Background:

Surfaces have been extensively modified by chemical, biochemical, and topographic means to render them either adhesive or resistant to cells, and the resulting knowledge base has had a very substantial impact both on the basic scientific understanding of cell-material interactions as well as on important applications associated with biomedical devices and tissue-engineering constructs. Because of the many varied specific and non-specific mechanisms involved in cell adhesion, however, a surface that is adhesive to one cell type is usually also adhesive, to varying degrees, to other cell types. The surfaces of orthopedic implants are no exception. The oxidized metal or hydroxyapatite-coated surfaces used in most implant applications satisfy the critical design criteria of being osteoinductive, but they are also adhesive to bacteria. Several materials modifications have been made to render such surfaces resistant to bacteria—PEGylation, for example, has been used—but these bacteria-resistant surfaces also resist adhesion of eukaryotic cells.

Surface coatings having submicron features offer a solution to the problem of creating a surface that is differentially adhesive to osteoblasts and bacteria. This solution is based on the modulation of surface adhesiveness using nanoscale hetero-features organized on surfaces in two dimensions at submicron length scales. Such patterning is being explored in several contexts, including control of cell adhesiveness. However, the idea of modulating nanoscale adhesiveness to achieve differential cell adhesion based on fundamental differences in the length-scale properties of bacteria and eukaryotic cells is new.

Summary:

This invention provides a new surface treatment that permits the adhesion of one or more types of eukaryotic cells on a surface while simultaneously resisting adhesion by one or more types of non-eukaryotic cells (e.g., bacteria). This differential adhesiveness has applicability toward reducing the risk of infection associated with articles to be implanted in living bodies. In one embodiment, the invention provides a surface coating that is differentially adhesive to bacteria and eukaryotic cells, and comprises a primer coat that permits eukaryotic cells to adhere thereto, and a plurality of macromolecular structures, such as nanohydrogels, attached to the primer coat. At least some of the macromolecular structures are cell-resistant (i.e., they resist the adhesion of cells thereto), and are sufficiently distributed across an area of the primer coat so as to permit the adhesion of eukaryotic cells thereto and repel bacteria therefrom. The primer coat of the surface coating described above, is provided with a factor to promote the adhesion of eukaryotic cells to the primer coat. In yet another embodiment, the surface coating is provided with both cell-resistant macromolecular structures and macromolecular structures that include a factor to promote the adhesion of eukaryotic cells thereto. The primer coat comprises a self-assembled monolayer of polymer formed by electrostatic self-assembly of the monolayer on a substrate, and the macromolecular structures are deposited on the primer coat by electrostatic self-assembly on the monolayer. An article is provided having the surface coating assembled upon it, and, in a variation of the yet further embodiment, the surface coating is self-assembled on a continuous, topographically complex surface of the article.

Benefits:

- Surface coatings, particularly those having cell-resistant properties.

Application:

- Potential usage in medical field, especially orthopedic implants.

Full Patent: Surfaces Differentially Adhesive To Bacteria And Eukaryotic Cells