Journal
JOURNAL OF CLINICAL MEDICINE
Volume 9, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/jcm9041221
Keywords
spinal cord injury; inflammation; immune modulation; serpin; chitosan-collagen hydrogel
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Funding
- VPC NeuroPath Consulting, Inc.
- Medical University of Lublin, Poland
- Biodesign Institute at Arizona State University, Tempe, AZ, USA
- American Heart Association [17GRNT33460327]
- National Institutes of Health (NIH) [1 R01 AI100987-01A1]
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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 mu g/50 mu L) Serp-1 CCH implanted rats, but not with low dose (10 mu g/50 mu L) 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.
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