Nerve growth factor‐immobilized polypyrrole: Bioactive electrically conducting polymer for enhanced neurite extension

Abstract

Biomaterials that present multiple stimuli are attractive for a number of biomedical applications. In particular, electrical and biological cues are important factors to include in interfaces with neurons for applications such as nerve conduits and neural probes. Here, we report the combination of these two stimuli, by immobilizing nerve growth factor (NGF) on the surface of the electrically conducting polymer polypyrrole (PPy). NGF was immobilized using an intermediate linker provided by a layer of polyallylamine conjugated to an arylazido functional group. Upon exposure to UV light and activation of the azido groups, NGF was fixed to the substrate. Three different surface concentrations were obtained (0.21-0.98 ng/mm 2 ) and similar levels of neurite extension were observed on immobilized NGF as with soluble NGF. Additionally, electrical stimulation experiments were conducted with the modified polymer and revealed a 50% increase in neurite outgrowth in PC12 cells compared to experiments without electrical stimulation. This novel modification of PPy provides both electrical and biological stimulation, by presenting tethered growth factors and only producing a small decrease in the material's properties (conductivity ~10 S cm −1 ) when compared to other modification techniques (conductivity ~10 −3 -10 −6 S cm −1 .

Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting polymer

“…3b). PC12 cells are commonly employed as a model system for studies of neuronal development and function; they are also a robust model cell line for evaluating the performance of various platforms for electrically stimulated neurite outgrowth 24,[27][28][29][30] . To compare the performance of our materials with that of other reported platforms, we also adopted PC12 cells in this study to investigate neuron adhesion and differentiation.…”

“…Subsequently, various means of integrating ECPs and biofunctional groups, through physical mixing or chemical immobilization, have been tested [27][28][29][30] . For example, Schmidt and coworkers 27 coated electrospun poly(lactic-co-glycolic acid) nanofibres with polypyrrole and applied this material for neural engineering.…”

“…For example, Schmidt and coworkers 27 coated electrospun poly(lactic-co-glycolic acid) nanofibres with polypyrrole and applied this material for neural engineering. Separately, the same group also immobilized nerve growth factor onto the surface of polypyrroles with the application of an adhesion layer for similar purpose 29 . Wallace and coworkers 31 employed a different approach to form polypyrrole/collagen complexes stabilized through electrostatic interactions.…”

“…Wallace and coworkers 31 employed a different approach to form polypyrrole/collagen complexes stabilized through electrostatic interactions. Unfortunately, these modifications usually lead to relatively lower degrees of enhancement in neurite outgrowth, presumably because of the lower conductivity of these materials 29 .…”

Polymers to direct cell fate by controlling the microenvironment

“…It is unclear what level of complexity will be required for advanced tissue engineering and regenerative medicine applications; however, progress has been achieved to create polymeric systems that alter their properties in response to external or microenvironmental effectors. Polypyrrole based neural interfaces [39] and electroactive self-assembled monolayers [40] respond dynamically to external controls by functioning as electrical relays or surfaces that change conformation, respectively, in response to an electric potential. Other materials have been designed to respond directly to microenvironmental effectors.…”