Bioactive surface coatings for nanoscale instruments: Effects on CNS neurons

Abstract

A method is described for depositing onto medical instruments highly biocompatible and bioactive surface coatings that can promote and stabilize cell attachment. The coatings were made by first depositing thin films of materials, such as diamond-like carbon, or metals, including tantalum, tungsten, platinum, gold, iridium, palladium, and brass. These surfaces were further altered to either promote or inhibit cell growth and spreading by an additional overcoat of biological materials, including the extracellular matrix proteins, laminin, fibronectin, and collagen IV. The deposition technique used a metal or carbon plasma, and the important properties of film adhesion, hardness, density, and smoothness are tailored by control of the ion bombardment energy. The films are translucent enough to permit high resolution light microscopy for rapid and detailed examination of tissue response. These bioactive substrates have been tested on primary central nervous system neurons, and the growth response is excellent. Equally successful have been our attempts to anchor neurons, without associated proliferation of non-neuronal cells, using coatings of poly-d-lysine. The method and the materials could have important ramifications in a number of areas of research and biotechnology, for example for chronic implantation of microelectrode arrays in the cerebral cortex for neuroprosthetic and neural monitoring application and for research on the human central nervous system. Possible application in nonneuronal fields, such as for coronary artery stents and pacemaker electrodes, also are discussed.

Materials considerations of implantable neuroengineering devices for clinical use

“…Other studies suggest a lesser role for these physical factors [27,33]. The latter are consistent with a recognition that the immune system is highly adept at recognizing any foreign object.…”

Response of brain tissue to chronically implanted neural electrodes

“…Although different materials were not tested by Szarowski et al, other experiments have not shown any significant reduction in the immune response with various metals (Ignatius et al, 1998) or other materials, such as DLC (Singh et al, 2003). Such studies support the shift from a materials science strategy in evading the immune response to strategies focusing on the molecular and cellular biology of the immune response.…”

“…Resins, such as Epoxylite, have also been used successfully (Liu et al, 1999). Plasma-deposited diamond-like carbon (DLC) has recently been demonstrated in vitro as both a chemically inert insulator and as a good substrate for biological molecule attachment to control the foreign body response, although it has not been tested in vivo (Ignatius et al, 1998;Singh et al, 2003).…”

“…Some of these cues are in the form of polypeptide motifs on extracellular matrix proteins or on membrane bound molecules of neighboring cells. In addition to intact cell adhesion proteins, such as collagen and fibronectin (Ignatius et al, 1998), several groups have employed cell adhesion peptides, such as RGD (Kam et al, 2002), found in many extracellular proteins, YIGSR (Kam et al, 2002;, and IKVAV (Kam et al, 2002), found in laminin and KHIFS-DDSSE (Kam et al, 2002), found on NCAM (neural-cell adhesion molecule). Studies to establish neuronal reactions to these proteins and peptides have been conducted in vitro.…”

Magnetic insertion system for flexible electrode implantation

“…The large mismatch between the modulus of silicon-based probes (∼172 GPa) (Weppelmann et al, 1993) and the brain (∼0.1 MPa) (Hirakawa et al, 1981) has been identified as a contributing factor in glial scar formation and subsequent long-term signal degradation (Lee et al, 2005;Subbaroyan et al, 2005). Efforts have been made to reduce scarring by developing coatings which improve neural cell attachment and growth (He and Bellamkonda, 2005;Ignatius et al, 1998) and prevent astrocyte adhesion (Singh et al, 2003). Such measures fail to address the severe mechanical mismatch between neural tissue and the probes themselves.…”