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Biomimetic scaffolds for spinal cord applications exhibit stiffness-dependent immunomodulatory and neurotrophic characteristics

journal contribution
posted on 03.03.2022, 09:01 authored by Ian WoodsIan Woods, Cian O'Connor, Lisa Frugoli, Sean Kerr, Javier Gutierrez Gonzalez, Martyna StasiewiczMartyna Stasiewicz, Tara McGuireTara McGuire, Brenton CavanaghBrenton Cavanagh, Alan HibbittsAlan Hibbitts, Adrian DervanAdrian Dervan, Fergal O'BrienFergal O'Brien
After spinal cord injury (SCI), tissue engineering scaffolds offer a potential bridge for regeneration across the lesion and support repair through proregenerative signaling. Ideal biomaterial scaffolds that mimic the physicochemical properties of native tissue have the potential to provide innate trophic signaling while also minimizing damaging inflammation. To address this challenge, taking cues from the spinal cord's structure, the proregenerative signaling capabilities of native cord components are compared in vitro. A synergistic mix of collagen-IV and fibronectin (Coll-IV/Fn) is found to optimally enhance axonal extension from neuronal cell lines (SHSY-5Y and NSC-34) and induce morphological features typical of quiescent astrocytes. This optimal composition is incorporated into hyaluronic acid scaffolds with aligned pore architectures but varying stiffnesses (0.8–3 kPa). Scaffolds with biomimetic mechanical properties (<1 kPa), functionalized with Coll-IV/Fn, not only modulate primary astrocyte behavior but also stimulate the production of anti-inflammatory cytokine IL-10 in a stiffness-dependent manner. Seeded SHSY-5Y neurons generate distributed neuronal networks, while softer biomimetic scaffolds promote axonal outgrowth in an ex vivo model of axonal regrowth. These results indicate that the interaction of stiffness and biomaterial composition plays an essential role in vitro in generating repair-critical cellular responses and demonstrates the potential of biomimetic scaffold design.

Funding

Irish Rugby Football Union Charitable Trust (IRFU-CT)

Advanced Materials and Bioengineering Research (AMBER) Centre through Science Foundation Ireland (SFI/12/RC/2278)

Anatomical Society Student Fellowship

History

Comments

This is the peer reviewed version of the following article: Woods I. et al. Biomimetic scaffolds for spinal cord applications exhibit stiffness-dependent immunomodulatory and neurotrophic characteristics. Adv Healthc Mater. 2022;11(3):e2101663, which has been published in final form at https://doi.org/10.1002/adhm.202101663 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Published Citation

Woods I. et al. Biomimetic scaffolds for spinal cord applications exhibit stiffness-dependent immunomodulatory and neurotrophic characteristics. Adv Healthc Mater. 2022;11(3):e2101663

Publication Date

16 November 2021

PubMed ID

34784649

Department/Unit

  • Amber (Advanced Material & Bioengineering Research) Centre
  • Anatomy and Regenerative Medicine
  • Tissue Engineering Research Group (TERG)

Research Area

  • Immunity, Infection and Inflammation
  • Respiratory Medicine
  • Chemistry and Pharmaceutical Sciences
  • Biomaterials and Regenerative Medicine

Publisher

Wiley

Version

  • Accepted Version (Postprint)