Current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury using polymer scaffolds

Abstract

This review highlights current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury. The concept of developing 3-dimensional polymer scaffolds for placement into a spinal cord transection model has recently been more extensively explored as a solution for restoring neurologic function after injury. Given the patient morbidity associated with respiratory compromise, the discrete tracts in the spinal cord conveying innervation for breathing represent an important and achievable therapeutic target. The aim is to derive new neuronal tissue from the surrounding, healthy cord that will be guided by the polymer implant through the injured area to make functional reconnections. A variety of naturally derived and synthetic biomaterial polymers have been developed for placement in the injured spinal cord. Axonal growth is supported by inherent properties of the selected polymer, the architecture of the scaffold, permissive microstructures such as pores, grooves or polymer fibres, and surface modifications to provide improved adherence and growth directionality. Structural support of axonal regeneration is combined with integrated polymeric and cellular delivery systems for therapeutic drugs and for neurotrophic molecules to regionalize growth of specific nerve populations.

The Development of a ɛ-Polycaprolactone Scaffold for Central Nervous System Repair

“…1,3,4 To overcome these specific problems, implantation of biocompatible oriented scaffolds of biodegradable polymers has been designed to promote aligned axonal outgrowth across the lesion. [5][6][7][8][9] Numerous potential substrates have been investigated for use in scaffold design, including (1) biocompatible hard degradable polymers, for example, e-polycaprolactone (PCL), 10 poly-L-lactide (PLLA), 11 poly(lactic-co-glycolic acid) (PLGA), and chitosan, or (2) hydrogels both naturally occurring, for example, agarose 12 and collagen, or synthetic, each possessing unique properties and characteristics. Polymers can also be blended with each other, to combine properties of their constituent materials including PCL/PGLA 13 and PCL/ chitosan.…”

Oriented, Multimeric Biointerfaces of the L1 Cell Adhesion Molecule: An Approach to Enhance Neuronal and Neural Stem Cell Functions on 2-D and 3-D Polymer Substrates

“…A variety of materials of natural and synthetic origin, have been previously shown to promote adhesion, proliferation, neurite extension, and neuronal differentiation of neural cells in vitro and in vivo [26][27][28]. Synthetic polymer-based biomaterial scaffolds have the added advantage of controlled chemistries and mechanical properties [29,30], while enabling display or release of neurotrophic factors [31,32].…”

“…Synthetic polymer-based biomaterial scaffolds have the added advantage of controlled chemistries and mechanical properties [29,30], while enabling display or release of neurotrophic factors [31,32]. Of the various scaffold configurations proposed to date [27,28,30], electrospun polymer substrates have exhibited excellent neurogenic properties, due to their high surface area and porosity, and fibrous ECM-like geometries [33,34].…”

Polymeric implant of methylprednisolone for spinal injury: preparation and characterization

“…Traumatic spinal cord injury is one of the most complex injuries to manage. Spinal injury leads to permanent disability, paraplegia, tetraplegia and over all decreased life expectancy [5][6][7]. There is no cure of spinal cord injury but efforts can be made to cope with the effects of primary and secondary spinal injury.…”