![Modulating Neuroinflammation with Porous Templated Scaffolds
Ian Dryg1, Zin Khaing2, Le Zhen3, Dane DeWees2, Lindsay Cates2, James Bryers1, Buddy Ratner1,3, Christoph Hofstetter2
Excessive Neuroinflammation
Inhibits SCI Healing and Brain
Electrode Performance
Results
Porous Templated Scaffolds
can Modulate Inflammatory
Cell Phenotype
1 Dept. of Bioengineering, University of Washington, Seattle, WA, USA; 2 Dept. of Neurological Surgery, University of Washington Medical Center, Seattle, WA, USA;
3 Dept. of Chemical Engineering, University of Washington, Seattle, WA, USA
No treatments have demonstrated neurological recovery or meaningful
increase in function in humans1. Tissue Engineered Scaffolds are a
promising area of research that can be used to bridge the lesion, to deliver
stem cells or biomolecules, or to modulate cell activity through their
microenvironments.
[1] Thuret S, Moon LD, and Gage FH (2006) Therapeutic interventions after spinal cord injury. Nat Rev Neurosci 7:628–643.
[2] Sussman, E. M., Halpin, M. C., Muster, J., Moon, R. T., & Ratner, B. D. (2014). Porous implants modulate healing and
induce shifts in local macrophage polarization in the foreign body reaction. Ann Biomed Eng, 42(7), 1508-1516.
doi:10.1007/s10439-013-0933-0
[3] Basso, D. M., Beattie, M. S., & Bresnahan, J. C. (1995). A sensitive and reliable locomotor rating scale for open field
testing in rats. J Neurotrauma, 12(1), 1-21. doi:10.1089/neu.1995.12.1
• CNS Tissue is sensitive to stiffness
• Methods of quantifying Immune Modulation
HISTOLOGY
LABELS
GFAP (Astrocytes)
CD68 (Microglia &
Macrophages)
Hoescht (Cell
Nuclei)
Porous Templated Scaffolds (PTS) are structurally controlled porous
polymers that integrate and heal in multiple in vivo environments.
Maximum vascular density, minimum fibrosis, and modulation of
macrophages towards a healing phenotype are always noted for 35
µm PTS2, regardless of the polymer used or the implant site.
However, PTS have never been tested in the Central Nervous System.
Neural interfaces could restore
mobility and independence for
patients with neurological
conditions such as SCI, stroke, or
limb loss. However, unstable neural
recording performance remains
unresolved. “Glial scarring”
develops around implants, leading
to time-dependent declines in
electrode performance.
Cortical Implants
Spinal Cord Injury
Porous Cortical Implants to reduce
encapsulation of neural electrodes
Porous Scaffolds
to improve healing after Spinal Cord Injury
Discussion
Future Work
References
No Implant
Solid pHEMAPorous (40µm) pHEMA
BBB Score3: 0 – 21
• Measures hind limb function after SCI
• 0 = no functionality
• 21 = fully functional
0
7
14
21
BBBScore
Functional Recovery 2 weeks post-SCI
No Implant
Solid pHEMA
Porous (40 um)
pHEMA
Cortical ImplantsSpinal Cord Injury
• Make scaffolds softer (CNS ~8kPa, wet PTS ~100kPa)
• Assess macrophage polarization (Arg1, iNOS)
• Implant PTS within Spinal Cord Transection
• Cortical Implant study
• Experiment with conducting polymer scaffolds
Plan:
• Implant for 4 weeks
• Monitor over time:
• Impedance
• SNR
• # Single Units
• Tissue Histology](https://image.slidesharecdn.com/2b4d0c40-f4af-4b8f-abd1-00413345be99-170107073718/85/Scaffolds-Presentation-UW-1-320.jpg)
Scaffolds Presentation-UW
- 1. Modulating Neuroinflammation with Porous Templated Scaffolds Ian Dryg1, Zin Khaing2, Le Zhen3, Dane DeWees2, Lindsay Cates2, James Bryers1, Buddy Ratner1,3, Christoph Hofstetter2 Excessive Neuroinflammation Inhibits SCI Healing and Brain Electrode Performance Results Porous Templated Scaffolds can Modulate Inflammatory Cell Phenotype 1 Dept. of Bioengineering, University of Washington, Seattle, WA, USA; 2 Dept. of Neurological Surgery, University of Washington Medical Center, Seattle, WA, USA; 3 Dept. of Chemical Engineering, University of Washington, Seattle, WA, USA No treatments have demonstrated neurological recovery or meaningful increase in function in humans1. Tissue Engineered Scaffolds are a promising area of research that can be used to bridge the lesion, to deliver stem cells or biomolecules, or to modulate cell activity through their microenvironments. [1] Thuret S, Moon LD, and Gage FH (2006) Therapeutic interventions after spinal cord injury. Nat Rev Neurosci 7:628–643. [2] Sussman, E. M., Halpin, M. C., Muster, J., Moon, R. T., & Ratner, B. D. (2014). Porous implants modulate healing and induce shifts in local macrophage polarization in the foreign body reaction. Ann Biomed Eng, 42(7), 1508-1516. doi:10.1007/s10439-013-0933-0 [3] Basso, D. M., Beattie, M. S., & Bresnahan, J. C. (1995). A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma, 12(1), 1-21. doi:10.1089/neu.1995.12.1 • CNS Tissue is sensitive to stiffness • Methods of quantifying Immune Modulation HISTOLOGY LABELS GFAP (Astrocytes) CD68 (Microglia & Macrophages) Hoescht (Cell Nuclei) Porous Templated Scaffolds (PTS) are structurally controlled porous polymers that integrate and heal in multiple in vivo environments. Maximum vascular density, minimum fibrosis, and modulation of macrophages towards a healing phenotype are always noted for 35 µm PTS2, regardless of the polymer used or the implant site. However, PTS have never been tested in the Central Nervous System. Neural interfaces could restore mobility and independence for patients with neurological conditions such as SCI, stroke, or limb loss. However, unstable neural recording performance remains unresolved. “Glial scarring” develops around implants, leading to time-dependent declines in electrode performance. Cortical Implants Spinal Cord Injury Porous Cortical Implants to reduce encapsulation of neural electrodes Porous Scaffolds to improve healing after Spinal Cord Injury Discussion Future Work References No Implant Solid pHEMAPorous (40µm) pHEMA BBB Score3: 0 – 21 • Measures hind limb function after SCI • 0 = no functionality • 21 = fully functional 0 7 14 21 BBBScore Functional Recovery 2 weeks post-SCI No Implant Solid pHEMA Porous (40 um) pHEMA Cortical ImplantsSpinal Cord Injury • Make scaffolds softer (CNS ~8kPa, wet PTS ~100kPa) • Assess macrophage polarization (Arg1, iNOS) • Implant PTS within Spinal Cord Transection • Cortical Implant study • Experiment with conducting polymer scaffolds Plan: • Implant for 4 weeks • Monitor over time: • Impedance • SNR • # Single Units • Tissue Histology