Biomaterials for Local, Controlled Drug Delivery to the Injured Spinal Cord

Abstract

Affecting approximately 17,000 new people each year, spinal cord injury (SCI) is a devastating injury that leads to permanent paraplegia or tetraplegia. Current pharmacological approaches are limited in their ability to ameliorate this injury pathophysiology, as many are not delivered locally, for a sustained duration, or at the correct injury time point. With this review, we aim to communicate the importance of combinatorial biomaterial and pharmacological approaches that target certain aspects of the dynamically changing pathophysiology of SCI. After reviewing the pathophysiology timeline, we present experimental biomaterial approaches to provide local sustained doses of drug. In this review, we present studies using a variety of biomaterials, including hydrogels, particles, and fibers/conduits for drug delivery. Subsequently, we discuss how each may be manipulated to optimize drug release during a specific time frame following SCI. Developing polymer biomaterials that can effectively release drug to target specific aspects of SCI pathophysiology will result in more efficacious approaches leading to better regeneration and recovery following SCI.

Regenerative Therapies for Spinal Cord Injury

“…4). 6,132 In addition, they can support cell survival of delivered cells in situ, 44,50 as discussed later in this review, and recruit migrating endogenous cells, such as Schwann cells 121 and stem cells, 111,112,140 that can support regeneration. To avoid additional complexities associated with the use of cells, the use of acellular biomaterials for supporting spinal cord regeneration and remodeling after injury has been important to investigate.…”

“…[126][127][128][129][130] Biomaterials are used to mechanically stabilize the injury site and provide an environment for interactions with host cells, physically fill SCI-associated cavities, reconstituting ECM, and bridging the injury to guide axonal growth across the gap. 70,101,112,121,[131][132][133][134][135] To guide axonal regeneration, several biomaterial architectures have been investigated, including channels, 86,[136][137][138] fibers, 139 scaffolds, and magnetic microgels. 58 Biomaterials for the treatment of SCI can also be used for the delivery of therapeutic agents and cells (Fig.…”

“…At later stages the use of fibers and conduits may be better for achieving guided neural regeneration. 132 However, it would be ideal to design a system that could be implanted acutely and remain for months to both guide regeneration and prevent chronic inflammation.…”

Carbonyl scavengers as pharmacotherapies in degenerative disease: Hydralazine repurposing and challenges in clinical translation

“…Tissue deterioration during the secondary phase can take weeks or months to peak, finally conferring a dysfunctional tissue environment featuring apoptosis, demyelination, glial scarring and Wallerian degeneration. Awareness that secondary processes strongly influence overall impairment in SCI has inspired a broad effort to evaluate various pharmaceutical and biotechnology-based interventions that attempt to attenuate these pathophysiological events [42].…”

“…In prior work, Shi and associates successfully developed a novel hydralazine delivery system involving polyethylene glycolfunctionalised mesoporous silica nanoparticles which performed well during in vitro efficacy bioassays in PC12 cells [91]. The ongoing development of hydrogels, electrospun fibres and other technologies that permit localised drug delivery to damaged cords may further assist the development of successful localised delivery methods for hydralazine [92,93].…”