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Bioengineering systems have transformed scientific knowledge of cellular behaviors in the nervous system (NS) and pioneered innovative, regenerative therapies to treat adult neural disorders. Microscale systems with characteristic lengths of single to hundreds of microns have examined the development and specialized behaviors of numerous neuromuscular and neurosensory components of the NS. The visual system is comprised of the eye sensory organ and its connecting pathways to the visual cortex. Significant vision loss arises from dysfunction in the retina, the photosensitive tissue at the eye posterior that achieves phototransduction of light to form images in the brain. Retinal regenerative medicine has embraced microfluidic technologies to manipulate stem-like cells for transplantation therapies, where de/differentiated cells are introduced within adult tissue to replace dysfunctional or damaged neurons. Microfluidic systems coupled with stem cell biology and biomaterials have produced exciting advances to restore vision. The current article reviews contemporary microfluidic technologies and microfluidics-enhanced bioassays, developed to interrogate cellular responses to adult retinal cues. The focus is on applications of microfluidics and microscale assays within mammalian sensory retina, or neuro retina, comprised of five types of retinal neurons (photoreceptors, horizontal, bipolar, amacrine, retinal ganglion) and one neuroglia (Müller), but excludes the non-sensory, retinal pigmented epithelium.
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Three-Dimensionally Printed Microsystems to Facilitate Flow-Based Study of Cells from Neurovascular Barriers of the Retina
Rapid prototyping has produced accessible manufacturing methods that offer faster and more cost-effective ways to develop microscale systems for cellular testing. Commercial 3D printers are now increasingly adapted for soft lithography, where elastomers are used in tandem with 3D-printed substrates to produce in vitro cell assays. Newfound abilities to prototype cellular systems have begun to expand fundamental bioengineering research in the visual system to complement tissue engineering studies reliant upon complex microtechnology. This project used 3D printing to develop elastomeric devices that examined the responses of retinal cells to flow. Our experiments fabricated molds for elastomers using metal milling, resin stereolithography, and fused deposition modeling via plastic 3D printing. The systems were connected to flow pumps to simulate different flow conditions and examined phenotypic responses of endothelial and neural cells significant to neurovascular barriers of the retina. The results indicated that microdevices produced using 3D-printed methods demonstrated differences in cell survival and morphology in response to external flow that are significant to barrier tissue function. Modern 3D printing technology shows great potential for the rapid production and testing of retinal cell responses that will contribute to both our understanding of fundamental cell response and the development of new therapies. Future studies will incorporate varied flow stimuli as well as different extracellular matrices and expanded subsets of retinal cells.
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- Award ID(s):
- 2243644
- PAR ID:
- 10647001
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- Micromachines
- Volume:
- 15
- Issue:
- 9
- ISSN:
- 2072-666X
- Page Range / eLocation ID:
- 1103
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/mi15091103
