Hydrogels in Spinal Cord Injury Repair Strategies

Abstract

)Mi.To. Technology s.r.l., Licensing Department, Viale Vittorio Veneto 2/a, 20124 Milan, Italy T raumatic spinal cord injury (SCI) is an irreversible dramatic event that can incapacitate victims for life. 1À4 Although the incidence is relatively low, the often severe disability that follows and the fact that the victims are often young people, the consequences for the patient is severe and the impact on societal costs is significant. The injury is the result of a primary event due to contusive, compressive, or stretch injury, 1,2,5 followed by the so-called "secondary injury", commonly considered the main cause of the post-traumatic neural degeneration of the cord itself. 6À8 Functional deficits of SCI are caused by different temporal events: spinal cord compression and/or contusion lead to ischemic events that limit both oxygen and glucose contribution to the tissue, with concomitant neuronal cell death, axon damage, and demyelination. 5 Subsequently, glial activation, release of inflammatory factors and cytokines, and scar formation that impedes axons to regrow 8,9 aggravate the progression of the damage.SCI research is following two principal paths. 6,9À11 The first one, already applied in human cases, is based on systemic pharmacological treatments in order to contain side effects (ischemia, free radical release, and inflammation) using neuroprotective drugs (such as corticosteroids) 12À14 and to promote self-regeneration using stimulating factors. 15 The second one relies on tissue engineering 16À18 approaches such as the direct injection of stem cells 19À21 and active agents (drugs, antibodies, and peptides) into the affected area with the aim to bridge the lesion, possibly after removal of the glial scar or reducing endogenous neurite-inhibitory molecules. 22,23 Direct injection of in vitro cultured cells or drugs is the most common choice, but keeping transplanted cells in the lesion area is often desired as transplanted cells readily leave the zone of injection if not confined by any support. To achieve this, a new potential approach is to combine material science with tissue engineering as has been proposed and developed. 16,24À26 In Figure 1 are presented classic tissue engineering approaches as the combination of scaffolds with cells and active agents in order to replace damaged parts of biological tissues. 17,18 In the wide field of biomaterials, increased attention is given to polymers, not only to fabricate three-dimensional scaffolds but also to develop injectable systems for tissue engineering. 26À34 One of the most suitable classes of compounds for these purposes is surely represented by hydrogels. 16,28,31,35À39 These polymers are typically soft and elastic due to their thermodynamic compatibility with water. 16,33,36,40 They can be designed as temporary structures having desired geometry and physical, chemical, and mechanical properties adequate for implantation into chosen target tissue. 6,41À43The aim of this Review is to show the different types of hydrogels used as scaffolds for...

Chimeric Self-assembling Nanofiber Containing Bone Marrow Homing Peptide’s Motif Induces Motor Neuron Recovery in Animal Model of Chronic Spinal Cord Injury; an In Vitro and In Vivo Investigation

“…One of the most critical inhibitors in recovery of SCI is inflammation, and overcoming this obstacle would be an important step in treatment of disorder. By regards to the fact that implantation of performed scaffolds induces further damage and decreases recovery potential at the site injury in spinal cord due to low cell viability, infiltration of immune cells, poor graft integration, and void space, implantation of an injectable hydrogelbased scaffold holds great promise with minimum invasion to the injury site [1][2][3][4].…”

Leveraging “Raw Materials” as Building Blocks and Bioactive Signals in Regenerative Medicine

“…73 In addition, HA interacts with specific protein receptors on the surface of cells, such as CD44 and RHAMM, to modulate cell adhesion, proliferation, motility, and other signaling cascades. 74 For these reasons, HA has been utilized in recent tissue engineering strategies for skin, 50 89,91 Crosslinking can function to increase mechanical strength, while also prolonging degradation of HA. 65 Zhang et al 67 engineered a hydrogel scaffold by thermal crosslinking for cartilage tissue engineering that comprised solely of components found in the ECM of cartilage tissue using bovine collagen type I, HA, and CS (Table 3).…”

Self-Assembling Peptide Nanofiber Containing Long Motif of Laminin Induces Neural Differentiation, Tubulin Polymerization, and Neurogenesis: In Vitro, Ex Vivo, and In Vivo Studies

“…Since inflammation in the site of SCI inhibits its recovery, scientists started to design injectable hydrogel-based scaffolds with lesser invasion to the injury site to overcome this obstacle. The drawbacks related to implantation of preformed scaffold in soft tissues are poor graft integration, not filling of void spaces, low cell viability, and infiltration of immune cells that decrement recovery capacity and induces further damage at the site of SCI [1][2][3][4].…”