Efficient bridging of 20 mm rat sciatic nerve lesions with a longitudinally micro-structured collagen scaffold

Bozkurt, Ahmet; Böcker, Arne; Tank, Julian; Altinova, Haktan; Deumens, Ronald; Dabhi, Christina; Tolba, René; Weis, Joachim; Brook, Gary; Pallua, Norbert; Neerven, Sabien G. A. van

doi:10.1016/j.biomaterials.2015.10.009

Cited by 69 publications

(63 citation statements)

References 58 publications

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“…This strategy using bone mesenchymal stem cells and chondroitinase ABC was shown to significantly improve nerve regeneration, as well as myelination, including myelin thickness (Wang et al, 2012). In a recent study, autologous nerve grafts and micro-structured collagen scaffolds seeded with Schwann cells were directly compared for their ability to support nerve repair (Bozkurt et al, 2016). This report indicates that the addition of Schwann cells to the engineered scaffold benefitted myelination, although nerve regeneration was just as efficient without the glia.…”

Section: Biomaterials Engineeringmentioning

confidence: 99%

Promoting peripheral myelin repair

Zhou

Notterpek

2016

Experimental Neurology

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Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves.

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Section: Biomaterials Engineeringmentioning

confidence: 99%

Promoting peripheral myelin repair

Zhou

Notterpek

2016

Experimental Neurology

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“…However, these methods do not lead to functional recovery13678. Furthermore, ANG has several significant shortcomings, including the additional trauma induced by harvest of the donor nerve, limited donor sites and lengths of available grafts, impaired target organ function in the donor area, and 3-dimensional structural incompatibility between the recipient and donor nerves91011.…”

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confidence: 99%

“…Efforts have been made to promote PN repair using biomaterials; however, such studies have achieved limited functional recovery113334. In this study, we test a novel combinatorial repair strategy for promoting functional nerve regeneration following complete transection of the RLN in rats.…”

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confidence: 99%

Functional regeneration of the transected recurrent laryngeal nerve using a collagen scaffold loaded with laminin and laminin-binding BDNF and GDNF

Wang

Yuan

Chen

et al. 2016

Sci Rep

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Recurrent laryngeal nerve (RLN) injury remains a challenge due to the lack of effective treatments. In this study, we established a new drug delivery system consisting of a tube of Heal-All Oral Cavity Repair Membrane loaded with laminin and neurotrophic factors and tested its ability to promote functional recovery following RLN injury. We created recombinant fusion proteins consisting of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) fused to laminin-binding domains (LBDs) in order to prevent neurotrophin diffusion. LBD-BDNF, LBD-GDNF, and laminin were injected into a collagen tube that was fitted to the ends of the transected RLN in rats. Functional recovery was assessed 4, 8, and 12 weeks after injury. Although vocal fold movement was not restored until 12 weeks after injury, animals treated with the collagen tube loaded with laminin, LBD-BDNF and LBD-GDNF showed improved recovery in vocalisation, arytenoid cartilage angles, compound muscle action potentials and regenerated fibre area compared to animals treated by autologous nerve grafting (p < 0.05). These results demonstrate the drug delivery system induced nerve regeneration following RLN transection that was superior to that induced by autologus nerve grafting. It may have potential applications in nerve regeneration of RLN transection injury.

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“…The PM scaffold has already been shown to be compatible with a variety of cells commonly used in the concept of supporting axonal regeneration, including OEC (Mollers et al, ). More detailed studies with PM combined with SC or predifferentiated mesenchymal stroma cells (dMSC) showed structural and functional axonal regeneration 12 weeks after implantation in a 20‐mm rat sciatic nerve defect (Boecker et al, ; Bozkurt et al, ).…”

Section: Introductionmentioning

confidence: 99%

Cell-enrichment with olfactory ensheathing cells has limited local extra beneficial effects on nerve regeneration supported by the nerve guide Perimaix

Bozkurt

Kim

Altinova

et al. 2018

J Tissue Eng Regen Med

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The reconstruction of peripheral nerve injuries is clinically challenging, and today, the autologous nerve transplantation is still considered as the only gold standard remedy for nerve lesions where a direct nerve coaptation is not possible. Nevertheless, the functional merits of many biomaterials have been tested as potential substitutes for the autologous nerve transplant. One of the strategies that have been pursued is the combination of bioengineered nerve guides with cellular enrichment. In this present study, we combined the previously evaluated collagen-based and microstructured nerve guide Perimaix with olfactory ensheathing cell enrichment. Rat sciatic nerve defects of 20 mm were either bridged by a cell-seeded or nonseeded nerve guide or an autologous nerve transplant. Animals were monitored for 12 weeks for structural and functional parameters. Seeded cells survived on Perimaix, and following implantation aligned along the microstructured Perimaix framework. Axonal densities within the cell-seeded nerve guides were higher than in the nonseeded nerve guides and were comparable to the autograft. Additionally, cell-seeding had local beneficial effects on myelination within the nerve guide, as myelin sheath thickness was enhanced when compared with the empty scaffold. Nevertheless, for bridging the nerve gap of 20 mm, both the cell-seeded as well as nonseeded scaffolds were equally efficient regarding the functional outcome, which did not differ between the autograft, seeded or nonseeded groups. Our data demonstrate that olfactory ensheathing cell enrichment has local effects on nerve regeneration in combination with the Perimaix nerve guide. Surprisingly, for traversing the lesion gap, additional cell-seeding is not crucial.

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Efficient bridging of 20 mm rat sciatic nerve lesions with a longitudinally micro-structured collagen scaffold

Cited by 69 publications

References 58 publications

Promoting peripheral myelin repair

Promoting peripheral myelin repair

Functional regeneration of the transected recurrent laryngeal nerve using a collagen scaffold loaded with laminin and laminin-binding BDNF and GDNF

Cell-enrichment with olfactory ensheathing cells has limited local extra beneficial effects on nerve regeneration supported by the nerve guide Perimaix

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