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

Hanna,

doi:10.4021/jnr209w

Cited by 5 publications

(8 citation statements)

References 31 publications

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“…It has also previously been shown that most of the regenerating axons after a spinal cord injury are unable to create useful connections (Lu et al, ). Research by others has shown amounts of axon growth into the PNGs and functional recovery after SCI similar to those in the group that was treated only with PNGs in this study (Houle et al, ; Tom et al, ; Cote et al, 2011; Hanna et al, ). Even though there are more axons in the grafts that had sutures releasing NT‐3, the axons may not be making functional connections after their regrowth.…”

Section: Discussionsupporting

confidence: 76%

“…It is possible that the axons are growing into the graft before scar formation but are unable to grow out the other side because of the dense glial scar that has accumulated over time. To alleviate this, chondroitinase ABC could be released in conjunction with NT‐3 to digest the chondroitin sulfate proteoglycans, creating a more permissible environment for axon growth (Bradbury et al, ; Caggiano et al, ; Barritt et al, ; H. Lee et al, ; Hanna et al, ). It has also previously been shown that most of the regenerating axons after a spinal cord injury are unable to create useful connections (Lu et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…To alleviate this, chondroitinase ABC could be released in conjunction with NT-3 to digest the chondroitin sulfate proteoglycans, creating a more permissible environment for axon growth (Bradbury et al, 2002;Caggiano et al, 2005;Barritt et al, 2006;H. Lee et al, 2010;Hanna et al, 2013). It has also previously been shown that most of the regenerating axons after a spinal cord injury are unable to create useful connections (Lu et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…One of the more promising SCI treatments is the use of peripheral nerve grafts (PNGs) as scaffolds for axonal growth to bridge the lesion (Aguayo et al, ; Tadie et al, ; Houle et al, ; Tom and Houle, ; Tom et al, ; Cote et al, ; Alilain et al, ; Hanna et al, ). PNGs are particularly advantageous because they are a functional, living tissue in which the original axons degenerate, leaving behind a hollow “tunnel” of Schwann cells.…”

mentioning

confidence: 99%

“…Contract grant sponsor: Bryon Riesch Paralysis Foundation; Contract grant number: 133-PRJ57YV 2011; Hanna et al, 2013). PNGs are particularly advantageous because they are a functional, living tissue in which the original axons degenerate, leaving behind a hollow "tunnel" of Schwann cells.…”

mentioning

confidence: 99%

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Sustained release of neurotrophin‐3 via calcium phosphate‐coated sutures promotes axonal regeneration after spinal cord injury

Hanna

Thompson

Hellenbrand

et al. 2016

J of Neuroscience Research

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Because of the dynamics of spinal cord injury (SCI), the optimal treatment will almost certainly be a combination approach to control the environment and promote axonal growth. This study uses peripheral nerve grafts (PNGs) as scaffolds for axonal growth while delivering neurotrophin-3 (NT-3) via calcium phosphate (CaP) coatings on surgical sutures. CaP coating was grown on sutures, and NT-3 binding and release were characterized in vitro. Then, the NT-3-loaded sutures were tested in a complete SCI model. Rats were analyzed for functional improvement and axonal growth into the grafts. The CaP-coated sutures exhibited a burst release of NT-3, followed by a sustained release for at least 20 days. Functionally, the rats with PNGs + NT-3-loaded sutures and the rats treated with PNGs scored significantly higher than controls on day 56 postoperatively. However, functional scores in rats treated with PNGs + NT-3-loaded suture were not significantly different from those of rats treated with PNGs alone. Cholera toxin subunit B (CTB) labeling rostral to the graft was not observed in any controls, but CTB labeling rostral to the graft was observed in almost all rats that had had a PNG. Neurofilament labeling on transverse sections of the graft revealed that the rats treated with the NT-3-loaded sutures had significantly more axons per graft than rats treated with an NT-3 injection and rats without NT-3. These data demonstrate that PNGs serve as scaffolds for axonal growth after SCI and that CaP-coated sutures can efficiently release NT-3 to increase axonal regeneration. © 2016 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Sustained release of neurotrophin‐3 via calcium phosphate‐coated sutures promotes axonal regeneration after spinal cord injury

Hanna

Thompson

Hellenbrand

et al. 2016

J of Neuroscience Research

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Single-dose mRNA therapy via biomaterial-mediated sequestration of overexpressed proteins

et al. 2020

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Nonviral mRNA delivery is an attractive therapeutic gene delivery strategy, as it achieves efficient protein overexpression in vivo and has a desirable safety profile. However, mRNA’s short cytoplasmic half-life limits its utility to therapeutic applications amenable to repeated dosing or short-term overexpression. Here, we describe a biomaterial that enables a durable in vivo response to a single mRNA dose via an “overexpress and sequester” mechanism, whereby mRNA-transfected cells locally overexpress a growth factor that is then sequestered within the biomaterial to sustain the biologic response over time. In a murine diabetic wound model, this strategy demonstrated improved wound healing compared to delivery of a single mRNA dose alone or recombinant protein. In addition, codelivery of anti-inflammatory proteins using this biomaterial eliminated the need for mRNA chemical modification for in vivo therapeutic efficacy. The results support an approach that may be broadly applicable for single-dose delivery of mRNA without chemical modification.

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Sustained delivery of chABC improves functional recovery after a spine injury

et al. 2022

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Introduction Chondroitinase ABC (chABC) is an enzyme could improve regeneration and thereby improving functional recovery of spinal cord injury (SCI) in rodent models. Degradation of the active enzyme and diffusion away from the lesion are the causes of using hydrogels as a scaffold to deliver the chABC into the lesion site. In this meta-analysis, we investigated the effects of chABC embedded in a scaffold or hydrogel on the functional recovery after SCI. Method Databases were searched based on keywords related to chABC and spinal cord injury (SCI). Primary and secondary screening was performed to narrow down study objectives and inclusion criteria, and finally the data were included in the meta-analysis. The standard mean difference of the score of the functional recovery that measured by Basso, Beattie, Bresnahan (BBB) test after SCI was used to analyze the results of the reported studies. Subgroup analysis was performed based on SCI model, severity of SCI, transplantation type, and the follow-up time. Quality control of articles was also specified. Results The results showed that embedding chABC within the scaffold increased significantly the efficiency of functional recovery after SCI in animal models (SMD = 1.95; 95% CI 0.71–3.2; p = 0.002) in 9 studies. SCI model, severity of SCI, injury location, transplantation type, and the follow-up time did not affect the overall results and in all cases scaffold effect could not be ignored. However, due to the small number of studies, this result is not conclusive and more studies are needed. Conclusion The results could pave the way for the use of chABC embedded in the scaffold for the treatment of SCI and show that this method of administration is superior to chABC injection alone.

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

Cited by 5 publications

References 31 publications

Sustained release of neurotrophin‐3 via calcium phosphate‐coated sutures promotes axonal regeneration after spinal cord injury

Sustained release of neurotrophin‐3 via calcium phosphate‐coated sutures promotes axonal regeneration after spinal cord injury

Single-dose mRNA therapy via biomaterial-mediated sequestration of overexpressed proteins

Sustained delivery of chABC improves functional recovery after a spine injury

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