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

Sivak, Wesley N.; White, James D.; Bliley, Jacqueline M.; Tien, Lee W.; Liao, Han-Tsung; Kaplan, David L.; Marra, Kacey G.

doi:10.1002/term.1970

Cited by 32 publications

(22 citation statements)

References 44 publications

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“…Enhancing the nerve conduit or scaffold itself with neurotrophic factors, such as glial-derived neurotrophic factor (GDNF), has proven to be an effective way to recruit Schwann cells and promote axonal regeneration. 46,47 Similarly, microspheres enhanced with nerve growth factors have been used to deliver growth factors to regenerating nerves with promising results. 48,49 Studies delivering insulin-like growth factor-1 (IGF-1) into the repair site show improved physical and functional recovery not only in young but also in aged animals.…”

Section: Future Directionsmentioning

confidence: 99%

Nerve Repair with Nerve Conduits: Problems, Solutions, and Future Directions

et al. 2018

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Nerve conduits are becoming increasingly popular for the repair of peripheral nerve injuries. Their ease of application and lack of donor site morbidity make them an attractive option for nerve repair in many situations. Today, there are many different conduits to choose in different sizes and materials, giving the reconstructive surgeon many options for any given clinical problem. However, to properly utilize these unique reconstructive tools, the peripheral nerve surgeon must be familiar not only with their standard indications but also with their functional limitations. In this review, the authors identify the common applications of nerve conduits, expected results, and shortcomings of current techniques. Furthermore, future directions for nerve conduit use are identified.

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Section: Future Directionsmentioning

confidence: 99%

Nerve Repair with Nerve Conduits: Problems, Solutions, and Future Directions

et al. 2018

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“…Engineered bionic conduit showed promising in vivo results [132]. Research has also reported the development of silk fibroin conduits loaded with nerve growth factors [133][134][135][136][137][138]. Despite the promising results, no silk conduit has yet been FDA approved.…”

Section: N-fibroinmentioning

confidence: 99%

Scaffolds for Peripheral Nerve Regeneration, the Importance of In Vitro and In Vivo Studies for the Development of Cell-Based Therapies and Biomaterials: State of the Art

Pedrosa¹,

Caseiro²,

Santos³

et al. 2017

Scaffolds in Tissue Engineering - Materials, Technologies and Clinical Applications

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Human adult peripheral nerve injuries are a high incidence clinical problem that greatly affects patients' quality of life. Although peripheral nervous system has intrinsic regenerative capacity, this occurs in an incomplete or poorly functional manner. When a nerve fiber loses its continuity with consequent damage of the basal lamina tubes, axon spontaneous regeneration is disorganized and mismatched. These phenomena translate in an inadequate nerve functional recovery and consequent musculoskeletal incapacity. Nerve grafts still remain the gold standard in peripheral injuries treatment. However, this approach contains its disadvantages such as the necessity of primary surgery to harvest the autografts, loss of a functional nerve, donor site morbidity and longer surgery procedures. Therefore, biomaterials and tissue engineering can provide efficient resources and alternatives to nerve injury repair not only by the development of biocompatible structures but also, introducing neurotrophic factors and cellular systems to stimulate optimum clinical outcome. In this chapter, a comprehensive state-of-the art picture of tissue-engineered nerve grafts scaffolds, their application in nerve regeneration along with latest advances in peripheral nerve repair and future perspectives will be discussed, including our own large experience in this field of knowledge.

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“…This makes it a very strong candidate for treatment of human SCI. Moreover, ChABC also has the potential for wider therapeutic application, since it has recently been shown to improve outcome following peripheral nerve injury [10], and to promote cardiac sympathetic nerve regeneration following experimental myocardial infarction [11]. Additionally, there are an increasing number of studies describing beneficial results of the enzyme in experimental models of stroke [12,13].…”

Section: Introductionmentioning

confidence: 99%

Targeting chondroitinase ABC to axons enhances the ability of chondroitinase to promote neurite outgrowth and sprouting

et al. 2020

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Background There is currently no effective treatment for promoting regeneration of injured nerves in patients who have sustained injury to the central nervous system such as spinal cord injury. Chondroitinase ABC is an enzyme, which promotes neurite outgrowth and regeneration. It has shown considerable promise as a therapy for these conditions. The aim of the study is to determine if targeting chondroitinase ABC expression to the neuronal axon can further enhance its ability to promote axon outgrowth. Long-distance axon regeneration has not yet been achieved, and would be a significant step in attaining functional recovery following spinal cord injury. Methodology/Principal findings To investigate this, neuronal cultures were transfected with constructs encoding axon-targeted chondroitinase, non-targeted chondroitinase or GFP, and the effects on neuron outgrowth and sprouting determined on substrates either permissive or inhibitory to neuron regeneration. The mechanisms underlying the observed effects were also explored. Targeting chondroitinase to the neuronal axon markedly enhances its ability to promote neurite outgrowth. The increase in neurite length is associated with an upregulation of β-integrin staining at the axonal cell surface. Staining for phosphofocal adhesion kinase, is also increased, indicating that the β-integrins are in an activated state. Expression of chondroitinase within the neurons also resulted in a decrease in expression of PTEN and RhoA, molecules which present a block to neurite outgrowth, thus identifying two of the pathways by which ChABC promotes neurite outgrowth. Conclusions / Significance The novel finding that targeting ChABC to the axon significantly enhances its ability to promote neurite extension, suggests that this may be an effective way of promoting long

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

Cited by 32 publications

References 44 publications

Nerve Repair with Nerve Conduits: Problems, Solutions, and Future Directions

Nerve Repair with Nerve Conduits: Problems, Solutions, and Future Directions

Scaffolds for Peripheral Nerve Regeneration, the Importance of In Vitro and In Vivo Studies for the Development of Cell-Based Therapies and Biomaterials: State of the Art

Targeting chondroitinase ABC to axons enhances the ability of chondroitinase to promote neurite outgrowth and sprouting

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