Local serpin treatment via chitosan-collagen hydrogel after spinal cord injury reduces tissue damage and improves neurologic function

Jacek M. Kwiecien, Liqiang Zhang, Jordan R. Yaron, Lauren N. Schutz, Christian J. Kwiecien-Delaney, Enkidia A. Awo, Michelle Burgin, Wojciech Dabrowski, Alexandra R. Lucas

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.

Original languageEnglish (US)
Article number1221
JournalJournal of Clinical Medicine
Volume9
Issue number4
DOIs
StatePublished - Apr 2020

Keywords

  • Chitosan-collagen hydrogel
  • Immune modulation
  • Inflammation
  • Serpin
  • Spinal cord injury

ASJC Scopus subject areas

  • Medicine(all)

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