Zwitterionic Polymer Coating Suppresses Microglial Encapsulation to Neural Implants In Vitro and In Vivo

Abstract

For brain computer interfaces (BCI), the immune response to implanted electrodes is a major biological cause of device failure. Bioactive coatings such as neural adhesion molecule L1 have been shown to improve the biocompatibility, but are difficult to handle or produce in batches. Here, a synthetic zwitterionic polymer coating, poly(sulfobetaine methacrylate) (PSBMA) is developed for neural implants with the goal of reducing the inflammatory host response. In tests in vitro, the zwitterionic coating inhibits protein adsorption and the attachment of fibroblasts and microglia, and remains stable for at least 4 weeks. In vivo two‐photon microscopy on CX3CR1‐GFP mice shows that the zwitterionic coating significantly suppresses the microglial encapsulation of neural microelectrodes over a 6 h observation period. Furthermore, the lower microglial encapsulation on zwitterionic polymer‐coated microelectrodes is revealed to originate from a reduction in the size but not the number of microglial end feet. This work provides a facile method for coating neural implants with zwitterionic polymers and illustrates the initial interaction between microglia and coated surface at high temporal and spatial resolution.

Immobilization of Nanobodies with Vapor-Deposited Polymer Encapsulation for Robust Biosensors

“…Surface-immobilized proteins, antibodies, and other similar biomolecules form the basis of most known biosensors, biomolecular electronics, and nanodevices. − Although a number of surface immobilization chemistries are reported, comparatively fewer strategies for maintaining the function and stability of these surface-immobilized biomolecules, especially upon long-term storage, are known . Particularly for biosensors, it is imperative to maintain constant reaction conditions and to suppress nonspecific binding interactions that could lead to decreased target diffusion to the sensing interface and result in significant signal loss. , Careless choice of surface treatments can damage biomolecules involved in the sensing process and, eventually, significantly shorten the shelf-life and accuracy of the biosensors over time.…”

“…Layer-by-layer assemblies , and in situ polymerized coatings , also serve as encapsulants for intact biosensing systems. However, the non-conformal nature of these solution-processed coatings often hinders analyte diffusion to the underlying sensing element, which leads to inaccurate signal acquisition and increases signal integration times.…”

Cellular Interactions with Lubricin and Hyaluronic Acid–Lubricin Composite Coatings on Gold Electrodes in Passive and Electrically Stimulated Environments

“…One of the strategies for combatting device fouling and fibrosis involves the application of antifouling coatings. Traditional and widely used antifouling coatings, such as poly­(ethylene glycol) or zwitterionic coatings − although highly effective in many applications, have demonstrated poor efficacy in bionic devices due to electrical passivation of electrode surface efficiency ,, and limited ability to inhibit cell attachment . Likewise, surface grafting of antiadhesive agents utilizing linker/cross-linker chemistries and grafting-from polymerization reactions , typically requires multiple fabrication steps , and long fabrication times , and can lead to nonuniform coatings when applied to micro/nanostructured electrodes due to variable reaction kinetics arising from a complicated geometry.…”

Immobilization of Nanobodies with Vapor-Deposited Polymer Encapsulation for Robust Biosensors

“…[1][2][3][4][5] Although a number of surface immobilization chemistries are reported, comparatively fewer strategies for maintaining the function and stability of these surfaceimmobilized biomolecules, especially upon long-term storage, are known. 6 Particularly for biosensors, it is imperative to maintain constant reaction conditions and to suppress nonspecific binding interactions that could lead to decreased target diffusion to the sensing interface and result in significant signal loss. [7][8] Careless choice of surface treatments can damage biomolecules involved in the sensing process and, eventually, significantly shorten the shelf-life and accuracy of the biosensors over time.…”

“…15 An emerging encapsulation strategy is to coat surfaces with polymers that present low surface energies, such as hyperbranched fluoropolymers, polypeptides, or silicone elastomers, and, thus, facilitate removal of adsorbed biomacromolecules by a limited shear force, like gentle rinsing. [16][17] Layer-by-layer assemblies [18][19] and in situ polymerized coatings 6,20 also serve as encapsulants for intact biosensing systems. However, the non-conformal nature of these solution-processed coatings often hinders analyte diffusion to the underlying sensing element, which leads to inaccurate signal acquisition and increases signal integration times.…”