Bioengineered Strategies for Spinal Cord Repair

Abstract

This article reviews bioengineered strategies for spinal cord repair using tissue engineered scaffolds and drug delivery systems. The pathophysiology of spinal cord injury (SCI) is multifactorial and multiphasic, and therefore, it is likely that effective treatments will require combinations of strategies such as neuroprotection to counteract secondary injury, provision of scaffolds to replace lost tissue, and methods to enhance axonal regrowth, synaptic plasticity, and inhibition of astrocytosis. Biomaterials have major advantages for spinal cord repair because of their structural and chemical versatility. To date, various degradable or non-degradable biomaterial polymers have been tested as guidance channels or delivery systems for cellular and non-cellular neuroprotective or neuroregenerative agents in experimental SCI. There is promise that bioengineering technology utilizing cellular treatment strategies, including Schwann cells, olfactory ensheathing glia, or neural stem cells, can promote repair of the injured spinal cord. This review is divided into three parts: (1) degradable and non-degradable biomaterials; (2) device design; and (3) combination strategies with scaffolds. We will show that bioengineering combinations of cellular and non-cellular strategies have enhanced the potential for experimental SCI repair, although further pre-clinical work is required before this technology can be translated to humans.

An in vitro spinal cord injury model to screen neuroregenerative materials

“…'Combinatorial' neural tissue engineering strategies have been suggested to be essential to promote various aspects of neural regeneration (such as nerve fiber regeneration, suppression of scar formation and immune responses, promotion of blood vessel growth) within the complex, multi-faceted pathology of SCI [36][37][38][39][40]. Such synergistic approaches have the potential to regenerate the injured spinal cord with varying degrees of efficacy, but none have been successfully translated into the clinic [41].…”

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].…”

Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury

“…The pathophysiology of spinal cord injury is a highly complex process that involves primary and second-ary injuries, and the underlying mechanisms have not been definitively established [5][6][7] . Therapeutic interventions to treat SCI remain limited, and various strategies have been tested in animal models [8][9][10] . Previous studies have shown that transplantation of several different types of precursor/stem cells promoted axonal regeneration and functional recovery in animal models of SCI [11][12][13][14][15][16] .…”

“…Tissue engineering with biomaterial scaffolds has brought novel possibilities for the treatment of spinal cord injury [9,16] . Several types of synthetic biodegradable polymers have been tested, including poly (glycolic acid) (PGA), poly (L-lactic acid) (PLLA), poly (ε-caprolactone) (PCL) and poly (lactic-coglycolic acid) (PLGA).…”