Release of Nerve Growth Factor from HEMA Hydrogel-Coated Substrates and Its Effect on the Differentiation of Neural Cells

Abstract

Local pharmacological intervention may be needed to ensure the long-term performance of neural prosthetic devices because of insertion-related neuron loss and reactive cell responses that form compact sheaths, leading to decreased device performance. We propose that local delivery of neurotrophins would enhance neuron survival and promote neuron sprouting toward device electrodes, thus providing improved electrode-neuron communication and device performance for recording and stimulating CNS activity. In this study, three different types of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels were developed and assessed for storage capacity and release rates of the neurotrophin, nerve growth factor (NGF). Additionally, a method was developed for routine coating of microfabricated neuroprosthetic devices with the different pHEMA hydrogels. Biological responses to hydrogel-delivered NGF from the devices were measured using primary cell cultures of dorsal root ganglion (DRG) neurons. Neuron process growth was used to assess biological responses to released NGF. When targeted media concentrations were the same, responses to bath-applied NGF and NGF released from pHEMA hydrogels were not significantly different. When NGF was released from lysine-conjugated pHEMA hydrogels, a significant increase in process growth was observed. Our studies demonstrate that pHEMA coatings can be used on neural devices consistent with the needs for local neurotrophin delivery in the brain.

Conducting polymer-hydrogels for medical electrode applications

“…Ideal neural interfacing materials should be designed to promote targeted cell attachment and ingrowth of neural tissue to the electrode interface through release of appropriate biomolecules, such as nerve growth factor [56,57,69]. Characterization of the cell response is vital to developing an optimal neural interface material.…”

“…They are commonly used in drug delivery applications, and have been proposed as a means of releasing neurotrophins in neural stimulating electrodes [55]. The release of other growth factors, proteins or drugs could be used to discourage fibrous encapsulation and encourage the growth of neural cells into the implant [56,57].…”

Determination of the molar mass of surface-grafted weak polyelectrolyte brushes using force spectroscopy

“…In recent years, polymer brushes have been shown to be a useful class of materials for many medical and biological applications [13,14]. For example, custom synthetic polymers have great potential in drug delivery and molecular recognition [15], and tethering polymer chains onto surfaces can effectively reduce friction [16,17], and control adhesion [18][19][20].…”

Controlled delivery for neuro-bionic devices

“…hydrogel coatings with lysine resulted in more extended release of NGF, while introducing macroporosity into the pHEMA hydrogel coatings shortened the release of NGF [31].…”

“…Three approaches are reviewed here. The first involves drug-eluting structures formulated with anti-inflammatory drugs [21,22,23,24,25] and neurotrophin-eluting hydrogels [26,27,28,29,30,31]. The second approach involves integration of microfluidic channels into neural prostheses for in situ delivery of bioactive molecules with high temporal and spatial resolution [32,33,34,35,36,37,38,39].…”