Here we focus on the FBR challenge for peripheral nervous system implants.Īcute inflammatory responses and cell death in the surrounding area of a peripheral nerve implant, initiated by the surgical implantation procedure, can impede neural regeneration and intimate nerve-implant integration. 9 The FBR challenge must be overcome to allow for next-generation neural interface technologies to achieve their promised therapeutic potential. 8 The FBR is thought to arise from a variety of interrelated factors including mechanical mismatch of the implant-tissue interface, implant biomaterial bulk and/or surface incompatibility, damage during implantation, and micro-motion of the implanted device. 7 The FBR can include non-specific protein absorption (i.e., biofouling), fibrotic encapsulation, chronic inflammation, and neuronal cell death near the implants. 5, 6 However, a major challenge for many biomedical devices is the foreign body reaction (FBR) that can result in loss of function or device failure, and for neural interfaces these problems can include deterioration of recordable neural signals, loss of stimulation effectiveness, and increased background noise over the duration of the implant. Next generation neural interfaces aim to improve therapeutic outcomes by increasing device channel counts to interface with larger numbers of axons, using minimally invasive and less damaging implantation protocols, and improving chronic reliability so devices can maintain functionality for the patient’s lifetime. 1 There are several examples of neural interfaces that are successfully commercialized including cochlear implants to restore function of the damaged inner ear, 2 deep brain stimulators to manage Parkinson’s disease, 3 and retinal prostheses to restore vision. Recorded bioelectrical signals are passed to computerized signal processors that can translate and direct desired motor function (e.g., movement in a robotic prothesis) or the reverse process where nerves are electrically stimulated to provide feedback to the patient for modulating neural activity and/or restoring sensory function. An ideal neural interface can restore both sensory and motor function through electrical stimulation of the nerves (input) and recording bioelectrical signals (output) from axonal impulses. There is a growing need for bioelectronic neural interface technology to enable effective and chronic communication between a patient’s nerve fibers (i.e., axons) and computer platforms to provide a variety of therapeutic benefits (e.g., restoration of vision, improved prosthetic control). Our results showed although surface patterning is a strong physical tool for modulating cell behaviour, responses to micropatterns are highly dependent on the cell type. No statistically significant trends or correlations between cellular responses and geometrical parameters were identified because mammalian cells can change their morphology dependent on their environment in a manner dissimilar to bacteria. 20 μm wide channels spaced 2 μm apart were found to promote Schwann cell attachment and alignment while simultaneously inhibiting fibroblasts and warrant further in vivo study on neural interface devices. In general, Schwann cells were found to be more metabolically active and aligned than fibroblasts when compared between the same pattern. In vitro cell assays were used to screen the effect of Sharklet™ and channel micropatterns of varying dimensions from 2 – 20 μm on fibroblast and Schwann cell metrics (e.g., morphology/alignment, nuclei count, metabolic activity), and a hierarchical ANOVA was used to compare treatments. We hypothesized that a Sharklet™ micropattern could be identified that inhibited fibroblasts partially responsible for FBR, while promoting Schwann cell proliferation and alignment. Parallel microchannels have been shown to modulate neuronal cell alignment and axonal growth, and Sharklet™ microtopographies of targeted feature sizes can modulate bio-adhesion of an array of bacteria, marine organisms, and epithelial cells due to their unique geometry. Engineered microtopographies (e.g., surface patterning) could alleviate these challenges by manipulating cellular responses to the implanted device. The chronic reliability of bioelectronic neural interfaces has been challenged by foreign body reactions (FBRs) resulting in fibrotic encapsulation and poor integration with neural tissue.
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