title: Click-crosslinked injectable hyaluronic acid hydrogel is safe and biocompatible in the intrathecal space for ultimate use in regenerative strategies of the injured spinal cord.
abstract: Traumatic spinal cord injury (SCI) causes damage and degeneration at and around the lesion site resulting in a loss of function. SCI presents a complex regenerative problem due to the multiple aspects of growth inhibition and the heterogeneity in size, shape and extent of injury. Currently, there is no widely accepted treatment strategy available and delivering biomolecules to the central nervous system remains a challenge. With a view towards achieving local release, we designed a hydrogel that can be injected into the intrathecal space. Here we describe the synthesis and characterization of a click-crosslinked hyaluronic acid hydrogel and demonstrate controlled in vitro release of bioactive brain derived neurotrophic factor. Importantly, we demonstrate that this new hydrogel is both biocompatible in the intrathecal space based on immunohistochemistry of the host tissue response and safe based on behavioral analysis of locomotor function.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ont. M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, 160 College Street, Room 530, Toronto, Ont. M5S 3E1, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Führmann
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ont. M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, 160 College Street, Room 530, Toronto, Ont. M5S 3E1, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Obermeyer
authors.affiliation: Krembil Neuroscience Centre, Toronto Western Research Institute, and Department of Surgery, University of Toronto, 399 Bathurst Street, Toronto, Ont. M5T 2S8, Canada.
authors.forename: C H
authors.initials: CH
authors.lastname: Tator
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ont. M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, 160 College Street, Room 530, Toronto, Ont. M5S 3E1, Canada. Electronic address: molly.shoichet@utoronto.ca.
authors.forename: M S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage; D057930:Click Chemistry; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry*; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry; D007278:Injections, Spinal; D019344:Lactic Acid; D008422:Materials Testing; D053758:Nanoparticles; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D044968:Regenerative Medicine / Q000379:methods; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*
chemical_list: D001672:Biocompatible Materials; D019208:Brain-Derived Neurotrophic Factor; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid
keywords: Drug delivery; Hydrogel; Spinal cord injury