Institute of Biochemistry and Cell Biology (IBBC)-National Research Council (CNR), International Campus "A. Buzzati-Traverso", Via E. Ramarini 32, 00015 Rome, Italy.
Laboratory of Regenerative Orthopaedic, Research Unit of Orthopaedic Surgery, Campus Bio-Medico University of Rome, 00128 Rome, Italy.
Molecules. 2022 May 13;27(10):3126. 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.
侵入性神经内电极可以控制人类截肢者的先进神经接口假肢。然而，在慢性植入物中，纤维囊的逐渐形成会逐渐使电极表面与周围组织隔离，导致功能丧失。这是由于一种称为异物反应（FBR）的非特异性炎症反应。可植入设备中常用的聚（乙二醇）（PEG）基低污涂层很容易被包裹，并且在长期体内应用中容易受到氧化损伤。最近，基于磺酸甜菜碱的两性离子水凝胶已成为一类重要的坚固超低污生物材料，具有减轻 FBR 的巨大潜力。这项体外初步研究的目的是评估有机两性离子-聚（磺酸甜菜碱甲基丙烯酸酯）[聚（SBMA）]-水凝胶是否可以作为聚酰亚胺（PI）基神经内电极的合适涂层，以减少 FBR。我们首先通过机械特性（即杨氏模量）合成和分析了水凝胶。然后，我们通过细胞活力测定、共聚焦荧光显微镜和氧化应激产物的高内涵分析，证明与 PEG 涂层和聚苯乙烯表面相比，水凝胶上纤维原性和成纤维细胞（即人肌成纤维细胞和巨噬细胞）的粘附和激活减少。有趣的是，我们通过共价键成功地在 PI 表面涂覆了一层水凝胶薄膜，并通过水接触角测量证明了其高亲水性。重要的是，我们展示了水凝胶从长期释放抗纤维化药物（即依维莫司）。由于低刚度、生物相容性、高水合作用和超低污特性，我们的两性离子水凝胶可以被设想为用于体内缓慢和持续抗炎和抗纤维化药物释放的长期基于扩散的输送系统。
