Tissue Engineered Bands of Büngner for Accelerated Motor and Sensory Axonal Outgrowth.
Autor: | Panzer KV; Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States.; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States., Burrell JC; Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States.; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States., Helm KVT; Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States., Purvis EM; Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States.; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Zhang Q; Department of Oral and Maxillofacial Surgery, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Department of Oral and Maxillofacial Surgery, Penn Medicine Hospital of University of Pennsylvania, Philadelphia, PA, United States., Le AD; Department of Oral and Maxillofacial Surgery, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Department of Oral and Maxillofacial Surgery, Penn Medicine Hospital of University of Pennsylvania, Philadelphia, PA, United States., O'Donnell JC; Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States., Cullen DK; Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States.; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States. |
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Jazyk: | angličtina |
Zdroj: | Frontiers in bioengineering and biotechnology [Front Bioeng Biotechnol] 2020 Nov 20; Vol. 8, pp. 580654. Date of Electronic Publication: 2020 Nov 20 (Print Publication: 2020). |
DOI: | 10.3389/fbioe.2020.580654 |
Abstrakt: | Following peripheral nerve injury comprising a segmental defect, the extent of axon regeneration decreases precipitously with increasing gap length. Schwann cells play a key role in driving axon re-growth by forming aligned tubular guidance structures called bands of Büngner, which readily occurs in distal nerve segments as well as within autografts - currently the most reliable clinically-available bridging strategy. However, host Schwann cells generally fail to infiltrate large-gap acellular scaffolds, resulting in markedly inferior outcomes and motivating the development of next-generation bridging strategies capable of fully exploiting the inherent pro-regenerative capability of Schwann cells. We sought to create preformed, implantable Schwann cell-laden microtissue that emulates the anisotropic structure and function of naturally-occurring bands of Büngner. Accordingly, we developed a biofabrication scheme leveraging biomaterial-induced self-assembly of dissociated rat primary Schwann cells into dense, fiber-like three-dimensional bundles of Schwann cells and extracellular matrix within hydrogel micro-columns. This engineered microtissue was found to be biomimetic of morphological and phenotypic features of endogenous bands of Büngner, and also demonstrated 8 and 2× faster rates of axonal extension in vitro from primary rat spinal motor neurons and dorsal root ganglion sensory neurons, respectively, compared to 3D matrix-only controls or planar Schwann cells. To our knowledge, this is the first report of accelerated motor axon outgrowth using aligned Schwann cell constructs. For translational considerations, this microtissue was also fabricated using human gingiva-derived Schwann cells as an easily accessible autologous cell source. These results demonstrate the first tissue engineered bands of Büngner (TE-BoBs) comprised of dense three-dimensional bundles of longitudinally aligned Schwann cells that are readily scalable as implantable grafts to accelerate axon regeneration across long segmental nerve defects. (Copyright © 2020 Panzer, Burrell, Helm, Purvis, Zhang, Le, O’Donnell and Cullen.) |
Databáze: | MEDLINE |
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