Transplantation of Nanostructured Composite Scaffolds Results in the Regeneration of Chronically Injured Spinal Cords

Abstract

The destruction and hollowing of entire tissue segments represent an insurmountable barrier to axonal regeneration and therapeutics in chronic spinal cord injury. To circumvent this problem, we engineered neural prosthetics, by assembling electrospun nanofibers and self-assembling peptides into composite guidance channels and transplanted them into the cysts of a postcontusive, chronic spinal cord injury rat model, also providing delivery of proregenerative cytokines. Six months later conspicuous cord reconstruction was observed. The cyst was replaced by newly formed tissue comprising neural and stromal cells. Nerve fibers were interspersed between and inside the guidance channels, spanning the lesion, amidst a well-developed vascular network, basal lamina, and myelin. This was accompanied by a significant improvement in the activity of ascending and descending motor pathways and the global locomotion score. Thus by engineering nanostructured matrices into neuroprosthetics, it is possible to recreate an anatomical, structural, and histological framework, which leads to the replacement of large, hollow tissue gaps in the chronically injured spinal cord, fostering axonal regeneration and neurological recovery.

An in vitro spinal cord injury model to screen neuroregenerative materials

“…The decision to use both coatings in this study was based on reports in the literature that suggest the attachment and extension of neuronal processes is enhanced on PDL-LAM coated surfaces, compared to PDL alone [56]. The extensive attachment of microglia to nanofibers bears resemblance to the activity of 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 microglia in vivo following transplantation of nanofiber scaffolds into SCI sites [57]. The observation that cells in the 3-D slices can distinguish between different surface coatings suggests that they are able to make sophisticated choices regarding material interactions, within a complex environment in vitro.…”

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

“…Further, in a subcutaneous model, none of the substrates induced cellular orientation parallel to the direction of the substrate topography. It is tempting to hypothesise that two-dimensional imprinted substrates are overwhelmed with body fluids and protein adsorption upon implantation, prohibiting favourable cell / material interaction at the substrate-tissue nano-biointerface and that three-dimensional fibrous constructs are more effective for directional neural [77][78][79], tendon [29,35,80], bone [81][82][83] and skin [84][85][86] neotissue formation and promote relatively enhanced cell growth, motility, matrix deposition and neotissue growth through the provision of a true three-dimensional environment.…”

Nano-Engineered Biomaterials for Tissue Regeneration: What Has Been Achieved So Far?

“…Top-Left: spinal cord injuries have numerous complications that are possibly overcome using hybrid scaffolds with growth factors. The implantation of this nanomaterial melds within the damaged region, providing tissue reconstruction and neural regeneration [adapted with permission from Gelain et al (2011)]. Top-Right: delivery platforms are garnering heightened attention, yet scaffolds can accelerate regeneration in specific cranial regions.…”