scholarly journals The Physicochemical Properties of Decellularized Extracellular Matrix-Coated 3D Printed Poly(ε-caprolactone) Nerve Conduits for Promoting Schwann Cells Proliferation and Differentiation

Materials ◽  
2018 ◽  
Vol 11 (9) ◽  
pp. 1665 ◽  
Author(s):  
Chung-Chia Chen ◽  
Joyce Yu ◽  
Hooi-Yee Ng ◽  
Alvin Lee ◽  
Chien-Chang Chen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Alternative Methods ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specific Class ◽  
Nerve Grafting ◽  
Decellularized Extracellular Matrix ◽  
Nerve Conduits ◽  
3D Printed

Although autologous nerve grafting remains the gold standard treatment for peripheral nerve injuries, alternative methods such as development of nerve guidance conduits have since emerged and evolved to counter the many disadvantages of nerve grafting. However, the efficacy and viability of current nerve conduits remain unclear in clinical trials. Here, we focused on a novel decellularized extracellular matrix (dECM) and polydopamine (PDA)-coated 3D-printed poly(ε-caprolactone) (PCL)-based conduits, whereby the PDA surface modification acts as an attachment platform for further dECM attachment. We demonstrated that dECM/PDA-coated PCL conduits possessed higher mechanical properties when compared to human or animal nerves. Such modifications were proved to affect cell behaviors. Cellular behaviors and neuronal differentiation of Schwann cells were assessed to determine for the efficacies of the conduits. There were some cell-specific neuronal markers, such as Nestin, neuron-specific class III beta-tubulin (TUJ-1), and microtubule-associated protein 2 (MAP2) analyzed by enzyme-linked immunosorbent assay, and Nestin expressions were found to be 0.65-fold up-regulated, while TUJ1 expressions were 2.3-fold up-regulated and MAP2 expressions were 2.5-fold up-regulated when compared to Ctl. The methodology of PDA coating employed in this study can be used as a simple model to immobilize dECM onto PCL conduits, and the results showed that dECM/PDA-coated PCL conduits can as a practical and clinically viable tool for promoting regenerative outcomes in larger peripheral nerve defects.

scholarly journals Fibroblasts Colonizing Nerve Conduits Express High Levels of Soluble Neuregulin1, a Factor Promoting Schwann Cell Dedifferentiation

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1366 ◽  
Author(s):  
Benedetta E. Fornasari ◽  
Marwa El Soury ◽  
Giulia Nato ◽  
Alessia Fucini ◽  
Giacomo Carta ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
Good Alternative ◽  
Cell Dedifferentiation ◽  
Nerve Conduits ◽  
Early Regeneration

Conduits for the repair of peripheral nerve gaps are a good alternative to autografts as they provide a protected environment and a physical guide for axonal re-growth. Conduits require colonization by cells involved in nerve regeneration (Schwann cells, fibroblasts, endothelial cells, macrophages) while in the autograft many cells are resident and just need to be activated. Since it is known that soluble Neuregulin1 (sNRG1) is released after injury and plays an important role activating Schwann cell dedifferentiation, its expression level was investigated in early regeneration steps (7, 14, 28 days) inside a 10 mm chitosan conduit used to repair median nerve gaps in Wistar rats. In vivo data show that sNRG1, mainly the isoform α, is highly expressed in the conduit, together with a fibroblast marker, while Schwann cell markers, including NRG1 receptors, were not. Primary culture analysis shows that nerve fibroblasts, unlike Schwann cells, express high NRG1α levels, while both express NRG1β. These data suggest that sNRG1 might be mainly expressed by fibroblasts colonizing nerve conduit before Schwann cells. Immunohistochemistry analysis confirmed NRG1 and fibroblast marker co-localization. These results suggest that fibroblasts, releasing sNRG1, might promote Schwann cell dedifferentiation to a “repair” phenotype, contributing to peripheral nerve regeneration.

scholarly journals Peripheral Nerve Repair with Cultured Schwann Cells: Getting Closer to the Clinics

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Maria Carolina O. Rodrigues ◽  
Antonio Antunes Rodrigues ◽  
Loren E. Glover ◽  
Julio Voltarelli ◽  
Cesario V. Borlongan
Keyword(s):  
Bone Marrow ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Repair ◽  
Experimental Studies ◽  
Experimental Treatment ◽  
Mesenchymal Cells ◽  
Nerve Conduits ◽  
Cultured Schwann Cells

Peripheral nerve injuries are a frequent and disabling condition, which affects 13 to 23 per 100.000 persons each year. Severe cases, with structural disruption of the nerve, are associated with poor functional recovery. The experimental treatment using nerve grafts to replace damaged or shortened axons is limited by technical difficulties, invasiveness, and mediocre results. Other therapeutic choices include the adjunctive application of cultured Schwann cells and nerve conduits to guide axonal growth. The bone marrow is a rich source of mesenchymal cells, which can be differentiatedin vitrointo Schwann cells and subsequently engrafted into the damaged nerve. Alternatively, undifferentiated bone marrow mesenchymal cells can be associated with nerve conduits and afterward transplanted. Experimental studies provide evidence of functional, histological, and electromyographical improvement following transplantation of bone-marrow-derived cells in animal models of peripheral nerve injury. This paper focuses on this new therapeutic approach highlighting its direct translational and clinical utility in promoting regeneration of not only acute but perhaps also chronic cases of peripheral nerve damage.

3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair

Biomaterials ◽  
2017 ◽  
Vol 112 ◽  
pp. 264-274 ◽  
Author(s):  
Jinah Jang ◽  
Hun-Jun Park ◽  
Seok-Won Kim ◽  
Heejin Kim ◽  
Ju Young Park ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Cardiac Repair ◽  
Decellularized Extracellular Matrix ◽  
3D Printed ◽  
Tissue Construct

Beta 4 integrin expression in myelinating Schwann cells is polarized, developmentally regulated and axonally dependent

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1287-1301 ◽  
Author(s):  
M.L. Feltri ◽  
S.S. Scherer ◽  
R. Nemni ◽  
J. Kamholz ◽  
H. Vogelbacker ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Morphological Changes ◽  
Cell Phenotype ◽  
Integrin Subunit ◽  
Integrin Expression ◽  
Cultured Schwann Cells ◽  
Mediate Cell

In developing and regenerating peripheral nerve, Schwann cells interact with axons and extracellular matrix in order to ensheath and myelinate axons. Both of these interactions are likely to be mediated by adhesion molecules, including integrins, which mediate cell-cell and cell-extracellular matrix interactions. Recently, the beta 4 integrin subunit was reported to be expressed by Schwann cells in peripheral nerve. We have examined the expression of beta 4, beta 1 and their common heterodimeric partner, the alpha 6 integrin subunit, in developing and regenerating rat peripheral nerve. beta 4 and alpha 6 are enriched in peripheral nerve and they co-localize at the abaxonal surface of myelinating Schwann cells, opposite the Schwann cell basal lamina, which contains possible ligands of alpha 6 beta 4. In contrast, beta 4 and alpha 6 are expressed in a different pattern in non-myelinating Schwann cells. The level of beta 4, but not alpha 6 or beta 1 mRNAs, increases progressively in developing nerves, reaching a peak in adult nerves well after the peak of the myelin-specific mRNAs. After axotomy, the expression of beta 4 mRNA and protein, but not alpha 6 or beta 1 mRNAs, fall rapidly but subsequently are reinduced by regenerating axons. Similarly, in cultured Schwann cells, the expression of beta 4 mRNA, but not alpha 6 mRNA, is significantly modulated by forskolin, a drug that elevates cAMP and mimics some of the effects of axonal contact. beta 4 integrin expression in Schwann cells, therefore, is regulated by Schwann cell-axon interactions, which are known to be critical in determining the Schwann cell phenotype. Furthermore, the polarized expression of alpha 6 beta 4 to the abaxonal surface of myelinating Schwann cells suggests that alpha 6 beta 4 may mediate in part the morphological changes required of Schwann cells in the process of myelination in the peripheral nervous system.

scholarly journals Artificial decellularized extracellular matrix improves the regenerative capacity of adipose tissue derived stem cells on 3D printed polycaprolactone scaffolds

2021 ◽  
Vol 12 ◽  
pp. 204173142110222
Author(s):  
Jana C Blum ◽  
Thilo L Schenck ◽  
Alexandra Birt ◽  
Riccardo E Giunta ◽  
Paul S Wiggenhauser
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Extracellular Matrix ◽  
Cartilage Regeneration ◽  
Regenerative Capacity ◽  
Decellularized Extracellular Matrix ◽  
In Vitro Investigation ◽  
3D Printed ◽  
Artificial Extracellular Matrix

Ideal tissue engineering frameworks should be both an optimal biological microenvironment and a shape and stability providing framework. In this study we tried to combine the advantages of cell-derived artificial extracellular matrix (ECM) with those of 3D printed polycaprolactone (PCL) scaffolds. In Part A, both chondrogenic and osteogenic ECMs were produced by human adipose derived stem cells (hASCs) on 3D-printed PCL scaffolds and then decellularized to create cell free functionalized PCL scaffolds, named acPCL and aoPCL respectively. The decellularization resulted in a significant reduction of the DNA content as well as the removal of nuclei while the ECM was largely preserved. In Part B the bioactivation and the effect of the ac/aoPCL scaffolds on the proliferation, differentiation, and gene expression of hASCs was investigated. The ac/aoPCL scaffolds were found to be non-toxic and allow good adhesion, but do not affect proliferation. In the in vitro investigation of cartilage regeneration, biochemical analysis showed that acPCL scaffolds have an additional effect on chondrogenic differentiation as gene expression analysis showed markers of cartilage hypertrophy. The aoPCL showed a large influence on the differentiation of hASCs. In control medium they were able to stimulate hASCs to produce calcium alone and all genes relevant investigated for osteogenesis were significantly higher expressed on aoPCL than on unmodified PCL. Therefore, we believe that ac/aoPCL scaffolds have a high potential to improve regenerative capacity of unmodified PCL scaffolds and should be further investigated.

Autologous Tendons Used as Grafts for Bridging Peripheral Nerve Defects

1999 ◽  
Vol 24 (3) ◽  
pp. 284-290 ◽  
Author(s):  
J. BRANDT ◽  
L. B. DAHLIN ◽  
G. LUNDBORG
Keyword(s):  
Extracellular Matrix ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Repair ◽  
The Third ◽  
Extracellular Matrix Components ◽  
Matrix Components ◽  
Tail Tendon ◽  
Rat Tail

This study was performed to investigate whether autologous collagen and other extracellular matrix components could be used in nerve repair by bridging a 10 mm defect in the rat sciatic nerve. Three models of repair were examined. In the first model, a rat tail tendon was teased and subsequently rolled to form a loose collagen roll which was sutured over the defect. In the second model, an intact tendon was used. In the third model, a teased tendon was pretreated with attachment of nerve segments to each end for 4 weeks before grafting. Both teased and intact tendons supported regeneration, to some extent. Pretreatment resulted in migration of Schwann cells into the graft, and enhanced regeneration.

scholarly journals Past, Present, and Future of Nerve Conduits in the Treatment of Peripheral Nerve Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Aikeremujiang Muheremu ◽  
Qiang Ao
Keyword(s):  
Stem Cells ◽  
Clinical Practice ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Neurotrophic Factors ◽  
Peripheral Nerve Injury ◽  
Functional Outcomes ◽  
Nerve Conduits ◽  
New Construction

With significant advances in the research and application of nerve conduits, they have been used to repair peripheral nerve injury for several decades. Nerve conduits range from biological tubes to synthetic tubes, and from nondegradable tubes to biodegradable tubes. Researchers have explored hollow tubes, tubes filled with scaffolds containing neurotrophic factors, and those seeded with Schwann cells or stem cells. The therapeutic effect of nerve conduits is improving with increasing choice of conduit material, new construction of conduits, and the inclusion of neurotrophic factors and support cells in the conduits. Improvements in functional outcomes are expected when these are optimized for use in clinical practice.

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