The Effect of Chondroitinase on Nerve Regeneration Following Composite Tissue Allotransplantation

Tuffaha, Sami H.; Quigley, Michael A.; Ng, T. W.; Gorantla, Vijay S.; Shores, Jaimie T.; Pulikkottil, Benson J.; Shestak, Christopher; Brandacher, Gerald; Lee, W.P. Andrew

doi:10.1016/j.jhsa.2011.06.007

Cited by 19 publications

(14 citation statements)

References 29 publications

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“…We are currently using high-frequency ultrasound to monitor regeneration after hand transplant surgery and peripheral nerve injury, and to determine the efficacy of experimental drug therapies [8]. Accurate identification of changes in nerve anatomy such as edema, myelin debris, or fascicular/axonal changes could help objectively diagnose nerve injury or monitor nerve regeneration after trauma or surgery.…”

Section: Results In 2d With Ultrasoundmentioning

confidence: 99%

Descending Variance Graphs for Segmenting Neurological Structures

Stetten

Wong

Shivaprabhu

et al. 2013

2013 International Workshop on Pattern Recognition in Neuroimaging

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Abstract-We present a novel and relatively simple method for clustering pixels into homogeneous patches using a directed graph of edges between neighboring pixels. For a 2D image, the mean and variance of image intensity is computed within a circular region centered at each pixel. Each pixel stores its circle's mean and variance, and forms the node in a graph, with possible edges to its 4 immediate neighbors. If at least one of those neighbors has a lower variance than itself, a directed edge is formed, pointing to the neighbor with the lowest variance. Local minima in variance thus form the roots of disjoint trees, representing patches of relative homogeneity. The method works in n-dimensions and requires only a single parameter: the radius of the circular (spherical, or hyperspherical) regions used to compute variance around each pixel. Setting the intensity of all pixels within a given patch to the mean at its root pixel significantly reduces image noise while preserving anatomical structure, including location of boundaries. The patches may themselves be clustered using techniques that would be computationally too expensive if applied to the raw pixels. We demonstrate such clustering to identify fascicles in the median nerve in high-resolution 2D ultrasound images, as well as white matter hyperintensities in 3D magnetic resonance images.

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Section: Results In 2d With Ultrasoundmentioning

confidence: 99%

Descending Variance Graphs for Segmenting Neurological Structures

Stetten

Wong

Shivaprabhu

et al. 2013

2013 International Workshop on Pattern Recognition in Neuroimaging

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“…We have been able to stabilize and release ChABC from our nerve guides and extend the therapeutic window of the enzyme. The large burst of active ChABC that, based on the in vitro data, was released in the first 24 h after implantation may have provided a similar effect to the single doses of enzyme previously shown to positively affect outcomes after nerve transection (Tuffaha et al ., ). The fact that minimal active ChABC was recovered after 24 h could be due to a combination of thermal inactivation of the enzyme, or active enzyme remaining bound within the silk–trehalose film.…”

Section: Discussionmentioning

confidence: 97%

“…The mechanism is through cleavage of chondroitin sulphate proteoglycans, major inhibitory regulators of axonal regeneration after nerve regeneration. Interestingly, single injections of ChABC at the site of peripheral nerve repair have shown benefit in a hind limb vascularized composite allotransplantation model, leading to increased axonal number and fibre density across the anastomosis site (Tuffaha et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Delivery of chondroitinase ABC and glial cell line-derived neurotrophic factor from silk fibroin conduits enhances peripheral nerve regeneration

Sivak

White

Bliley

et al. 2014

J Tissue Eng Regen Med

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Nerve conduits are a proven strategy for guiding axon regrowth following injury. This study compares degradable silk-trehalose films containing chondroitinase ABC (ChABC) and/or glial cell line-derived neurotrophic factor (GDNF) loaded within a silk fibroin-based nerve conduit in a rat sciatic nerve defect model. Four groups of silk conduits were prepared, with the following silk-trehalose films inserted into the conduit: (a) empty; (b) 1 µg GDNF; (3) 2 U ChABC; and (4) 1 µg GDNF/2 U ChABC. Drug release studies demonstrated 20% recovery of GDNF and ChABC at 6 weeks and 24 h, respectively. Six conduits of each type were implanted into 15 mm sciatic nerve defects in Lewis rats; conduits were explanted for histological analysis at 6 weeks. Tissues stained with Schwann cell S-100 antibody demonstrated an increased density of cells in both GDNF- and ChABC-treated groups compared to empty control conduits (p < 0.05). Conduits loaded with GDNF and ChABC also demonstrated higher levels of neuron-specific PGP 9.5 protein when compared to controls (p < 0.05). In this study we demonstrated a method to enhance Schwann cell migration and proliferation and also foster axonal regeneration when repairing peripheral nerve gap defects. Silk fibroin-based nerve conduits possess favourable mechanical and degradative properties and are further enhanced when loaded with ChABC and GDNF. Copyright © 2014 John Wiley & Sons, Ltd.

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“…63 Additionally, chondroitinase treatment has shown to improve nerve regeneration in both a rat model of nerve transection and crush injury. 64 Chondroitinase has been shown to improve nerve regeneration in a rat orthotopic hind limb transplant model, with animals receiving the enzyme demonstrating statistically greater total number of fibers and nerve density compared with controls. 65 These early animal studies demonstrate the promise of potentially using this enzyme in VCA to improve nerve regeneration by augmenting the extracellular matrix surrounding the nerve transection site.…”

Section: Growth Hormonementioning

confidence: 99%

Advances in peripheral nerve regeneration as it relates to VCA

Suchyta

Sabbagh

Morsy

et al. 2016

Vascularized Composite Allotransplantation

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Vascularized composite allotransplant (VCA) offers functional, social, and quality of life improvements for patients who have exhausted traditional reconstructive options. Unlike solid organ transplant, VCA success is not only based upon the quality of perfusion and level of immunosuppression, but also on the success of nerve regeneration within the transplanted part. This paper will summarize the present state of peripheral nerve regeneration in the context of VCA and will explore the latest research advances that will affect the future of the field. These advances offer promising future strategies to improve patient outcomes in VCA.

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The Effect of Chondroitinase on Nerve Regeneration Following Composite Tissue Allotransplantation

Cited by 19 publications

References 29 publications

Descending Variance Graphs for Segmenting Neurological Structures

Descending Variance Graphs for Segmenting Neurological Structures

Delivery of chondroitinase ABC and glial cell line-derived neurotrophic factor from silk fibroin conduits enhances peripheral nerve regeneration

Advances in peripheral nerve regeneration as it relates to VCA

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