Book Description

Spinal cord injury occurs when the cord is subjected to physical trauma. Because spinal cord tissue exhibits limited regenerative capacity, injuries result in significant loss of motor, sensory, and autonomic function. In the hours to weeks following initial trauma, secondary injury mechanisms are triggered, exacerbating tissue damage. Because these mechanisms occur at delayed timepoints, they can theoretically can be targeted by therapeutic interventions. Although a wide range of molecules have been shown to attenuate secondary injury mechanisms in animal models of SCI, clinical translation of these strategies has been slow, in part due to difficulty in safely and effectively achieving therapeutic concentrations of the indicated molecules in injured spinal cord tissue. Biomaterials-based drug delivery systems offer unique opportunities to safely administer drugs to the injured spinal cord while avoiding any deleterious side effects associated with systemic drug administration. In the first part of this thesis, a novel drug delivery system was developed, characterized, and optimized to target endogenous progenitor differentiation with the goal of replacing oligodendrocytes lost during SCI progression. The drug delivery system was shown to safely provide local delivery of the thyroid hormone T3, a known inducer of oligodendrocyte differentiation that cannot be safely administered systemically at therapeutic doses. Local delivery of T3 stimulated oligodendrocyte differentiation, resulting in increased numbers of newly generated oligodendrocytes and improved myelination following SCI. In the second part of this thesis, drug delivery systems were developed to target the inflammatory response following SCI. Delivery systems were based on novel drug-loaded microparticles, which were extensively characterized to reveal mechanisms of formation and drug release, and shown to provide sustained release of a synthetic PEGylated peptide as well as a small molecule drug. These strategies highlight the promise of biomaterials-based drug delivery to expand the researcher's toolkit, allowing for the use of previously infeasible drugs, and to facilitate the translation of therapeutic strategies from neuroscience laboratories to viable clinical treatments.