The incorporation of growth factor and chondroitinase ABC into an electrospun scaffold to promote axon regrowth following spinal cord injury.

Spinal cord injury results in tissue necrosis in and around the lesion site, commonly leading to the formation of a fluid-filled cyst. This pathological end point represents a physical gap that impedes axonal regeneration. To overcome the obstacle of the cavity, we have explored the extent to which axonal substrates can be bioengineered through electrospinning, a process that uses an electrical field to produce fine fibres of synthetic or biological molecules. Recently, we demonstrated the potential of electrospinning to generate an aligned matrix that can influence the directionality and growth of axons. Here, we show that this matrix can be supplemented with nerve growth factor and chondroitinase ABC to provide trophic support and neutralize glial-derived inhibitory proteins. Moreover, we show how air-gap electrospinning can be used to generate a cylindrical matrix that matches the shape of the cord. Upon implantation in a completely transected rat spinal cord, matrices supplemented with NGF and chondroitinase ABC promote significant functional recovery. An examination of these matrices post-implantation shows that electrospun aligned monofilaments induce a more robust cellular infiltration than unaligned monofilaments. Further, a vascular network is generated in these matrices, with some endothelial cells using the electrospun fibres as a growth substrate. The presence of axons within these implanted matrices demonstrates that they facilitate axon regeneration following spinal cord injury. Collectively, these results demonstrate the potential of electrospinning to generate an aligned substrate that can provide trophic support, directional guidance cues and regeneration-inhibitory neutralizing compounds to regenerating axons following spinal cord injury. Copyright © 2016 John Wiley & Sons, Ltd.

FTY720 reduces inflammation and promotes functional recovery after spinal cord injury.

A robust and complex inflammatory cascade is known to be a prominent component of secondary injury following spinal cord injury (SCI). Specifically, the concept of trauma-induced autoimmunity has linked the lymphocyte population with neural tissue injury and neurologic deficit. FTY720, a sphingosine receptor modulator that sequesters lymphocytes in secondary lymphoid organs, has been shown to be effective in the treatment of a variety of experimental autoimmune disorders. Accordingly, by reducing lymphocyte infiltration into the spinal cord following SCI, this novel immunomodulator may enhance tissue preservation and functional recovery. In the present study, a moderate to severe contusion SCI was simulated in adult Long-Evans hooded rats. Using flow cytometry we showed that daily FTY720 treatment dramatically reduced T-cell infiltration into the SCI lesion site at 4 and 7 days post-injury, while other inflammatory cell populations were relatively unaltered. To assess functional recovery, three groups of injured animals (treated, vehicle, and injury only) were evaluated weekly for hindlimb recovery. Animals in the treated group consistently exhibited higher functional scores than animals in the control groups after 2 weeks post-injury. This finding was associated with a greater degree of white matter sparing at the lesion epicenter when cords were later sectioned and stained. Furthermore, treated animals were found to exhibit improved bladder function and a reduced incidence of hemorrhagic cystitis compared to control counterparts. Collectively these results demonstrate the neuroprotective potential of FTY720 treatment after experimental SCI.

Titanium miniplates or stainless steel wire for cranial fixation: a prospective randomized comparison.

OBJECT: The authors designed a study to compare low-profile titanium miniplate fixation to that in which stainless steel wire is used. METHODS: Before undergoing craniotomy, 40 patients gave informed consent and were randomized to receive either wire or miniplate fixation. After dural closure, bone flap fixation was timed. The bone flap was measured for inward or outward offset and mobility to manual pressure on its margin. Three months postoperatively the bone flap margins were graded for appearance or palpation of an offset and for the presence of burr hole depressions. Twenty-four patients were randomized to receive miniplate fixation and 16 to receive stainless steel wire fixation. The time required for wire fixation was approximately 40% longer than that for miniplates (11.8 +/- 5.1 minutes compared with 8.3 +/- 5 minutes, p = 0.02). The offset of bone flaps after wire fixation was significantly greater than that with miniplates (1.6 +/- 1 mm compared with 0.3 +/- 0.6 mm, p < 0.001), as was the mobility of the bone flap on digital pressure (1.2 +/- 0.9 mm compared with 0.2 +/- 0.5 mm, p < 0.001). At the 3-month follow-up review, two of 12 patients had suboptimal results after wire fixation, whereas none of 14 patients had suboptimal results after miniplate fixation. When dichotomized for excellent or less-than-excellent postoperative results, the data were significantly better for patients who underwent miniplate fixation (p < 0.05). CONCLUSIONS: Titanium miniplate cranial fixation provides more accurate and rigid reapproximation of the bone edges, with results that are significantly better on close inspection or palpation. The additional cost of miniplate fixation may thus be justified in many cases.