title: 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.
authors.affiliation: Department of Materials Science and Engineering, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Shalin J
authors.initials: SJ
authors.lastname: Jhaveri
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hynd
authors.forename: Natalie
authors.initials: N
authors.lastname: Dowell-Mesfin
authors.forename: James N
authors.initials: JN
authors.lastname: Turner
authors.forename: William
authors.initials: W
authors.lastname: Shain
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Ober
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry*; D015394:Molecular Structure; D020932:Nerve Growth Factor / Q000737:chemistry* / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D013997:Time Factors
chemical_list: D020099:Coated Materials, Biocompatible; D008689:Methacrylates; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C005044:hydroxyethyl methacrylate; D020932:Nerve Growth Factor