Peptide modification of polyimide-insulated microwires: Towards improved biocompatibility through reduced glial scarring.

The goal of this study is to improve the integration of implanted microdevices with tissue in the central nervous system (CNS). The long-term utility of neuroprosthetic devices implanted in the CNS is affected by the formation of a scar by resident glial cells (astrocytes and microglia), limiting the viability and functional stability of the devices. Reduction in the proliferation of glial cells is expected to enhance the biocompatibility of devices. We demonstrate the modification of polyimide-insulated microelectrodes with a bioactive peptide KHIFSDDSSE. Microelectrode wires were functionalized with (3-aminopropyl) triethoxy silane (APTES); the peptide was then covalently bonded to the APTES. The soluble peptide was tested in 2D mixed cultures of astrocytes and microglia, and reduced the proliferation of both cell types. The interactions of glial cells with the peptide-modified wires was then examined in 3D cell-laden hydrogels by immunofluorescence microscopy. As expected for uncoated wires, the microglia were first attracted to the wire (7days) followed by astrocyte recruitment and hypertrophy (14days). For the peptide-treated wires, astrocytes coated the wires directly (24h), and formed a thin, stable coating without evidence of hypertrophy, and the attraction of microglia to the wire was significantly reduced. The results suggest a mechanism to improve tissue integration by promoting uniform coating of astrocytes on a foreign body while lessening the reactive response of microglia. We conclude that the bioactive peptide KHIFSDDSSE may be effective in improving the biocompatibility of neural interfaces by both reducing acute glial reactivity and generating stable integration with tissue.

STATEMENT OF SIGNIFICANCE: The peptide KHIFSDDSSE has previously been shown in vitro to both reduce the proliferation of astrocytes, and to increase the adhesion of astrocyte to glass substrates. Here, we demonstrate a method to apply uniform coatings of peptides to microwires, which could readily be generalized to other peptides and surfaces. We then show that when peptide-modified wires are inserted into 3D cell-laden hydrogels, the normal cellular reaction (microglial activation followed by astrocyte recruitment and hypertrophy) does not occur, rather astrocytes are attracted directly to the surface of the wire, forming a relatively thin and uniform coating. This suggests a method to improve tissue integration of implanted devices to reduce glial scarring and ultimately reduce failure of neural interfaces.