The effects of gradients of nerve growth factor immobilized PCLA scaffolds on neurite outgrowth in vitro and peripheral nerve regeneration in rats

Tang, Shuo; Zhu, Jixiang; Xu, Yangbin; Xiang, Andy Peng; Jiang, Manli

doi:10.1016/j.biomaterials.2013.05.080

Cited by 138 publications

(142 citation statements)

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“…32,40 Thus, for in vivo peripheral nerve regeneration, we explored the efficacy of SIS-and PCLANGCs in bridging a 15-mm sciatic nerve defect gap without any cells and/or nerve growth factors. NGC implantation surgery was well tolerated in all PNI models.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

Shim

Kwon

Lee

et al. 2015

Tissue Engineering Part A

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The present study employed nerve guidance conduits (NGCs) only, which were made of small intestine submucosa (SIS) and poly(caprolactone-co-lactide) (PCLA) to promote nerve regeneration in a peripheral nerve injury (PNI) model with nerve defects of 15 mm. The SIS-and PCLA-NGCs were easily prepared by rolling of a SIS sheet and a bioplotter using PCLA, respectively. The prepared SIS-and PCLA-NGCs fulfilled the general requirement for use as artificial peripheral NGCs such as easy fabrication, reproducibility for mass production, suturability, sterilizability, wettability, and proper mechanical properties to resist collapsing when applied to in vivo implantation. The SIS-and PCLA-NGCs appeared to be well integrated into the host sciatic nerve without causing dislocations and serious inflammation. All NGCs stably maintained their NGC shape for 8 weeks without collapsing, which matched well with the nerve regeneration rate. Staining of the NGCs in the longitudinal direction showed that the regenerated nerves grew successfully from the SIS-and PCLA-NGCs through the sciatic nerve-injured gap and connected from the proximal to distal direction along the NGC axis. SIS-NGCs exhibited a higher nerve regeneration rate than PCLANGCs. Collectively, our results indicate that SIS-and PCLA-NGCs induced nerve regeneration in a PNI model, a finding that has significant implications in the future with regard to the feasibility of clinical nerve regeneration with SIS-and PCLA-NGCs prepared through an easy fabrication method using promising biomaterials.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

Shim

Kwon

Lee

et al. 2015

Tissue Engineering Part A

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“…Natural regeneration may occur over short nerve gaps (1-2 mm). Direct end-to-end nerve suture is performed for nerve gaps of <5 mm [3,4]. Tensionless suturing is required for successful nerve repair.…”

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confidence: 99%

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth

Sugimura‐Wakayama

Katagiri

Osugi

et al. 2015

Stem Cells and Development

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Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.

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“…Like substrate-bound factors, when these are distributed in a uniform concentration around a neuron in vitro, its neurites extend randomly in all directions [76]. However, when a concentration gradient of these factors is presented to a neurite growth cone by releasing them from the tip of a micropipette, the growth cone turns and moves up the concentration gradient [15,76,79,80]. Similarly, in vivo, as neurotrophic factors diffuse away from a length of denervated nerve or denervated muscle fibers, a diffusible concentration gradient of these factors is formed [9,76].…”

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confidence: 99%

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

Kuffler¹

2015

Int J Neurorehabilitation Eng

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Repairing Peripheral Nerves following Traumas Nerve crushWithin several days of crushing a peripheral nerve, the injured axons begin to regenerate through their distal pathway until they reach their original targets with which they restore neurological function. The larger the number of axons that regenerate through the distal nerve, the greater the extent of neurological recovery [1][2][3]. The number of axons that regenerate, and thus neurological recovery, is influenced by the physiological state of the distal denervated nerve pathway [4][5][6][7].Following a peripheral nerve crush, the injured axons begin to regenerate within 2 days of injury [8]. They may regenerate to their targets through their original pathway in association with and promoted by its Schwann cells, the neurotrophic factors they release, and the Schwann cell extracellular matrix [1,4,[9][10][11][12][13][14]. Thus, the distal nerve provides a simple means for promoting and directing the regenerating axons to their original targets [15][16][17][18]. However, when a nerve has a gap, the gap must be bridged with a material that is permissive to and promotes axon regeneration across the entire gap to reach the distal nerve stump, through which the axons must then be able to regenerate.The Schwann cells in the denervated distal nerve release neurotrophic factors that promote axon regeneration, but also release extracellular matrix components that promote and inhibit axon regeneration [19][20][21][22][23][24][25][26]. Thus, regeneration through the distal nerve is a balance of the influences of factors that both promote and inhibit regeneration. If the Schwann cells are present, such as after a simple nerve crush, virtually 100% of the axons regenerate and they innervate all the denervated synaptic sites. If the Schwann cells within the distal nerve pathway are killed, leaving only the extracellular matrix intact, the number of axons that regenerates to their targets decreases by 94%. This is because the factors required to trigger the regenerating axons to branch at extracellular matrix branch points are missing, axons do not branch, and therefore each axon reinnervates only a single denervated muscle fiber. Thus, Schwann cells along the distal nerve pathway and a AbstractFollowing a peripheral nerve crush, or when a peripheral the nerve is transected and the nerve stumps anastomosed, neurological recovery is generally excellent. This is because the axons merely have to regenerate through the distal portion of the nerve through the existing extracellular matrix of the denervated Schwann cells that direct and promote them to their distant denervated motor and sensory targets. However, when a length of a peripheral nerve is destroyed, and anastomosis is not possible, the standard surgical repair technique is to graft a length/s of autologous sensory nerve into the gap. Neurological recovery is generally good if the nerve gap is <2 cm in length, the repair is performed <4 months post trauma, and the patients are <25 years of age. Because the nerve ...

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The effects of gradients of nerve growth factor immobilized PCLA scaffolds on neurite outgrowth in vitro and peripheral nerve regeneration in rats

Cited by 138 publications

References 39 publications

Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

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