In vivoevaluation of a neural stem cell-seeded prosthesis

Abstract

Neural prosthetics capable of recording or stimulating neuronal activity may restore function for patients with motor and sensory deficits resulting from injury or degenerative disease. However, overcoming inconsistent recording quality and stability in chronic applications remains a significant challenge. A likely reason for this is the reactive tissue response to the devices following implantation into the brain, which is characterized by neuronal loss and glial encapsulation. We have developed a neural stem cell-seeded probe to facilitate integration of a synthetic prosthesis with the surrounding brain tissue. We fabricated parylene devices that include an open well seeded with neural stem cells encapsulated in an alginate hydrogel scaffold. Quantitative and qualitative data describing the distribution of neuronal, glial, and progenitor cells surrounding seeded and control devices is reported over four time points spanning three months. Neuronal loss and glial encapsulation associated with cell-seeded probes were mitigated during the initial week of implantation and exacerbated by six weeks post-insertion compared to control conditions. We hypothesize that graft cells secrete neuroprotective and neurotrophic factors that effect the desired healing response early in the study, with subsequent cell death and scaffold degradation accounting for a reversal of these results later. Applications of this biohybrid technology include future long-term neural recording and sensing studies.

Novel multi-sided, microelectrode arrays for implantable neural applications

“…3(c)). Alternatively, a completely open channel, i.e., no backside, can be used for stem-cell delivery with a dip coating technique (Purcell et al 2009). These cell-delivery structures now incorporate functional electrode sites.…”

Cellular Modulation of Polymeric Device Surfaces: Promise of Adult Stem Cells for Neuro-Prosthetics

“…Previous work from Purcell et al (2009) confirmed that cell-seeded cortical probes have a beneficial effect on the early brain tissue response after implantation. They fabricated parylene devices, which were built-up by an open well seeded with mouse cortical neural stem cells encapsulated in an alginate hydrogel scaffold (Purcell et al, 2009).…”

“…They fabricated parylene devices, which were built-up by an open well seeded with mouse cortical neural stem cells encapsulated in an alginate hydrogel scaffold (Purcell et al, 2009). The study, carried out in a rat model, described an improved healing process over a period of 3 month post-implantation.…”

Neuronal excitability and network formation on optically transparent electrode materials

“…Parylene-C, PDMS and ITO are all transparent, biocompatible candidate materials for the fabrication of “next-generation” electrode arrays[9]–[12]. Each substrate offers unique advantages in addition to their superior optical properties.…”

“…Each substrate offers unique advantages in addition to their superior optical properties. Parylene-C is commonly used as an encapsulation material as it is an electrical insulator which is also biologically and chemically inert [9], [10]. As such, it is a useful barrier to protect electrical components from biological environments while isolating tissue from the potentially toxic products of electrode degradation[10].…”