Since axons do not regenerate appreciably in their native extracellular environment in the central nervous system (CNS); some researchers tried to help patients to restore their lost neural function by integrating prosthetics with their nervous system. However, achieving stable, long-term performance of implanted neural prosthetic devices has been challenging because of implantation related neuron loss and a foreign body response that results in encapsulating glial scar formation.
To improve neuron-prosthesis integration and form chronic, stable interfaces, we investigated the potential of neurotrophin-eluting hydrogel-electrospun fiber mat (EFM) composite coatings. We first synthesized and characterized diacrylate poly(ethylene glycol)-poly(ε-caprolactone) (PEGPCL) and poly(ethylene glycol)-poly(lactic acid) (PEGPLA) block copolymers as hydrogel materials. Then, we fabricated and evaluated poly(ε-caprolactone) (PCL) EFMs with different thicknesses and hydrophobicity.
Followed, we constructed PEGPCL hydrogel-PCL EFM composite materials in two different configurations using UV photo-polymerization, and compared the release kinetics of these composites using bovine serum albumin (BSA) as a model protein. The aggregation status and bioactivity of eluted proteins were also investigated. To better understand the interaction between the eluted protein and composite material, PEGPLA hydrogel-EFM composite materials were formed, comprising of EFMs with different thicknesses and hydrophobicity. The results of composite materials’ swelling and release behaviors demonstrated that both EFM’s thickness and hydrophobicity had significant impact on therapeutics release profile.
In addition, we studied the cell adhesion of SK-N-SH neuroblastoma cells and rat cortical cells to hydrogel-EFM composite materials. The incorporation of external EFMs significantly enhanced cell attachment on composite materials, when compared with PEG and PEGPCL hydrogels. And RNCs preferred to adhere to composite materials composed of hydrophilic EFMs.
Also, PEGPCL hydrogel- PCL EFM composites were applied as coatings for microelectrode arrays (MEAs). Coatings were stable and persisted on electrode surfaces for over 1 month under an agarose gel tissue phantom and over 9 months in a PBS immersion bath. To demonstrate drug release, a neurotrophin, nerve growth factor (NGF), was loaded in the PEGPCL hydrogel layer, and coating cytotoxicity and sustained NGF release were evaluated using a PC12 cell culture model. Quantitative MTT assays showed that these coatings had no significant toxicity toward PC12 cells, and neurite extension at day 7 and 14 confirmed sustained release of NGF at biological significant concentrations for at least 2 weeks. Our results demonstrate that hydrogel-EFM composite materials can be applied to neuroprosthetics as a means to improve neuron-electrode proximity and enhance long-term device performance and function.