Introduction Invasive intraneural electrodes can control advanced neural-interfaced prostheses in human amputees [1]. Nevertheless, in chronic implants the gradual loss of functionality due to the progressive formation of a fibrotic capsule can ultimately isolate the electrode surface from the surrounding tissue. This is due to a nonspecific inflammatory response called foreign-body reaction (FBR) [2,3]. Poly(ethylene glycol) (PEG) is one of the most widely used low-fouling coatings of implantable devices. However, PEG can be easily encapsulated and susceptible to oxidative damage in long-term in vivo applications [4]. Recently, sulfobetaine-based zwitterionic hydrogels have emerged as an important class of robust ultra- low fouling biomaterials that ameliorate the performance of metal electrodes, holding great potential to reduce the FBR [5]. Results and Discussion In this in vitro work, we compared the organic zwitterionic coating – poly(sulfobetaine methacrylate) [poly(SBMA)] hydrogel – with the synthetic coating – PEG – in reducing adhesion and activation of inflammatory and pro-fibrotic cells, early hallmarks of the FBR, to Polyimide surfaces. Firstly, the hydrogel was synthesized and characterized Figure 1. Adhesion, viability and morphology of human myofibroblasts on PEG-, SBMA hydrogel-coated and polystyrene surfaces were evaluated via high-content analysis (HCA). Activation of M1 pro-inflammatory macrophages cultured on hydrogels was assessed through HCA. We performed a coating of Polyimide surfaces with a thin film of the hydrogel through covalent bond and analyzed the long-term release of an anti-fibrotic drug from the hydrogel. Conclusions and Outlook Because of the high hydration, biocompatibility, low stiffness, and ultra-low fouling characteristics, the hydrogel allowed lower adhesion and activation of pro-inflammatory and pro-fibrotic cells vs. polystyrene controls. Our soft zwitterionic hydrogel could potentially outperform PEG as more suitable dressing of intraneural electrodes for reducing the FBR and could be envisioned as long-term delivery system for gradual and controlled anti-inflammatory and anti-fibrotic drug release in vivo.
A poly(SBMA) zwitterionic hydrogel coating of polyimide surfaces for reducing the foreign body reaction to implanted neural electrodes
Gori M.
Primo
Writing – Review & Editing
;Rainer A.Methodology
;
2022
Abstract
Introduction Invasive intraneural electrodes can control advanced neural-interfaced prostheses in human amputees [1]. Nevertheless, in chronic implants the gradual loss of functionality due to the progressive formation of a fibrotic capsule can ultimately isolate the electrode surface from the surrounding tissue. This is due to a nonspecific inflammatory response called foreign-body reaction (FBR) [2,3]. Poly(ethylene glycol) (PEG) is one of the most widely used low-fouling coatings of implantable devices. However, PEG can be easily encapsulated and susceptible to oxidative damage in long-term in vivo applications [4]. Recently, sulfobetaine-based zwitterionic hydrogels have emerged as an important class of robust ultra- low fouling biomaterials that ameliorate the performance of metal electrodes, holding great potential to reduce the FBR [5]. Results and Discussion In this in vitro work, we compared the organic zwitterionic coating – poly(sulfobetaine methacrylate) [poly(SBMA)] hydrogel – with the synthetic coating – PEG – in reducing adhesion and activation of inflammatory and pro-fibrotic cells, early hallmarks of the FBR, to Polyimide surfaces. Firstly, the hydrogel was synthesized and characterized Figure 1. Adhesion, viability and morphology of human myofibroblasts on PEG-, SBMA hydrogel-coated and polystyrene surfaces were evaluated via high-content analysis (HCA). Activation of M1 pro-inflammatory macrophages cultured on hydrogels was assessed through HCA. We performed a coating of Polyimide surfaces with a thin film of the hydrogel through covalent bond and analyzed the long-term release of an anti-fibrotic drug from the hydrogel. Conclusions and Outlook Because of the high hydration, biocompatibility, low stiffness, and ultra-low fouling characteristics, the hydrogel allowed lower adhesion and activation of pro-inflammatory and pro-fibrotic cells vs. polystyrene controls. Our soft zwitterionic hydrogel could potentially outperform PEG as more suitable dressing of intraneural electrodes for reducing the FBR and could be envisioned as long-term delivery system for gradual and controlled anti-inflammatory and anti-fibrotic drug release in vivo.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.