Evaluation of in situ gelling chitosan-PEG copolymer for use in the spinal cord.

Abstract

The goal of the present work was to characterize a hydrogel material for localized spinal cord delivery. To address spinal cord injuries, an injectable in situ gelling system was tested utilizing a simple, effective, and rapid cross-linking method via Michael addition. Thiolated chitosan material and maleimide-terminated polyethylene glycol material were mixed to form a hydrogel and evaluated in vitro and in vivo. Three distinct thiolated chitosan precursors were made by varying reaction conditions; a modification of chitosan with Traut's reagent (2-iminothiolane) displayed the most attractive hydrogel properties once mixed with polyethylene glycol. The final hydrogel chosen for animal testing had a swelling ratio (Q) of 57.5 ± 3.4 and elastic modulus of 378 ± 72 Pa. After confirming low cellular toxicity in vitro, the hydrogel was injected into the spinal cord of rats for 1 and 2 weeks to assess host reaction. The rats displayed no overt functional deficits due to injection following initial surgical recovery and throughout the 2-week period after for both the saline-injected sham group and hydrogel-injected group. The saline and hydrogel-injected animals both showed a similar response from ED1+ microglia and GFAP overexpression. No significant differences were found between saline-injected and hydrogel-injected groups for any of the measures studied, but there was a trend toward decreased affected area size from 1 to 2 weeks in both groups. Access to the central nervous system is limited by the blood-brain barrier for noninvasive therapies; further development of the current system for localized drug or cellular delivery has the potential to shape treatments of spinal cord injury.

• Authors: Ashley E Mohrman, Mahmoud Farrag, Rachel K Grimm, Nic D Leipzig
• Journal: Journal of biomaterials applications (J Biomater Appl) Vol. 33 Issue 3 Pg. 435-446 (09 2018) ISSN: 1530-8022 [Electronic] England
• PMID: 30111249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biocompatible Materials
• Hydrogels
• PEG-chitosan copolymer
• Polyethylene Glycols
• Chitosan

Topics

• Animals
• Biocompatible Materials (chemistry, therapeutic use)
• Cells, Cultured
• Chitosan (administration & dosage, analogs & derivatives, chemistry, therapeutic use, toxicity)
• Elastic Modulus
• Humans
• Hydrogels (administration & dosage, chemistry, therapeutic use, toxicity)
• Injections
• Male
• Materials Testing
• Polyethylene Glycols (administration & dosage, chemistry, therapeutic use, toxicity)
• Rats
• Rats, Wistar
• Spinal Cord Injuries (pathology, therapy)