Polyethylene glycol in spinal cord injury repair: a critical review

Abstract

Polyethylene glycol (PEG) is a synthetic biocompatible polymer with many useful properties for developing therapeutics to treat spinal cord injury. Direct application of PEG as a fusogen to the injury site can repair cell membranes, mitigate oxidative stress, and promote axonal regeneration to restore motor function. PEG can be covalently or noncovalently conjugated to proteins, peptides, and nanoparticles to limit their clearance by the reticuloendothelial system, reduce their immunogenicity, and facilitate crossing the blood–brain barrier. Cross-linking PEG produces hydrogels that can act as delivery vehicles for bioactive molecules including growth factors and cells such as bone marrow stromal cells, which can modulate the inflammatory response and support neural tissue regeneration. PEG hydrogels can be cross-linked in vitro or delivered as an injectable formulation that can gel in situ at the site of injury. Chemical and mechanical properties of PEG hydrogels are tunable and must be optimized for creating the most favorable delivery environment. Peptides mimicking extracellular matrix protein such as laminin and n-cadherin can be incorporated into PEG hydrogels to promote neural differentiation and axonal extensions. Different hydrogel cross-linking densities and stiffness will also affect the differentiation process. PEG hydrogels with a gradient of peptide concentrations or Young’s modulus have been developed to systematically study these factors. This review will describe these and other recent advancements of PEG in the field of spinal cord injury in greater detail.

Bridging the gap: Spinal cord fusion as a treatment of chronic spinal cord injury

“…[26,74,77,105,112,117] When the transection is partial, recovery is possible: 66% of 450 patients with stab wounds could eventually walk without or with only minimal help in one series and over half of 217 patients returned to their former occupation, usually within 6 months of the injury, in another. [4,84] Brown-Sequard types of lesion (i.e., hemisections) also recover: for instance, two patients with cervical hemisection recovered walking at 10 and 2 years[35] and another recovered almost completely at 3 years. [33] If the section is >50% (of a hemisection), results are similar to a complete section: in a representative patient, whose spinal cord was almost completely divided at C7/T1, only sensory disturbance was slightly improved at 4 months after the injury.…”

Cell and Tissue Instructive Materials for Central Nervous System Repair

“…[52] These results can be due to a better integration of PEG biomatrix in the lesion site, and due to its physical properties, such as porosity and high water content that favors its application as a CTIM in SCI strategies. [53] Using PEG microspheres as an intermediate phase to control the porosity of the structure, tubes, and bridges were assembled in a composite hydrogel with fibrin (added to provide structural stability). In a thoracic hemisection injury mice model, the implantation of these structures increased the axonal density at rostral and caudal regions, as well as the alignment of these fibers in the lesion site.…”

Current Developments in Antioxidant Therapies for Spinal Cord Injury

“…Polyethylene glycol (PEG) is a surfactant that due to its hydrophilic nature allows the fusion and fluidity of the cell membrane that reduces the oxidative Current Developments in Antioxidant Therapies for Spinal Cord Injury DOI: http://dx.doi.org /10.5772/intechopen.85424 effects of the secondary stage and that during the acute phase of SCI, it may inhibit nerve fiber degeneration and create a favorable microenvironment for the regeneration of nerve filaments that can stimulate angiogenesis and reduce glial scar, promoting the regeneration of axonal guidance and motor recovery. PEG has been widely used as a scaffold for a large variety of molecules in treatment for SCI [132][133][134][135][136], while the SOD enzyme has antioxidant properties, as mentioned previously. The combination of SOD with PEG (PEG-SOD) allows an increase of the enzyme intracellularly and its antioxidant activity, and it may have an important role in vascular relaxation by reducing the concentration of O2 •− and limiting the LP [132].…”