A Comparison Between Two Collagen Nerve Conduits and Nerve Autograft: A Rat Model of Motor Nerve Regeneration

Saltzman, Eliana B.; Villa, Jordan C.; Doty, Stephen B.; Feinberg, Joseph H.; Lee, Steve K.; Wolfe, Scott W.

doi:10.1016/j.jhsa.2018.10.008

Cited by 34 publications

(29 citation statements)

References 41 publications

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“…Types of NGCs, namely, synthetic (e.g., polyglycolic acid [PGA] and polycaprolactone [PCL]) and biological (e.g., veins, arteries, or collagen), have been studied as alternatives to autografts in short-gap models. However, the functional results of such conduits were not superior to those of autografts in longgap defects [10,[13][14][15][16][17]. Typically, conventional fabrication techniques can only result in the development of NGCs with simple architectures (e.g., straight hollow conduits) with limited choices of materials and dimensions [18].…”

Section: Introductionmentioning

confidence: 99%

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

Rodríguez-Sánchez

Pinto

Cartarozzi

et al. 2020

Preprint

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Background: Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration.Methods: 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL+MSC (NGC multi-functionalized with 106 canine AdMSC embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokines IL-6 and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve.Results: The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL+MSC group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair.Conclusions: 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach, support the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

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Section: Introductionmentioning

confidence: 99%

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

Rodríguez-Sánchez

Pinto

Cartarozzi

et al. 2020

Preprint

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“…Although the distance across which allografts and conduits induce axon regeneration can be increased by modifying them in various ways, none of those techniques can be used clinically. Therefore, despite their limitations, sensory nerve grafts remain the clinical "gold standard" for repairing peripheral nerves [69,70,166,[220][221][222][223]. The recovery of function across a 12-cm-long nerve gap of a 58-year-old patient, repaired 3.25 years post-trauma, suggests that functional recovery can be established, even when the values of all three injury parameters far exceed those where autografts are effective.…”

Section: Discussionmentioning

confidence: 99%

Restoration of Neurological Function Following Peripheral Nerve Trauma

Kuffler

Foy

2020

IJMS

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Following peripheral nerve trauma that damages a length of the nerve, recovery of function is generally limited. This is because no material tested for bridging nerve gaps promotes good axon regeneration across the gap under conditions associated with common nerve traumas. While many materials have been tested, sensory nerve grafts remain the clinical “gold standard” technique. This is despite the significant limitations in the conditions under which they restore function. Thus, they induce reliable and good recovery only for patients < 25 years old, when gaps are <2 cm in length, and when repairs are performed <2–3 months post trauma. Repairs performed when these values are larger result in a precipitous decrease in neurological recovery. Further, when patients have more than one parameter larger than these values, there is normally no functional recovery. Clinically, there has been little progress in developing new techniques that increase the level of functional recovery following peripheral nerve injury. This paper examines the efficacies and limitations of sensory nerve grafts and various other techniques used to induce functional neurological recovery, and how these might be improved to induce more extensive functional recovery. It also discusses preliminary data from the clinical application of a novel technique that restores neurological function across long nerve gaps, when repairs are performed at long times post-trauma, and in older patients, even under all three of these conditions. Thus, it appears that function can be restored under conditions where sensory nerve grafts are not effective.

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“…Promising results obtained using anisotropic topographical cues as luminal fillers can be seen in Figure 6. However, the incorporation of luminal fillers, regardless of their kind, is not always successful, as a recent study by Saltzman et al demonstrated (Saltzman et al, 2018). This study aimed to compare the performance of a PGA conduit containing collagen fibers within the conduit, a hollow collagen conduit, and a nerve autograft.…”

Section: Tissue Engineering and Regenerative Medicine Concepts For Pnrmentioning

confidence: 99%

Modern Trends for Peripheral Nerve Repair and Regeneration: Beyond the Hollow Nerve Guidance Conduit

Carvalho

Oliveira

Reis

2019

Front. Bioeng. Biotechnol.

213

210

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Peripheral nerve repair and regeneration remains among the greatest challenges in tissue engineering and regenerative medicine. Even though peripheral nerve injuries (PNIs) are capable of some degree of regeneration, frail recovery is seen even when the best microsurgical technique is applied. PNIs are known to be very incapacitating for the patient, due to the deprivation of motor and sensory abilities. Since there is no optimal solution for tackling this problem up to this day, the evolution in the field is constant, with innovative designs of advanced nerve guidance conduits (NGCs) being reported every day. As a basic concept, a NGC should act as a physical barrier from the external environment, concomitantly acting as physical guidance for the regenerative axons across the gap lesion. NGCs should also be able to retain the naturally released nerve growth factors secreted by the damaged nerve stumps, as well as reducing the invasion of scar tissue-forming fibroblasts to the injury site. Based on the neurobiological knowledge related to the events that succeed after a nerve injury, neuronal subsistence is subjected to the existence of an ideal environment of growth factors, hormones, cytokines, and extracellular matrix (ECM) factors. Therefore, it is known that multifunctional NGCs fabricated through combinatorial approaches are needed to improve the functional and clinical outcomes after PNIs. The present work overviews the current reports dealing with the several features that can be used to improve peripheral nerve regeneration (PNR), ranging from the simple use of hollow NGCs to tissue engineered intraluminal fillers, or to even more advanced strategies, comprising the molecular and gene therapies as well as cell-based therapies.

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A Comparison Between Two Collagen Nerve Conduits and Nerve Autograft: A Rat Model of Motor Nerve Regeneration

Cited by 34 publications

References 41 publications

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

Restoration of Neurological Function Following Peripheral Nerve Trauma

Modern Trends for Peripheral Nerve Repair and Regeneration: Beyond the Hollow Nerve Guidance Conduit

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