Biomaterials for spinal cord repair

Abstract

Spinal cord injury (SCi) results in permanent loss of function leading to often devastating personal, economic and social problems. A contributing factor to the permanence of SCi is that damaged axons do not regenerate, which prevents the re-establishment of axonal circuits involved in function. Many groups are working to develop treatments that address the lack of axon regeneration after SCi. The emergence of biomaterials for regeneration and increased collaboration between engineers, basic and translational scientists, and clinicians hold promise for the development of effective therapies for SCi. A plethora of biomaterials is available and has been tested in various models of SCi. Considering the clinical relevance of contusion injuries, we primarily focus on polymers that meet the specific criteria for addressing this type of injury. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Designing materials to address the specific needs of the damaged central nervous system is crucial and possible with current technology. Here, we review the most prominent materials, their optimal characteristics, and their potential roles in repairing and regenerating damaged axons following SCi.Keywords: spinal cord injury; axon regeneration; biodegradable materials; extracellular matrix proteins; functional recovery; growth factor; guidance; injury and repair; spinal motor neuron IntroductionSpinal cord injury (SCi) causes loss of neurons and axons resulting in motor and sensory function impairments. There are thousands of new cases of SCi in the world annually [1,2] occurring often in young adults. The lack of endogenous repair and the significant costs to the individual, family and society [1] are important motivations behind the continuing efforts to develop effective therapies. Promoting axonal regeneration is considered a potential repair strategy because it could lead to recovery of axonal circuits involved in motor and/or sensory function [3] .The central nervous system (CNS) neurons are intrinsically capable of some regeneration of damaged axons [4] but their attempts after SCi are frustrated by structural and chemical obstructions in the damaged nervous tissue [5] . Spinal cord repair approaches typically lead to small functional gains. one feature that most of these approaches have in common is a poor axonal regeneration response, suggesting that promoting axonal regeneration, including synapse formation, is essential to achieve substantial functional repair after SCi. if so, it is rational to anticipate that effective spinal cord therapies will need to include interventions addressing the axon growth-inhibition that leads to the poor axonal growth responses. As introduced above, axonal regeneration is considered an important repair mechanism for the injured spinal cord. Therefore, this review focuses on materials that have shown most promise to elicit an axonal regeneration response to foster functional restoration after ...

Electrospun Fibers for Drug Delivery after Spinal Cord Injury and the Effects of Drug Incorporation on Fiber Properties

“…The sections presented subsequently are not meant to be comprehensive reviews but a general overview. For comprehensive reviews focusing on specific categories of biomaterials and providing a more thorough analysis of different biomaterial strategies under development for repair of the injured spinal cord refer to [Haggerty, and Oudega, 2013; Krishna et al, 2013; Macaya, and Spector, 2012; Pakulska et al, 2012; Perale et al, 2011; Schaub et al, 2015a; Straley et al, 2010; Tsintou et al, 2015]. The next sections present different biomaterial approaches either as being non-directional (unable to direct the extension of regenerating axons) or directional, and the results of such approaches when employed within an animal model of SCI.…”

One-year clinical study of NeuroRegen scaffold implantation following scar resection in complete chronic spinal cord injury patients

“…Biomaterial scaffolds can be used to bridge the lesion site in patients with SCI, providing a structural platform to facilitate axonal growth and also a vehicle to deliver stem cells and functional biomolecules to favorably reconstruct the microenvironment at the injury site (Haggerty and Oudega, 2013). A linearly ordered collagen scaffold termed NeuroRegen scaffold was found to induce axonal growth along collagen fibers and inhibit scar formation after implantation in animal studies.…”

Cationic, amphiphilic copolymer micelles as nucleic acid carriers for enhanced transfection in rat spinal cord

“…In addition to paralysis and loss of sensory function below the level of the lesion, SCI may also lead to chronic pain, spasticity, respiratory impairment, loss of bowel or bladder control, and sexual dysfunction. A wide range of therapeutic strategies are being developed to promote axonal regeneration, including cell transplantation[1], neurotrophin delivery[2], removal of growth inhibition[3–7], manipulation of intracellular signaling[8, 9], immune modulation [10], and use of bridging scaffolds for axonal guidance [11–15]. However, there is no clinically effective therapy currently available.…”