Composite biomaterial scaffolds enable patterning of tissue architecture and cell identity
Regional diffusion gradients of molecular factors provide developmental cues in neural tissue organoids
Three-dimensional culture of stem cells in biomaterials has recently
enabled the formation of complex cellular structures and miniature
organoid tissues, including tissues resembling brain, spinal cord,
retina, liver, and kidney. In order to improve this technology further,
research published in the Journal of Tissue Engineering describes
new designs for unique biomaterial scaffolds that incorporate patterned
architectures and regional compartments of signaling factors that can
more intricately guide tissue development. These designs enable more
comprehensive control over cell fate and tissue architecture, and also
establish a platform for studying the effects of concentration gradients
of a variety of signaling factors on tissue development.
The ability to form specific molecular concentration gradients
within tissue cultures provides several unique advantages and
capabilities. The
compartments of signaling factors that are designed into the synthetic
tissue constructs can form concentration gradients as a result of
natural diffusion behaviors, and these gradients can control numerous
processes like stem cell differentiation, regional identity, axis
patterning, and tissue architecture. As examples, Dr. McMurtrey
describes how regional gradients of sonic hedgehog protein (SHH), wnt
protein (WNT), bone morphogenic protein (BMP), fibroblast growth factor
(FGF), retinoic acid (RA), and reelin protein (RELN) can influence the
formation of the nervous system in both innate neural tissue and in
three-dimensional (3D) organoids. By separating factors into localized
molecular gradients, researchers can mimic developmental cues and can
thereby pattern ventral/dorsal and rostral/caudal aspects of the
organoid tissue.
Importantly, the tissue construct designs presented in the paper
also enable an array of important investigations in tissue development,
disease mechanisms, drug toxicologies, as well as regenerative medicine
applications. The combination of biomaterials with stem cells can
provide many advantages over stem cell applications alone, including
improved cell survival, improved guidance of differentiation processes,
improved cellular integration into host tissue, improved control of
tissue patterning, and improved migration and sprouting of neural
connections. Nevertheless, much research still remains to be done on the
optimal combinations of biomaterials, signaling factors, and
scaffolding architectures needed to optimally prepare cells for
transplantation and integration into specific tissues of the body, and
it is hoped that this technology will someday provide capabilities to
guide reconstruction of neural architecture in the human nervous system.
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Reference: McMurtrey RJ. Multi-Compartmental Biomaterial Scaffolds
for Patterning Neural Tissue Organoids in Models of Neurodevelopment
and Tissue Regeneration. J. Tissue Engineering. 2016; 7:1-8. doi:
10.1177/2041731416671926 PMID: 27766141 arXiv:1610.02543