A SURFACE DRUG DELIVERY SYSTEM REDUCES THE FOREIGN BODY REACTION AGAINST INTRANEURAL ELECTRODES

When an electrode or medical device is implanted, the body triggers a foreign body reaction (FBR), mainly involving macrophage activation followed by fibroblast differentiation into myofibroblasts to heal tissue and encapsulate the implant. For neural electrodes, this response is detrimental, leading to a loss of functionality. The FBR can be modulated by modifying the surface properties of implanted biomaterials, for example through systems that locally release anti-inflammatory drugs.
In this study, thin-film polyimide devices were chemically modified to covalently bind the glucocorticoid dexamethasone to their surface, enabling focal drug release around the implant. In vitro experiments showed that this strategy reduced the production of pro-inflammatory markers in macrophages activated by LPS. The biocompatibility of the functionalized material was also confirmed by evaluating the viability of DRG neurons.
In vivo implantation of dexamethasone-functionalized polyimide longitudinal intraneural devices resulted in a significant reduction in inflammatory cell infiltration eight weeks after implantation, with better outcomes than systemic dexamethasone administration. This was accompanied by a marked decrease in the thickness of the fibrotic capsule formed around the devices. Furthermore, dexamethasone-functionalized active electrodes based on the TIME design were implanted in the rat sciatic nerve and tested as bidirectional neural interfaces. Compared with bare polyimide electrodes, the functionalized devices showed similar stimulation thresholds and selectivity, indicating that the coating did not affect their electrochemical performance.
Overall, this work highlights the potential of local, long-lasting drug-releasing systems to modulate the inflammatory FBR and improve the long-term biocompatibility and stability of neural electrodes for neuroprosthetic applications.