Combinatorial tissue engineering partially restores function after spinal cord injury

Jeffrey S. Hakim, Brian R. Rodysill, Bingkun K. Chen, Ann M. Schmeichel, Michael J Yaszemski, Anthony John Windebank, Nicolas N. Madigan

Research output: Contribution to journalArticle

Abstract

Hydrogel scaffolds provide a beneficial microenvironment in transected rat spinal cord. A combinatorial biomaterials-based strategy provided a microenvironment that facilitated regeneration while reducing foreign body reaction to the three-dimensional spinal cord construct. We used poly lactic-co-glycolic acid microspheres to provide sustained release of rapamycin from Schwann cell (SC)-loaded, positively charged oligo-polyethylene glycol fumarate scaffolds. The biological activity and dose-release characteristics of rapamycin from microspheres alone and from microspheres embedded in the scaffold were determined in vitro. Three dose formulations of rapamycin were compared with controls in 53 rats. We observed a dose-dependent reduction in the fibrotic reaction to the scaffold and improved functional recovery over 6 weeks. Recovery was replicated in a second cohort of 28 animals that included retransection injury. Immunohistochemical and stereological analysis demonstrated that blood vessel number, surface area, vessel diameter, basement membrane collagen, and microvessel phenotype within the regenerated tissue was dependent on the presence of SCs and rapamycin. TRITC-dextran injection demonstrated enhanced perfusion into scaffold channels. Rapamycin also increased the number of descending regenerated axons, as assessed by Fast Blue retrograde axonal tracing. These results demonstrate that normalization of the neovasculature was associated with enhanced axonal regeneration and improved function after spinal cord transection.

Original languageEnglish (US)
JournalJournal of Tissue Engineering and Regenerative Medicine
DOIs
StatePublished - Jan 1 2019

Fingerprint

Sirolimus
Tissue Engineering
Spinal Cord Injuries
Tissue engineering
Scaffolds
Microspheres
Rats
Regeneration
Spinal Cord
Recovery
Dextran
Blood vessels
Foreign-Body Reaction
Scaffolds (biology)
Bioactivity
Fumarates
Collagen
Biomaterials
Hydrogels
Polyethylene glycols

Keywords

  • biodegradable
  • combination product
  • nervous system
  • regeneration
  • scaffold
  • spinal cord injury

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

Cite this

Combinatorial tissue engineering partially restores function after spinal cord injury. / Hakim, Jeffrey S.; Rodysill, Brian R.; Chen, Bingkun K.; Schmeichel, Ann M.; Yaszemski, Michael J; Windebank, Anthony John; Madigan, Nicolas N.

In: Journal of Tissue Engineering and Regenerative Medicine, 01.01.2019.

Research output: Contribution to journalArticle

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