Abstract

The characteristics of a material’s surface are extremely important when considering their interactions with biological species. Despite surface chemistry playing a critical role in mediating the responses of cells, there remains no single rule which dictates absolute performance; this is particularly challenging when considering the response of differing cell types to a range of materials. Here, we highlight the functional behavior of neural stem cells presented as neurospheres, with respect to a range of alkane-based self-assembled monolayers presenting different functional groups: OH, CO2H, NH2, phenyl, CH3, SH, and laminin. The influence of chemical cues was examined in terms of neurosphere spreading on each of these defined surfaces (cell adhesion and migration capacity) and neuronal versus glial marker expression. Measurements were made over a time series of 3, 5, and 7 days, showing a dynamic nature to the initial responses observed after seeding. While OH surfaces presented an excellent platform for glial migration, larger proportions of cells expressing neuronal β3-tubulin were found on SH- and laminin-coated surfaces. Axonal elongation was found to be initially similar on all surfaces with neurite lengths having a wider spread predominantly on NH2- and laminin-presenting surfaces. A generalized trend could not be found to correlate cellular responses with surface wettability, lipophilicity (log P), or charge/ionizability (pKa). These results highlight the potential for chemical cues to direct primary neural stem cell responses in contact with the defined materials. New biomaterials which control specific cell culture characteristics in vitro will streamline the up-scale manufacture of cellular therapies, with the enrichment of the required populations resulting from a defined material interaction.

Highlights

  • The manufacture of cells at scale is of great importance in the advancing of fields of regenerative medicine and tissue engineering

  • Specific cell−biomaterial interactions are of absolute value to inform advanced biomaterial development, with surface chemistry playing a major role in the initial interactions and ensuing cell responses

  • There are a plethora of methods to assess such a response, here we examined the expression for the well-understood glial-derived growth factor (GFAP) and β3-tubulin markers, as well as the neurosphere-spreading area and neurite length characteristics

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Summary

Introduction

The manufacture of cells at scale is of great importance in the advancing of fields of regenerative medicine and tissue engineering. Following the clinical application of cellular therapies in a host environment, there is little to no “control” of their responses; they require continued instruction/direction in order for the developing tissue to present the required cell type(s), architecture, and function. This is important in complex tissues such as within the neural niche.[2] Specific cell−biomaterial interactions are of absolute value to inform advanced biomaterial development, with surface chemistry playing a major role in the initial interactions and ensuing cell responses

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