Long-Segment Nerve Allograft Regeneration in the Sheep Model:Experimental Study and Review of the Literature

Strasberg, Suzanne R.; Mackinnon, Susan E.; Genden, Eric M.; Bain, James R.; Purcell, Carrie M.; Hunter, Daniel A.; Hay, John B.

doi:10.1055/s-2007-1006625

Cited by 56 publications

(54 citation statements)

References 15 publications

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“…1,9,10,13,20 Other authors have failed to demonstrate axonal elongation after cryopreservation of longsegment allografts (8 cm in length). 26 The freeze-thawing process seems to leave perineurial and endoneurial connective tissues intact, effectively preventing infiltration by host lymphocytes as has been observed in fresh allografts and allowing nerve regeneration similar to that observed for autografts, as assessed by qualitative histology. 9 Moreover, experimental studies in rats and primates have demonstrated that immunosuppressive therapies (for example, with tacrolimus or cyclosporine A) maximize axonal regrowth and prevent rejection of the donor nerve 3,12,15,16 when used alone or when combined with allograft pretreatment.…”

Section: Discussionmentioning

confidence: 94%

Nerve regeneration across cryopreserved allografts from cadaveric donors: a novel approach for peripheral nerve reconstruction

Squintani

Bonetti

Paolin³

et al. 2013

JNS

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Object The use of allografts from cadaveric donors has attracted renewed interest in recent years, and pretreatment with cryopreservation and immunosuppression methods has been investigated to maximize axonal regrowth and minimize allograft rejection. The authors wanted to assess the outcome of treatments of brachial plexus stretch injuries with cryopreserved allografts from cadaveric donors in nonimmunosuppressed patients. Methods Ten patients with brachial plexus lesions were submitted to electromyography (EMG) testing 1 and 3 months after a traumatic event and 1 week before surgery to localize and identify the type of lesion. Intraoperative EMG recordings were performed for intraoperative monitoring to select the best surgical strategy, and postoperative EMG was used to follow up patients and determine surgical outcomes. If nerve action potentials (NAPs) were present intraoperatively, neurolysis was performed, whereas muscular/nerve neurotization was performed if NAPs were absent. Cryopreserved allografts obtained from selected cadaveric donors and provided by the tissue bank of Treviso were used for nerve reconstruction in patients who were not treated with immunosuppressive drugs. Results The surgical strategy was selected according to the type and site of the nerve lesion and on the basis of IOM results: 14 cryopreserved allografts were used for 7 muscular neurotizations and for 7 nerve neurotizations, and 5 neurolysis procedures were performed. All of the patients had regained motor function at the 1- and 2-year follow-ups. Conclusions Some variables may affect functional recovery after allograft surgery, and the outcome of peripheral nerve reconstruction is more favorable when patients are carefully evaluated and selected for the surgery. The authors demonstrated that using cryopreserved allografts from cadaveric donors is a valid surgical strategy to restore function of the damaged nerve without the need for any immunosuppressive treatments. This approach offers new perspectives on procedures for extensive reconstruction of brachial and lumbosacral plexuses.

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Section: Discussionmentioning

confidence: 94%

Nerve regeneration across cryopreserved allografts from cadaveric donors: a novel approach for peripheral nerve reconstruction

Squintani

Bonetti

Paolin³

et al. 2013

JNS

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“…3,[7][8][9][10][11][12][13][14] Autologous nerve grafts remain the gold standard for repairing longer nerve gaps, but are in limited supply, exhibit donor site morbidity, and may exhibit a size mismatch compared to the transected nerve. Nonautologous grafts can incorporate biological or synthetic components and have been designed with increasing complexity.…”

Section: Introductionmentioning

confidence: 99%

A Novel Internal Fixator Device for Peripheral Nerve Regeneration

Chuang

Wilson

Love

et al. 2013

Tissue Engineering Part C: Methods

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Recovery from peripheral nerve damage, especially for a transected nerve, is rarely complete, resulting in impaired motor function, sensory loss, and chronic pain with inappropriate autonomic responses that seriously impair quality of life. In consequence, strategies for enhancing peripheral nerve repair are of high clinical importance. Tension is a key determinant of neuronal growth and function. In vitro and in vivo experiments have shown that moderate levels of imposed tension (strain) can encourage axonal outgrowth; however, few strategies of peripheral nerve repair emphasize the mechanical environment of the injured nerve. Toward the development of more effective nerve regeneration strategies, we demonstrate the design, fabrication, and implementation of a novel, modular nerve-lengthening device, which allows the imposition of moderate tensile loads in parallel with existing scaffold-based tissue engineering strategies for nerve repair. This concept would enable nerve regeneration in two superposed regimes of nerve extension-traditional extension through axonal outgrowth into a scaffold and extension in intact regions of the proximal nerve, such as that occurring during growth or limb-lengthening. Self-sizing silicone nerve cuffs were fabricated to grip nerve stumps without slippage, and nerves were deformed by actuating a telescoping internal fixator. Poly(lactic co-glycolic) acid (PLGA) constructs mounted on the telescoping rods were apposed to the nerve stumps to guide axonal outgrowth. Neuronal cells were exposed to PLGA using direct contact and extract methods, and they exhibited no signs of cytotoxic effects in terms of cell morphology and viability. We confirmed the feasibility of implanting and actuating our device within a sciatic nerve gap and observed axonal outgrowth following device implantation. The successful fabrication and implementation of our device provides a novel method for examining mechanical influences on nerve regeneration.

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“…Strasberg et al studied an 80-mm nerve allograft in sheep, and Atchabahian et al examined an 80-mm nerve allograft in swine, but both studies showed that axonal regeneration across the untreated allograft was very poor. [18][19][20] Most studies have used short-gaps of <25 mm. [21][22][23][24][25][26][27] Few studies about longer gaps reported poor outcomes similar to allografts.…”

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confidence: 99%

Regeneration and repair of peripheral nerves with different biomaterials: Review

2010

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Peripheral nerve injury may cause gaps between the nerve stumps. Axonal proliferation in nerve conduits is limited to 10-15 mm. Most of the supportive research has been done on rat or mouse models which are different from humans. Herein we review autografts and biomaterials which are commonly used for nerve gap repair and their respective outcomes. Nerve autografting has been the first choice for repairing peripheral nerve gaps. However, it has been demonstrated experimentally that tissue engineered tubes can also permit lead to effective nerve repair over gaps longer than 4 cm repair that was previously thought to be restorable by means of nerve graft only. All of the discoveries in the nerve armamentarium are making their way into the clinic, where they are, showing great potential for improving both the extent and rate of functional recovery compared with alternative nerve guides.

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Long-Segment Nerve Allograft Regeneration in the Sheep Model:Experimental Study and Review of the Literature

Cited by 56 publications

References 15 publications

Nerve regeneration across cryopreserved allografts from cadaveric donors: a novel approach for peripheral nerve reconstruction

Nerve regeneration across cryopreserved allografts from cadaveric donors: a novel approach for peripheral nerve reconstruction

A Novel Internal Fixator Device for Peripheral Nerve Regeneration

Regeneration and repair of peripheral nerves with different biomaterials: Review

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