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Non-functionalized soft alginate hydrogel promotes locomotor recovery after spinal cord injury in a rat hemimyelonectomy model

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Abstract

Background

Spinal cord injury (SCI) and the consecutive devastating neurological sequelae have an enormous individual and economic impact. Implantation of functionalized hydrogels is a promising approach, because they can serve as a matrix for the regenerating tissue, carry and release bioactive molecules and various cell types. We already demonstrated that non-functionalized soft alginate hydrogel supported axonal outgrowth and protected neurons against oxidative stress in vitro. Here, we investigated the effects of such soft alginate hydrogels on locomotor recovery in small and large spinal cord lesions.

Method

Hemimyelonectomy of 2 mm or 4 mm length was performed in rats and soft alginate hydrogel was implanted. Functional recovery of the hindlimbs was assessed in the open field [Batto Beattie Bresnahan (BBB) score] and using swimming test [Louisville Swim score (LSS)] for 140 days post injury (DPI). Reference histology was performed.

Results

Rats that received an alginate implant into 2 mm spinal cord lesions demonstrated significantly improved locomotor recovery compared to controls detectable already at 10 DPI. At 140 DPI, they reached higher LSS and BBB scores in swimming and open field tests, respectively. However, this beneficial effect of alginate was lacking in animals with larger (4 mm) lesions. Histological examination suggested that fibrous scarring in the spinal cord was reduced after alginate implantation in comparison to controls.

Conclusions

Implantation of soft alginate hydrogel in small spinal cord lesions improved functional recovery. Possible underlying mechanisms include the mechanical stabilization of the wound, reduction of secondary damage and inhibition of fibrous scarring.

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Abbreviations

SCI:

Spinal cord injury

DPI:

Days post injury

LSS:

Louisville Swim score

BBB:

Batto Beattie Bresnahan

Th:

Thoracic level

GDNF:

Glial cell-derived neurotrophic factor

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Acknowledgements

The authors thank Mrs. Elke John und Dr. Roland Jung for providing expertise for animal care.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author information

Author notes

  1. Kerim Hakan Sitoci-Ficici and Marina Matyash contributed equally to this work.

Authors and Affiliations

  1. Neurosurgery, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany

    Kerim Hakan Sitoci-Ficici, Marina Matyash, Ortrud Uckermann, Elke Leipnitz, Robert Later, Gabriele Schackert & Matthias Kirsch

  2. Neuropediatrics, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany

    Marina Matyash & Chrysanthy Ikonomidou

  3. Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, TU Dresden, Dresden, Germany

    Roberta Galli

  4. Department of Neurology, Developmental Brain Injury Laboratory, University of Wisconsin, Madison, WI, USA

    Chrysanthy Ikonomidou

  5. Center for Translational Bone, Joint and Soft Tissue Research, TU Dresden, Dresden, Germany

    Michael Gelinsky

  6. CRTD/DFG-Center for Regenerative Therapies Dresden-Cluster of Excellence, TU Dresden, Dresden, Germany

    Michael Gelinsky & Matthias Kirsch

Authors
  1. Kerim Hakan Sitoci-Ficici
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Correspondence to Matthias Kirsch.

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Sitoci-Ficici, K.H., Matyash, M., Uckermann, O. et al. Non-functionalized soft alginate hydrogel promotes locomotor recovery after spinal cord injury in a rat hemimyelonectomy model. Acta Neurochir 160, 449–457 (2018). https://doi.org/10.1007/s00701-017-3389-4

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