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.