Regenerative therapies for central nervous system diseases: a biomaterials approach

Abstract

The central nervous system (CNS) has a limited capacity to spontaneously regenerate following traumatic injury or disease, requiring innovative strategies to promote tissue and functional repair. Tissue regeneration strategies, such as cell and/or drug delivery, have demonstrated promising results in experimental animal models, but have been difficult to translate clinically. The efficacy of cell therapy, which involves stem cell transplantation into the CNS to replace damaged tissue, has been limited due to low cell survival and integration upon transplantation, while delivery of therapeutic molecules to the CNS using conventional methods, such as oral and intravenous administration, have been limited by diffusion across the blood-brain/spinal cord-barrier. The use of biomaterials to promote graft survival and integration as well as localized and sustained delivery of biologics to CNS injury sites is actively being pursued. This review will highlight recent advances using biomaterials as cell- and drug-delivery vehicles for CNS repair.

Figure 1

Schematic representation of the multiple interactions of the cellular microenvironment, including: cell–cell and cell–substrate interactions where the ECM is defined by its chemical, physical, and mechanical properties: stiffness and elasticity, matrix degradability, permeability and density of ECM components. Figure adapted with permission Owen and Shoichet (2010); copyright 2010 Wiley Periodicals Inc.

Figure 2

Concept schematic for the spatial immobilization of growth factors that will preferentially and spatially differentiate retinal stem/progenitor cells to progeny of the retina in a layered structure.

Figure 3

Cell delivery with or without biomaterials to (a) the injured brain, (b) the injured spinal cord and (c) the subretinal space of the retina between the photoreceptors (rods and cones) and the retinal pigmented epithelium (RPE). (b) Image copyright (2005) by Michael Corrin.

Figure 4

Schematics of hydrogel-based drug delivery system to (a) the injured brain, and (b) the injured spinal cord. (a) The drug-containing hydrogel (HAMC) is placed on top of the cortex, permitting diffusion into the brain. The black arrows in the horizontal cross-section indicate diffusion in all directions. (b) Hydrogel injection into the space between the spinal cord and the dura mater, termed intrathecal space. Fast gelling hydrogels enable local release at the injection site. Figures adapted with permission from (a) Cooke et al (2011); copyright 2011 Elsevier. (b) Image copyright (2005) by Michael Corrin.