title: Purine-crosslinked injectable chitosan sponges promote oligodendrocyte progenitor cells' attachment and differentiation.
abstract: Oligodendrocyte Progenitor Cells (OPCs) reside in the central nervous system (CNS) and are responsible for remyelinating axons after a spinal cord injury (SCI). However, the remyelination process is incomplete and abnormal due to the inability of OPCs to fully differentiate at the site of injury. In this study a newly developed injectable chitosan sponge crosslinked using guanosine 5'-diphosphate (GDP) was used to enhance OPC survival, attachment and differentiation. This purine-based biomaterial is the first of its kind and its inception was based on the growing body of literature concerning the role of purinergic signalling in the CNS. GDP-crosslinked chitosan sponges are rapidly-gelling and can be easily administered in situ using an injection system based on a double-lumen design. The chitosan sponges prompted OPC differentiation even in the presence of mitogens. Moreover, neurotrophin-3 (NT-3) was successfully entrapped in the sponges and a sustained release for up to 30 days was achieved. OPCs were shown to differentiate into mature oligodendrocytes that express myelin basic protein (MBP) when cultured on sponges containing NT-3. These findings, along with the suitable physicochemical and biological properties, make these sponges conducive to use as viable therapeutic agents for enhancing remyelination post-SCI.
authors.affiliation: Biomedical Engineering, Duff Medical Building, Room 313, H3A2B4, Montreal, Canada. maryam.tabrizian@mcgill.ca mina.mekhail@mail.mcgill.ca.
authors.forename: Mina
authors.initials: M
authors.lastname: Mekhail
authors.forename: Guillermina
authors.initials: G
authors.lastname: Almazan
authors.forename: Maryam
authors.initials: M
authors.lastname: Tabrizian
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006153:Guanosine Diphosphate / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D004676:Myelin Basic Protein / Q000737:chemistry / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology; D011161:Porifera; D011687:Purines; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism; D013234:Stem Cells / Q000737:chemistry* / Q000502:physiology*
chemical_list: D004676:Myelin Basic Protein; D011687:Purines; D006153:Guanosine Diphosphate; D048271:Chitosan