Electroactive Scaffolds to Improve Neural Stem Cell Therapy for Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is a serious condition caused by damage to the spinal cord through trauma or disease, often with permanent debilitating effects. Globally, the prevalence of SCI is estimated between 40 to 80 cases per million people per year. Patients with SCI can experience devastating health and socioeconomic consequences from paralysis, which is a loss of motor, sensory and autonomic nerve function below the level of the injury that often accompanies SCI. SCI carries a high mortality and increased risk of premature death due to secondary complications. The health, social and economic consequences of SCI are significant, and therefore elucidation of the complex molecular processes that occur in SCI and development of novel effective treatments is critical. Despite advances in medicine for the SCI patient such as surgery and anaesthesiology, imaging, rehabilitation and drug discovery, there have been no definitive findings toward complete functional neurologic recovery. However, the advent of neural stem cell therapy and the engineering of functionalized biomaterials to facilitate cell transplantation and promote regeneration of damaged spinal cord tissue presents a potential avenue to advance SCI research. This review will explore this emerging field and identify new lines of research.

A Strategy for Magnetic and Electric Stimulation to Enhance Proliferation and Differentiation of NPCs Seeded over PLA Electrospun Membranes

“…Both electric and magnetic stimulation have been applied as a non-invasive technique to modulate the excitability of the brain [ 82 , 83 , 84 ]. ES locally applied at the injured zone of the spinal cord has been widely studied, and some preclinical studies provide promising results regarding the promotion of functional recovery and regeneration [ 11 , 13 , 85 , 86 ]. The main inconvenience related to electrical stimulation arises in in vivo application, since electrodes are directly inserted into the stimulation site.…”

“…The main inconvenience related to electrical stimulation arises in in vivo application, since electrodes are directly inserted into the stimulation site. This invasiveness is a source of infection and can lead to a loss in stimulation efficacy and changes in the pH, among others [ 11 , 44 ]. Therefore, the strategy of inducing an electric current using a magnetic field allows one to apply not only electrical stimulation directly to the lesion site without using invasive electrodes but also a simultaneous application of two different types of stimulation widely used individually in clinics and broadly studied in research [ 8 , 40 , 52 , 78 , 82 , 83 ].…”

“…However, when applying NPC-based therapies, significant challenges still exist, such as poor cell engraftment and survival [ 7 ], as well as limited differentiation. In fact, the SCI lesion microenvironment causes NPCs to mostly differentiate into astrocytes, with minimal differentiation to neurons and oligodendrocytes, impending hence new neuronal circuits formation and remyelination [ 7 , 10 , 11 ]. Tissue engineering (TE) strategies have been gaining attention as an alternative approach in SCI injury treatment, with the aim of mimicking the native tissue both structurally and physiologically [ 12 ].…”

“…ES presents advantages, such as a precise application time and voltage magnitude control, but also limitations, such as the need of electrodes to apply the electrical stimulus, which make it an invasive technique when used in vivo [ 13 , 43 ]. Alternatively, minimally invasive methods that are based on the external delivery of ES to transplanted cells have been developed, but other off-target effects may appear due to their low spatial resolution [ 11 ]. Thus, designing a strategy to apply ES directly to the damaged area is a challenge.…”

Electroactive Biomaterials for Facilitating Bone Defect Repair under Pathological Conditions

“…(i.e., enhancement of angiogenesis, anti‐inflammatory, and anti‐bacterial properties). Indeed, electroactive scaffolds have also been reported to promote the regeneration of neural, [ 228 ] cardiac, [ 229 ] and skeletal muscle tissues. [ 230 ]…”