Julian H. George

Cells are inherently sensitive to local mesoscale, microscale, and nanoscale patterns of chemistry and topography. We review current approaches to control cell behavior through the nanoscale engineering of materials surfaces. Far-reaching implications are emerging for applications including medical implants, cell supports, and materials that can be used as instructive three-dimensional environments for tissue regeneration.

The field of tissue engineering places complex demands on the materials it uses. The materials chosen to support the intricate processes of tissue development and maintenance need to have properties which serve both the bulk mechanical and structural requirements of the target tissue, as well as enabling interactions with cells at the molecular scale. In this critical review we explore how synthetic polymers can be utilised to meet the needs of tissue engineering applications, and how biomimetic principles can be applied to polymeric materials in order to enhance the biological response to scaffolding materials (105 references).

The development of techniques to create and use multiphase microstructured hydrogels (granular hydrogels or microgels) has enabled the generation of cultures with more biologically relevant architecture and use of structured hydrogels is especially pertinent to the development of new types of central nervous system (CNS) culture models and therapies. We review material choice and the customisation of hydrogel structure, as well as the use of hydrogels in developmental models. Combining the use of structured hydrogel techniques with developmentally relevant tissue culture approaches will enable the generation of more relevant models and treatments to repair damaged CNS tissue architecture.

Primary rodent neurons and immortalised cell lines have overwhelmingly been used for in vitro studies of traumatic injury to peripheral and central neurons, but have some limitations of physiological accuracy. Motor neurons (MN) derived from human induced pluripotent stem cells (iPSCs) enable the generation of cell models with features relevant to human physiology. To facilitate this, it is desirable that MN protocols both rapidly and efficiently differentiate human iPSCs into electrophysiologically active MNs. In this study, we present a simple, rapid protocol for differentiation of human iPSCs into functional spinal (lower) MNs, involving only adherent culture and use of small molecules for directed differentiation, with the ultimate aim of rapid production of electrophysiologically functional cells for short-term neural injury experiments. We show successful differentiation in two unrelated iPSC lines, by quantifying neural-specific marker expression, and by evaluating cell functionality at different maturation stages by calcium imaging and patch clamping. Differentiated neurons were shown to be electrophysiologically altered by uniaxial mechanical deformation. Spontaneous network activity decreased with applied stretch, indicating aberrant network connectivity. These results demonstrate the feasibility of this rapid, simple protocol for differentiating iPSC-derived MNs, suitable for in vitro neural injury studies focussing on electrophysiological alterations caused by mechanical deformation or trauma.