Neural regrowth induced by PLGA nerve conduits and neurotrophin‐3 in rats with complete spinal cord transection

Abstract

Biomaterials and neurotrophic factors represent two promising strategies for spinal cord injury repair. In this study, a combinatorial approach combining the PLGA nerve conduits and the recombinant human neurotrophin-3 (rhNT3) was utilized in a spinal cord injury animal model. After complete transection of the thoracic cord in rats, rhNT3 was administered as a single dose to the host cord caudal to a 2-mm conduit. Axonal regrowth was enhanced, as indicated by immunostaining and neurofilament-positive area measurement. Neural regrowth was further demonstrated via the retrograde tracing across the lesion. The animals implanted with the PLGA scaffold and rhNT3 exhibited significantly improved performance in BBB rating scale and grid walk tests. These observations suggest that PLGA nerve conduits combined with exogenous NT3 may serve as an alternative therapeutic approach for spinal cord injury repair.

Functionalized Collagen Scaffold Neutralizing the Myelin-Inhibitory Molecules Promoted Neurites Outgrowth in Vitro and Facilitated Spinal Cord Regeneration in Vivo

“…In our previously studies, we were focusing on the administration of neurotrophic factors alone or in combined with biomaterial scaffolds to the injured spinal cord, and those therapeutic strategies were identified to promote the survival and regeneration of many types of neurons. 17,23,[29][30][31][32] Therefore, the combined 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 application of neurotrophic factors was the next consideration. 2, although some long regenerated axons throughout the lesion area could be detected in group 5, the quantity might be not enough for locomotion recovery and the regenerated axons were likely to inappropriately form contacts with downstream target.…”

“…E15 rat dorsal root ganglia (DRG) cells were utilized for detecting the biological activity of the CBD-EphA4-LBD/CBD-PlexinB1-LBD. DRG cells were obtained and cultured as previously reported 23. DRG were isolated from E15 rat embryos and digested with 0.08% trypsin (Invitrogen, Carlsbad, CA) for 15 min.…”

Peripheral Nerve Grafts and Chondroitinase ABC Application Improves Functional Recovery After Complete Spinal Cord Transection

“…This creates an anatomical gap that axons are unable to cross. There have been several approaches used to bridge this anatomical gap, including poly(lactide-co-glycolide) (PLGA) scaffolds [9,10], Schwann cells [11], poly(ethylene glycol) hydrogels [12,13], agarose scaffolds [14,15], and peripheral nerve grafts (PNGs) [16][17][18][19][20][21][22]. PNGs are a living tissue containing several growth factors that have been shown to promote axonal growth, and cytokines that modulate inflammation [23,24].…”

Biodegradable Cell-Seeded Nanofiber Scaffolds for Neural Repair

“…Neurothrophin-3 (NT-3), a neurotrophic factor, has been found to enhance central nerve regeneration, particularly the corticospinal tracts [252,253]. Fan et al combined a PLGA conduit with NT-3 to treat a completely transected SCI using a rat model and observed a beneficial effect of this combination therapy in terms of neural regrowth and locomotor functional recovery [26]. Another neurotrophic factor, acidic fibroblast growth factor (a-FGF), a normal component of the spinal cord, has been demonstrated to promote functional recovery in SCI models, possibly due to its role in impeding or decreasing secondary injury and inducing neuroprotective protein factors [254][255][256][257].…”

“…However, using empty guidance channels alone hardly produces satisfactory results. Thus, when designing guidance channels made from either hydrogel [18,22,23] or polymer fibers, the following factors require consideration: they should be biodegradable, biocompatible, and permissive for cell growth; include neurostimulatory extracellular matrix (ECM) macromolecules (such as laminin-1 or laminin-1 fragments); include supportive cells, such as Schwann cells and stem cells; and include neurotrophic factors, such as neural growth factor (NGF-See Table 1 for abbreviations of materials in this paper) and brain-derived neurotrophic factor (BDNF) [24][25][26][27][28][29][30][31][32][33][34].…”