Spinal cord injury repair by implantation of structured hyaluronic acid scaffold with PLGA microspheres in the rat

Abstract

In order to create an optimal microenvironment for neural regeneration in the lesion area after spinal cord injury (SCI), we fabricated a novel scaffold composed of a hyaluronic acid (HA) hydrogel with a longitudinal multi-tubular conformation. The scaffold was modified by binding with an anti-Nogo receptor antibody (antiNgR) and mixed further with poly(lactic-co-glycolic acid) (PLGA) microspheres containing brain-derived neurotrophic factor and vascular endothelial growth factor (HA+PLGA). In the rat, after implantation of this composite into an injured area created by a dorsal hemisection at T9-10 of the spinal cord, favorable effects were seen with regard to the promotion of spinal repair, including excellent integration of the implants with host tissue, inhibition of inflammation, and gliosis. In particular, large numbers of new blood vessels and regenerated nerve fibers were found within and around the implants. Simultaneously, the implanted rats exhibited improved locomotor recovery. Thus, this novel composite material might provide a suitable microenvironment for neural regeneration following SCI.

Control-released basic fibroblast growth factor-loaded poly-lactic-co-glycolic acid microspheres promote sciatic nerve regeneration in rats

“…Angiogenesis, which occurs during the early stages of traumatic brain injury, stroke and nerve injury, is associated with nerve recovery as sufficient blood supply is a key factor in the creation of an optimal microenvironment for neural regeneration (24,25). Increased angiogenesis during the acute phase following nerve injury is able to stimulate endogenous recovery mechanisms and promote functional recovery (24).…”

“…Guiding of regenerated axons to grow longitudinally through the lesion area is necessary for repairing nerve injury, as linear growth of axons should maintain the native organization and potentially increase the probability of improving functional recovery of the injured nerve (25). Ma et al (27) recently confirmed that scaffolds with longitudinal channels are able to stimulate and guide linear axonal growth following peripheral nerve injury in rats.…”

“…Ma et al (27) recently confirmed that scaffolds with longitudinal channels are able to stimulate and guide linear axonal growth following peripheral nerve injury in rats. Various materials have been synthesized with tubular structures or guidance channels to adapt to the anatomy of the peripheral nerve, such as PLGA scaffold (31,32), agarose scaffold (33), collagen scaffold (2) and hyaluronic acid hydrogel scaffold (25). However, this tubular arrangement may be irregular and difficult to reproduce.…”

Neurotrophic Factors Used to Treat Spinal Cord Injury

“…NT-3 has also been administered in a range of studies in association with scaffolds of various types, composed of collagen Houweling, van Asseldonk, et al, 1998;Li et al, 2016;Yao et al, 2013), fibrin (Guo et al, 2007;Taylor, Jones, et al, 2006;Wilems et al, 2015), matrigel (Bamber et al, 2001), hyaluronic acid/PLGA (Wen et al, 2015), chitosan , or hydrogels (Piantino et al, 2006;Tsai et al, 2006). Improved outcomes using a combination of NT-3 gradients, peripheral conditioning lesions, and stromal cell grafts up to 15 months after SCI have also been reported (Kadoya et al, 2009).…”

Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats

“…PLGA is a biodegradable and biocompatible complex [15, 16] that has been utilized as a tissue engineering complex in a number of studies [17-20]. They tend to provide a better cell growth milieu in the conveyance of exogenous cells into the lesion site, promoting and supporting axonal growth towards the damaged neural cells or tissues [21].…”