Dextran-based tube-guides for the regeneration of the rat sciatic nerve after neurotmesis injury

Pinho, Ana C.; Branquinho, Mariana; Alvites, Rui; Fonseca, A. C.; Caseiro, Ana Rita; Pedrosa, Sílvia Santos; Luís, Ana Lúcia; Pires, Isabel; Prada, Justina; Muratori, Luísa; Ronchi, Giulia; Geuna, Stefano; Santos, José G.; Maurício, Ana Colette; Serra, Arménio C.; Coelho, Jorge Fernando Jordão

doi:10.1039/c9bm00901a

Cited by 13 publications

(9 citation statements)

References 77 publications

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“…Finally, the collected segments were kept immersed in the fixing solution for 6-8 h, after which they were washed abundantly in a washing solution consisting of 1.5% saccharose in 0.1 M Sorensen phosphate buffer at pH 7.4, being kept immersed in this solution until analysis. Histomorphometric analysis was performed according to a protocol previously used [68], and the parameters total number of fibers (N), fiber density (N/mm 2 ), axon diameter (d, µ), fiber diameter (D, µ), myelin thickness (M, µ) and cross-sectional area (mm 2 ) were considered, in addition to the ratios d/D (g-ratio), M/d, D/d.…”

Section: Neurological Evaluationmentioning

confidence: 99%

Establishment of a Sheep Model for Hind Limb Peripheral Nerve Injury: Common Peroneal Nerve

Alvites

Branquinho

Sousa

et al. 2021

IJMS

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Thousands of people worldwide suffer from peripheral nerve injuries and must deal daily with the resulting physiological and functional deficits. Recent advances in this field are still insufficient to guarantee adequate outcomes, and the development of new and compelling therapeutic options require the use of valid preclinical models that effectively replicate the characteristics and challenges associated with these injuries in humans. In this study, we established a sheep model for common peroneal nerve injuries that can be applied in preclinical research with the advantages associated with the use of large animal models. The anatomy of the common peroneal nerve and topographically related nerves, the functional consequences of its injury and a neurological examination directed at this nerve have been described. Furthermore, the surgical protocol for accessing the common peroneal nerve, the induction of different types of nerve damage and the application of possible therapeutic options were described. Finally, a preliminary morphological and stereological study was carried out to establish control values for the healthy common peroneal nerves regarding this animal model and to identify preliminary differences between therapeutic methods. This study allowed to define the described lateral incision as the best to access the common peroneal nerve, besides establishing 12 and 24 weeks as the minimum periods to study lesions of axonotmesis and neurotmesis, respectively, in this specie. The post-mortem evaluation of the harvested nerves allowed to register stereological values for healthy common peroneal nerves to be used as controls in future studies, and to establish preliminary values associated with the therapeutic performance of the different applied options, although limited by a small sample size, thus requiring further validation studies. Finally, this study demonstrated that the sheep is a valid model of peripheral nerve injury to be used in pre-clinical and translational works and to evaluate the efficacy and safety of nerve injury therapeutic options before its clinical application in humans and veterinary patients.

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Section: Neurological Evaluationmentioning

confidence: 99%

Establishment of a Sheep Model for Hind Limb Peripheral Nerve Injury: Common Peroneal Nerve

Alvites

Branquinho

Sousa

et al. 2021

IJMS

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“…The surgical procedures applied in this work were based on the techniques previously used and described [ 17 , 25 ]. The specificities and adaptations are described below.…”

Section: Methodsmentioning

confidence: 99%

Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration

et al. 2022

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Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.

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“…Humane end points were followed in agreement with the OECD Guidelines (2000). The in vivo biocompatibility assessment was performed in adult male Sasco Sprague-Dawley rats (Charles River, Barcelona, Spain) weighing 250–300 g, as described in previous works [ 55 , 58 ]. Animals were housed with controlled temperature and humidity and 12–12 h light/dark cycles.…”

Section: Methodsmentioning

confidence: 99%

In Vitro and In Vivo Characterization of PLLA-316L Stainless Steel Electromechanical Devices for Bone Tissue Engineering—A Preliminary Study

Branquinho

Ferreira

Alvites

et al. 2021

IJMS

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Bone injuries represent a major social and financial impairment, commonly requiring surgical intervention due to a limited healing capacity of the tissue, particularly regarding critical-sized defects and non-union fractures. Regenerative medicine with the application of bone implants has been developing in the past decades towards the manufacturing of appropriate devices. This work intended to evaluate medical 316L stainless steel (SS)-based devices covered by a polymer poly (L-lactic acid) (PLLA) coating for bone lesion mechanical and functional support. SS316L devices were subjected to a previously described silanization process, following a three-layer PLLA film coating. Devices were further characterized and evaluated towards their cytocompatibility and osteogenic potential using human dental pulp stem cells, and biocompatibility via subcutaneous implantation in a rat animal model. Results demonstrated PLLA-SS316L devices to present superior in vitro and in vivo outcomes and suggested the PLLA coating to provide osteo-inductive properties to the device. Overall, this work represents a preliminary study on PLLA-SS316L devices’ potential towards bone tissue regenerative techniques, showing promising outcomes for bone lesion support.

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Dextran-based tube-guides for the regeneration of the rat sciatic nerve after neurotmesis injury

Abstract: Nerve tube-guides based on dextran and poly(ε-caprolactone) were successfully used in the recovery of a neurotmesis injury in rat model.

Cited by 13 publications

References 77 publications

Establishment of a Sheep Model for Hind Limb Peripheral Nerve Injury: Common Peroneal Nerve

Establishment of a Sheep Model for Hind Limb Peripheral Nerve Injury: Common Peroneal Nerve

Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration

In Vitro and In Vivo Characterization of PLLA-316L Stainless Steel Electromechanical Devices for Bone Tissue Engineering—A Preliminary Study

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