Local FK506 delivery at the direct nerve repair site improves nerve regeneration

Davis, Brett; Hilgart, David; Erickson, Sierra; Labroo, Pratima; Burton, Joshua N.; Sant, Himanshu; Shea, Jill E.; Gale, Bruce K.; Agarwal, Jay

doi:10.1002/mus.26656

Cited by 19 publications

(13 citation statements)

References 48 publications

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“…Fibrin glue proves its effectiveness in peripheral nerve repair by reducing the inflammatory response and improving axon regeneration. Also, Davis et al showed that the continuous release of local tacrolimus (FK506) to repair site cloud actively inhibits neuroma formation ( 57 ). They used 3D-printing technology to create a polyethylene Y-shape conduit loop, where the nerve will be connected instead of direct connection to autografts.…”

Section: Preventionmentioning

confidence: 99%

Traumatic neuromas of peripheral nerves: Diagnosis, management and future perspectives

et al. 2023

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Traumatic neuromas are infrequent in clinical settings but are prevalent following trauma or surgery. A traumatic neuroma is not a true malignancy, rather, it is a hyperplastic, reparative nerve reaction after injury and typically manifests as a nodular mass. The most common clinical manifestations include painful hypersensitivity and the presence of a trigger point that causes neuralgic pain, which could seriously decrease the living standards of patients. While various studies are conducted aiming to improve current diagnosis and management strategies via the induction of emerging imaging tools and surgical or conservative treatment. However, researchers and clinicians have yet to reach a consensus regarding traumatic neuromas. In this review, we aim to start with the possible underlying mechanisms of traumatic neuromas, elaborate on the diagnosis, treatment, and prevention schemes, and discuss the current experiment models and advances in research for the future management of traumatic neuromas.

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Section: Preventionmentioning

confidence: 99%

Traumatic neuromas of peripheral nerves: Diagnosis, management and future perspectives

et al. 2023

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“…For this reason, systemic administration is not a mainstay in the current treatment of nerve injuries. However, the potential to provide local FK506 via drug‐delivery devices, as well as administration of immunophilin ligands with no immunosuppressive effects, could minimize these concerns while capitalizing on its neuroregenerative effects 15,17–19 . Further, sub‐immunosuppressive doses of FK506 have also shown some beneficial effect in promoting nerve regeneration, 20 although maximum potency is achieved with immunosuppressive doses 21…”

Section: Introductionmentioning

confidence: 99%

“…However, the potential to provide local FK506 via drug-delivery devices, as well as administration of immunophilin ligands with no immunosuppressive effects, could minimize these concerns while capitalizing on its neuroregenerative effects. 15,[17][18][19] Further, sub-immunosuppressive doses of FK506 have also shown some beneficial effect in promoting nerve regeneration, 20 although maximum potency is achieved with immunosuppressive doses. 21 Electrical stimulation (E-stim) is another neuroenhancing therapeutic that has been shown to positively affect nerve regeneration.…”

Section: Introductionmentioning

confidence: 99%

Electrical stimulation or tacrolimus (FK506) alone enhances nerve regeneration and recovery after nerve surgery, while dual use reduces variance and combines strengths of each in promoting enhanced outcomes

et al. 2022

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Introduction/Aims Repaired nerve injuries can fail to achieve functional recovery. Therapeutic options beyond surgery, such as systemic tacrolimus (FK506) and electrical stimulation (E‐stim), can improve recovery. We tested whether dual administration of FK506 and E‐stim enhances regeneration and recovery more than either therapeutic alone. Methods Rats were randomized to four groups: E‐stim, FK506, FK506 + E‐stim, and repair alone. All groups underwent tibial nerve transection and repair. Two sets of animals were created to measure outcomes of early nerve regeneration using nerve histology (n = 36) and functional recovery (n = 42) (21‐ and 42‐day endpoints, respectively). Functional recovery was measured by behavioral analyses (walking track and grid walk) and, at the endpoint, muscle mass and force. Results Dual E‐stim and FK506 administration produced histomorphometric measurements of nerve regeneration no different than either therapeutic alone. All treatments were superior to repair alone (FK506, P < .0001; E‐stim, P < .05; FK506 + E‐stim, P < .05). The E‐stim and FK506 + E‐stim groups had improved behavioral recovery compared with repair alone (at 6 weeks: E‐stim, P < .05; FK506 + E‐stim, P < .01). The FK506 group had improved recovery based on walking‐track analysis (at 6 weeks: P < .001) and muscle force and mass (P < .05). The concurrent use of both therapies ensured earlier functional recovery and decreased variability in functional outcomes compared with either therapy alone, suggesting a moderate benefit. Discussion Dual administration of FK506 and E‐stim showed minimal additive effects to further improve regeneration or recovery compared with either therapy alone. The data suggest the combination of FK506 and E‐stim appears to combine the relative strengths of each therapeutic.

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“…Many such experimental therapies are growth factors including glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor (FGF), and brain-derived neurotrophic growth factor ( Fex Svenningsen and Kanje, 1996 ; Lee et al, 2007 ; Gordon, 2009 ). Tacrolimus (FK506), delivered either systemically or locally, has also shown promise in a number of studies ( Konofaos and Terzis, 2013 ; Davis et al, 2019 ; Tajdaran et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor-1: A Promising Therapeutic Target for Peripheral Nerve Injury

Slavin

Sarhane

Guionneau

et al. 2021

Front. Bioeng. Biotechnol.

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Patients who sustain peripheral nerve injuries (PNIs) are often left with debilitating sensory and motor loss. Presently, there is a lack of clinically available therapeutics that can be given as an adjunct to surgical repair to enhance the regenerative process. Insulin-like growth factor-1 (IGF-1) represents a promising therapeutic target to meet this need, given its well-described trophic and anti-apoptotic effects on neurons, Schwann cells (SCs), and myocytes. Here, we review the literature regarding the therapeutic potential of IGF-1 in PNI. We appraised the literature for the various approaches of IGF-1 administration with the aim of identifying which are the most promising in offering a pathway toward clinical application. We also sought to determine the optimal reported dosage ranges for the various delivery approaches that have been investigated.

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Local FK506 delivery at the direct nerve repair site improves nerve regeneration

Cited by 19 publications

References 48 publications

Traumatic neuromas of peripheral nerves: Diagnosis, management and future perspectives

Traumatic neuromas of peripheral nerves: Diagnosis, management and future perspectives

Electrical stimulation or tacrolimus (FK506) alone enhances nerve regeneration and recovery after nerve surgery, while dual use reduces variance and combines strengths of each in promoting enhanced outcomes

Insulin-Like Growth Factor-1: A Promising Therapeutic Target for Peripheral Nerve Injury

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