each of which is recognized by distinct cell-surface receptors, termed in tegr in~ .~ ' The observation that cell attachment can be directed to surfaces modified with small synthetic RGD-containing peptides has provided the incentive to modify and fabricate the sequence into biomaterials. A number of investigators have created cell attachment-competent surfaces by covalently coupling RGD peptides to materials, such as glycophase glass,s polyacrylamide? ethylene-acrylic acid copolymer,I0 polyethylene terephthalate," polytetrafluoroethylene,'2 and polyvinyl alcohol. The RGD sequence has also been used to modify the base monomer of polyurethane and thus form a material having sites for cell attachment throughout the material.I4 The use of covalent methods to immobilize the bioactive species is somewhat limited due to the constraints imposed by the material surface chemistry as well as the difficulties associated with modifying complex prefabricated medical devices. An alternative approach to modify the surface of a material involves the use of adsorptive interactions to bind molecules to the surface. This has proved successful for the immobilization of block copolymers that act to inhibit protein adsorption to blood-contacting biomaterial~.'~ We used a similar strategy to create RGD-containing peptides having a stretch of hydrophobic amino acids that mediate the interaction