Neurotrophin‐eluting hydrogel coatings for neural stimulating electrodes

Abstract

Improved sensory and motor prostheses for the central nervous system will require large numbers of electrodes with low electrical thresholds for neural excitation. With the eventual goal of reducing stimulation thresholds, we have investigated the use of biodegradable, neurotrophin-eluting hydrogels (i.e., poly(ethylene glycol)-poly(lactic acid), PEGPLA) as a means of attracting neurites to the surface of stimulating electrodes. PEGPLA hydrogels with release rates ranging from 1.5 to 3 weeks were synthesized. These hydrogels were applied to multielectrode arrays with sputtered iridium oxide charge-injection sites. The coatings had little impact on the iridium oxide electrochemical properties, including charge storage capacity, impedance, and voltage transients during current pulsing. Additionally, we quantitatively examined the ability of neurotrophin-eluting, PEGPLA hydrogels to promote neurite extension in vitro using a PC12 cell culture model. Hydrogels released neurotrophin (nerve growth factor, NGF) for at least 1 week, with neurite extension near that of an NGF positive control and much higher than extension seen from sham, bovine serum albumin-releasing boluses, and a negative control. These results show that neurotrophin-eluting hydrogels can be applied to multielectrode arrays, and suggest a method to improve neuron-electrode proximity, which could result in lowered electrical stimulation thresholds. Reduced thresholds support the creation of smaller electrode structures and high density electrode prostheses, greatly enhancing prosthesis control and function.

Tissue engineering applied to the retinal prosthesis: Neurotrophin-eluting polymeric hydrogel coatings

“…We demonstrated that these hydrogels produce neurite extension in PC12 cells, a model neuron class, in response to elution of nerve growth factor (NGF) [22]. Here, we demonstrate the ability of PEGPLA hydrogels: 1) to emit neurotrophins that have been shown by others to attract retinal neurons (e.g.…”

“…Hydrogel boluses were composed of acrylated poly(ethylene glycol)-poly(lactic acid) (PEGPLA) copolymers synthesized as described previously [22,23]. Two polymers were investigated 1540LA2, containing 1540 MW PEG with 2 lactide groups on each PEG terminus, and 1540LA4 containing 1540 MW PEG with 4 lactide groups on each PEG terminus.…”

“…Two polymers were investigated 1540LA2, containing 1540 MW PEG with 2 lactide groups on each PEG terminus, and 1540LA4 containing 1540 MW PEG with 4 lactide groups on each PEG terminus. Previous investigations of hydrogels composed using these polymers yielded bovine serum albumin (BSA) release durations of 1-3 weeks [22].…”

“…Previously, we developed PEGPLA hydrogels capable of releasing biomolecules for 1-3 weeks [22]. We demonstrated that these hydrogels produce neurite extension in PC12 cells, a model neuron class, in response to elution of nerve growth factor (NGF) [22].…”

The design of electrospun PLLA nanofiber scaffolds compatible with serum-free growth of primary motor and sensory neurons

“…Instead of using primary neurons harvested from the nervous system, most in vitro testing of biomaterials relies on the use of renewable cell lines [1,2,[9][10][11][12][13] or, more rarely, primary cells grown in media supplemented with serum [1,3,14,15]. Both of these approaches have significant drawbacks.…”