Open-Spaced Ridged Hydrogel Scaffolds Containing TiO2-Self-Assembled Monolayer of Phosphonates Promote Regeneration and Recovery Following Spinal Cord Injury

Author:

Siddiqui Ahad M.1ORCID,Thiele Frederic12,Stewart Rachel N.13ORCID,Rangnick Simone12,Weiss Georgina J.14,Chen Bingkun K.1,Silvernail Jodi L.1,Strickland Tammy13ORCID,Nesbitt Jarred J.1,Lim Kelly5,Schwarzbauer Jean E.6ORCID,Schwartz Jeffrey5,Yaszemski Michael J.7,Windebank Anthony J.1,Madigan Nicolas N.1ORCID

Affiliation:

1. Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA

2. Program in Human Medicine, Paracelsus Medical Private University, 5020 Salzburg, Austria

3. Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, H91 TK33 Galway, Ireland

4. Program in Human Medicine, Paracelsus Medical Private University, 90419 Nuremberg, Germany

5. Department of Chemistry, Princeton University, Princeton, NJ 08544, USA

6. Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA

7. Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA

Abstract

The spinal cord has a poor ability to regenerate after an injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treating a spinal cord injury (SCI) is the use of biomaterials. We have developed a novel hydrogel scaffold fabricated from oligo(poly(ethylene glycol) fumarate) (OPF) as a 0.08 mm thick sheet containing polymer ridges and a cell-attractive surface on the other side. When the cells are cultured on OPF via chemical patterning, the cells attach, align, and deposit ECM along the direction of the pattern. Animals implanted with the rolled scaffold sheets had greater hindlimb recovery compared to that of the multichannel scaffold control, which is likely due to the greater number of axons growing across it. The immune cell number (microglia or hemopoietic cells: 50–120 cells/mm2 in all conditions), scarring (5–10% in all conditions), and ECM deposits (Laminin or Fibronectin: approximately 10–20% in all conditions) were equal in all conditions. Overall, the results suggest that the scaffold sheets promote axon outgrowth that can be guided across the scaffold, thereby promoting hindlimb recovery. This study provides a hydrogel scaffold construct that can be used in vitro for cell characterization or in vivo for future neuroprosthetics, devices, or cell and ECM delivery.

Funder

New Jersey Commission on Spinal Cord Research

National Center for Advancing Translational Sciences

Mayo Clinic Benefactor Funded Career Development Award–Regenerative Medicine Initiative, and National Institute of Arthritis and Musculoskeletal and Skin Disease

Bowen Foundation

Kipnis Foundation

Nemitz Foundation

Mayo Clinic Center for Regenerative Medicine

New Ideas in the Natural Sciences Award from the Princeton Dean of Research

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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