Positively Charged Oligo[Poly(Ethylene Glycol) Fumarate] Scaffold Implantation Results in a Permissive Lesion Environment after Spinal Cord Injury in Rat

Jeffrey S. Hakim, Melika Esmaeili Rad, Peter J. Grahn, Bingkun K. Chen, Andrew M. Knight, Ann M. Schmeichel, Nasro A. Isaq, Mahrokh Dadsetan, Michael J Yaszemski, Anthony John Windebank

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Positively charged oligo[poly(ethylene glycol) fumarate] (OPF+) scaffolds loaded with Schwann cells bridge spinal cord injury (SCI) lesions and support axonal regeneration in rat. The regeneration achieved is not sufficient for inducing functional recovery. Attempts to increase regeneration would benefit from understanding the effects of the scaffold and transplanted cells on lesion environment. We conducted morphometric and stereological analysis of lesions in rats implanted with OPF+ scaffolds with or without loaded Schwann cells 1, 2, 3, 4, and 8 weeks after thoracic spinal cord transection. No differences were found in collagen scarring, cyst formation, astrocyte reactivity, myelin debris, or chondroitin sulfate proteoglycan (CSPG) accumulation. However, when scaffold-implanted animals were compared with animals with transection injuries only, these barriers to regeneration were significantly reduced, accompanied by increased activated macrophages/microglia. This distinctive and regeneration permissive tissue reaction to scaffold implantation was independent of Schwann cell transplantation. Although the tissue reaction was beneficial in the short term, we observed a chronic fibrotic host response, resulting in scaffolds surrounded by collagen at 8 weeks. This study demonstrates that an appropriate biomaterial scaffold improves the environment for regeneration. Future targeting of the host fibrotic response may allow increased axonal regeneration and functional recovery.

Original languageEnglish (US)
Pages (from-to)2099-2114
Number of pages16
JournalTissue Engineering - Part A
Volume21
Issue number13-14
DOIs
StatePublished - Jul 1 2015

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Spinal Cord Injuries
Scaffolds
Polyethylene glycols
Rats
Regeneration
Schwann Cells
Cells
Scaffolds (biology)
Collagen
Animals
Recovery
Tissue regeneration
Macrophages
Chondroitin Sulfate Proteoglycans
Debris
Biomaterials
Biocompatible Materials
Cell Transplantation
Microglia
Myelin Sheath

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials

Cite this

Positively Charged Oligo[Poly(Ethylene Glycol) Fumarate] Scaffold Implantation Results in a Permissive Lesion Environment after Spinal Cord Injury in Rat. / Hakim, Jeffrey S.; Esmaeili Rad, Melika; Grahn, Peter J.; Chen, Bingkun K.; Knight, Andrew M.; Schmeichel, Ann M.; Isaq, Nasro A.; Dadsetan, Mahrokh; Yaszemski, Michael J; Windebank, Anthony John.

In: Tissue Engineering - Part A, Vol. 21, No. 13-14, 01.07.2015, p. 2099-2114.

Research output: Contribution to journalArticle

Hakim, Jeffrey S. ; Esmaeili Rad, Melika ; Grahn, Peter J. ; Chen, Bingkun K. ; Knight, Andrew M. ; Schmeichel, Ann M. ; Isaq, Nasro A. ; Dadsetan, Mahrokh ; Yaszemski, Michael J ; Windebank, Anthony John. / Positively Charged Oligo[Poly(Ethylene Glycol) Fumarate] Scaffold Implantation Results in a Permissive Lesion Environment after Spinal Cord Injury in Rat. In: Tissue Engineering - Part A. 2015 ; Vol. 21, No. 13-14. pp. 2099-2114.
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