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Open AccessArticle

Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

1
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S4L8, Canada
2
Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA
3
Faculty of Science, McMaster University, Hamilton, ON L8S4L8, Canada
4
Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, 20-400 Lublin, Poland
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this study.
J. Clin. Med. 2020, 9(4), 1221; https://doi.org/10.3390/jcm9041221
Received: 30 March 2020 / Revised: 12 April 2020 / Accepted: 20 April 2020 / Published: 23 April 2020
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. View Full-Text
Keywords: spinal cord injury; inflammation; immune modulation; serpin; chitosan-collagen hydrogel spinal cord injury; inflammation; immune modulation; serpin; chitosan-collagen hydrogel
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Kwiecien, J.M.; Zhang, L.; Yaron, J.R.; Schutz, L.N.; Kwiecien-Delaney, C.J.; Awo, E.A.; Burgin, M.; Dabrowski, W.; Lucas, A.R. Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function. J. Clin. Med. 2020, 9, 1221.

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