Bioactive Silk‐Based Nerve Guidance Conduits for Augmenting Peripheral Nerve Repair

Magaz, Adrián; Faroni, Alessandro; Gough, Julie E.; Reid, Adam J.; Xu, Li; Blaker, Jonny J.

doi:10.1002/adhm.201800308

Cited by 105 publications

(79 citation statements)

References 294 publications

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“…The second incision site bears the additional risk of donor site morbidity, neuroma formation, and pain [7,10]. To overcome these disadvantages, current research focusses on the improvement of artificial nerve conduits or decellularized nerve allografts enriched with cells or biological components such as growth factors, peptides, or ECM molecules [11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization

Haertinger

Weiss

Mann

et al. 2020

Cells

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Recent studies showed a beneficial effect of adipose stem cell-derived extracellular vesicles (ADSC-EVs) on sciatic nerve repair, presumably through Schwann cell (SC) modulation. However, it has not yet been elucidated whether ADSC-EVs exert this supportive effect on SCs by extracellular receptor binding, fusion to the SC membrane, or endocytosis mediated internalization. ADSCs, ADSC-EVs, and SCs were isolated from rats and characterized according to associated marker expression and properties. The proliferation rate of SCs in response to ADSC-EVs was determined using a multicolor immunofluorescence staining panel followed by automated image analysis. SCs treated with ADSC-EVs and silica beads were further investigated by 3-D high resolution confocal microscopy and live cell imaging. Our findings demonstrated that ADSC-EVs significantly enhanced the proliferation of SCs in a time- and dose-dependent manner. 3-D image analysis revealed a perinuclear location of ADSC-EVs and their accumulation in vesicular-like structures within the SC cytoplasm. Upon comparing intracellular localization patterns of silica beads and ADSC-EVs in SCs, we found striking resemblance in size and distribution. Live cell imaging visualized that the uptake of ADSC-EVs preferentially took place at the SC processes from which the EVs were transported towards the nucleus. This study provided first evidence for an endocytosis mediated internalization of ADSC-EVs by SCs and underlines the therapeutic potential of ADSC-EVs in future approaches for nerve regeneration.

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Section: Introductionmentioning

confidence: 99%

Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization

Haertinger

Weiss

Mann

et al. 2020

Cells

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“…Axon regeneration is extensive through conduits composed of fibrin [145,153], hydrogel tubes [154], alginate/chitosan polyelectrolyte [155][156][157], poly epsilon-caprolactone [158,159], polyglycolic acid [160], poly(lactic-co-glycolic acid) or silk-based [161][162][163][164]. Conduits composed of decellularized human umbilical artery [165] and muscles [166] are also effective in promoting axon regeneration across nerve gaps.…”

Section: Conduit Compositionmentioning

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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“…Following an injury in the peripheral nervous system, the denervated Schwann cells not only provide a trophic support but also dedifferentiate, proliferate, and migrate to the wounded area to form the bands of Büngner, encouraging axon regrowth and nerve regeneration. [54,55] To simulate this scenario, we also fabricated a bidirectional density gradient of biomacromolecular particles on a scaffold made of uniaxially aligned nanofibers, with the density increasing from the two opposite sides to the center. As such, we were able to mimic the migration of Schwann cells from both the proximal and distal ends of the served nerve toward the center of the injured site.…”

Section: Bidirectional Migration Of Schwann Cellsmentioning

confidence: 99%

Promoting Cell Migration and Neurite Extension along Uniaxially Aligned Nanofibers with Biomacromolecular Particles in a Density Gradient

Xue

Qiu

et al. 2020

Adv Funct Materials

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A simple method based upon masked electrospray is reported for directly generating both unidirectional and bidirectional density gradients of biomacromolecular particles on uniaxially aligned nanofibers. The method has been successfully applied to different types of biomacromolecules, including collagen and a mixture of collagen and fibronectin or laminin, to suit different types of applications. Collagen particles in a unidirectional or bidirectional gradient are able to promote the linear migration of bone marrow stem cells or NIH-3T3 fibroblasts along the direction of increasing particle density. In the case of particles made of a mixture of collagen and fibronectin, their deposition in a bidirectional gradient promotes the migration of Schwann cells from two opposite sides toward the center, matching the scenario in peripheral nerve repair. As for a mixture of collagen and laminin, the particles in a unidirectional gradient promote the extension of neurites from embryonic chick dorsal root ganglion in the direction of increasing particle density. Taken together, the scaffolds featuring a combination of uniaxially aligned nanofibers and biomacromolecular particles in density gradient can be applied to a range of biological studies and biomedical applications.

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Bioactive Silk‐Based Nerve Guidance Conduits for Augmenting Peripheral Nerve Repair

Cited by 105 publications

References 294 publications

Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization

Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization

Restoration of Neurological Function Following Peripheral Nerve Trauma

Promoting Cell Migration and Neurite Extension along Uniaxially Aligned Nanofibers with Biomacromolecular Particles in a Density Gradient

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