A Soft Zwitterionic Hydrogel as Potential Coating on a Polyimide Surface to Reduce Foreign Body Reaction to Intraneural Electrodes

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-05, Vol.27 (10), p.3126
• Main Authors: Gori, Manuele, Giannitelli, Sara Maria, Vadalà, Gianluca, Papalia, Rocco, Zollo, Loredana, Sanchez, Massimo, Trombetta, Marcella, Rainer, Alberto, Di Pino, Giovanni, Denaro, Vincenzo
• Format: Article
• Language: English
• Subjects: Biocompatibility; Biomaterials; Biomedical materials; Cell viability; Coated electrodes; Coatings; Communication; Contact angle; Content analysis; Covalent bonds; Cytotoxicity; Diffusion rate; Drug delivery systems; Electrodes; Fibrosis; Fluorescence; Fluorescence microscopy; Foreign bodies; Fouling; Hydrogels; Inflammation; Inflammatory response; intraneural electrodes; Macrophages; Mechanical properties; Medical equipment; Modulus of elasticity; Oxidative stress; PEG; Physiology; Plasma; poly(SBMA); Polyethylene glycol; Polyimide; Polymers; Polystyrene resins; Prostheses; Prosthetics; Protective coatings; Stiffness; surface coating; Surgical implants; Thin films; Transplants & implants; zwitterionic hydrogel; Zwitterions
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27103126

Invasive intraneural electrodes can control advanced neural-interfaced prostheses in human amputees. Nevertheless, in chronic implants, the progressive formation of a fibrotic capsule can gradually isolate the electrode surface from the surrounding tissue leading to loss of functionality. This is due to a nonspecific inflammatory response called foreign-body reaction (FBR). The commonly used poly(ethylene glycol) (PEG)-based low-fouling coatings of implantable devices can be easily encapsulated and are susceptible to oxidative damage in long-term in vivo applications. Recently, sulfobetaine-based zwitterionic hydrogels have emerged as an important class of robust ultra-low fouling biomaterials, holding great potential to mitigate FBR. The aim of this proof-of-principle in vitro work was to assess whether the organic zwitterionic-poly(sulfobetaine methacrylate) [poly(SBMA)]-hydrogel could be a suitable coating for Polyimide (PI)-based intraneural electrodes to reduce FBR. We first synthesized and analyzed the hydrogel through a mechanical characterization (i.e., Young's modulus). Then, we demonstrated reduced adhesion and activation of fibrogenic and pro-inflammatory cells (i.e., human myofibroblasts and macrophages) on the hydrogel compared with PEG-coated and polystyrene surfaces using cell viability assays, confocal fluorescence microscopy and high-content analysis of oxidative stress production. Interestingly, we successfully coated PI surfaces with a thin film of the hydrogel through covalent bond and demonstrated its high hydrophilicity via water contact angle measurement. Importantly, we showed the long-term release of an anti-fibrotic drug (i.e., Everolimus) from the hydrogel. Because of the low stiffness, biocompatibility, high hydration and ultra-low fouling characteristics, our zwitterionic hydrogel could be envisioned as long-term diffusion-based delivery system for slow and controlled anti-inflammatory and anti-fibrotic drug release in vivo.