NSC-derived extracellular matrix-modified GelMA hydrogel fibrous scaffolds for spinal cord injury repair

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Abstract

Cell-derived extracellular matrix (ECM) has been applied in spinal cord injury (SCI) regeneration because of its various biological functions. However, insufficient mechanical properties limit its wide application. Herein, we developed GelMA/ECM hydrogel fibrous scaffolds (GelMA/ECM scaffolds) that can recruit and enhance the differentiation of neural stem cells (NSCs) by electrospinning and decellularization techniques. Moreover, the GelMA/ECM scaffolds had good mechanical properties and reinforced cell adhesion and proliferation. Compared to GelMA hydrogel fibrous scaffolds (GelMA scaffolds), GelMA/ECM scaffolds promoted more NSCs toward neurons by markedly enhancing the expression of MAP-2 and Tuj-1 and decreasing GFAP expression. In addition, the GelMA/ECM scaffolds significantly reduced the proportion of M1-phenotype macrophages, which is favorable for SCI repair. In vivo, the GelMA/ECM scaffolds recruited NSCs at the injured site, promoted neuron regeneration, and reduced the formation of glial scars and the inflammatory response, which further led to a significant improvement in the functional recovery of SCI. Therefore, this scaffold shows potential in regenerative medicine, mainly in SCI.

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Functional structure and composition of the extracellular matrix.

Fred T Bosman, Ivan Stamenkovic (2003)

In this brief introductory paper the general structure and the molecular composition of the extracellular matrix are outlined. Ultrastructural morphology of the extracellular matrix is introduced and subsequently the molecular structure of each of the main protein families, which together make up the extracellular matrix, is reviewed. Collagens, laminins, tenascins, and proteoglycans are addressed. An important common feature is the domain structure of these in general very large proteins. Several families have domains in common, which favours extensive interactions. Integrins play an important role in these interactions and also in the communication between cells and the matrix. The extracellular matrix appears to be a very dynamic structure, which has a prominent role in normal development as well as in a variety of disease processes. Matrix metalloproteinases are essential actors in this complex interplay between cells and the extracellular matrix. Copyright 2003 John Wiley & Sons, Ltd.

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Directing Induced Pluripotent Stem Cell Derived Neural Stem Cell Fate with a Three-Dimensional Biomimetic Hydrogel for Spinal Cord Injury Repair

Lei Fan, Can Liu, Zhengnan Zhou … (2018)

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Chitosan/silk fibroin-based, Schwann cell-derived extracellular matrix-modified scaffolds for bridging rat sciatic nerve gaps.

Yun Gu, Jianbin Zhu, Chengbin Xue … (2014)

Extracellular matrix (ECM) plays a prominent role in establishing and maintaining an ideal microenvironment for tissue regeneration, and ECM scaffolds are used as a feasible alternative to cellular and molecular therapy in the fields of tissue engineering. Because of their advantages over tissue-derived ECM scaffolds, cultured cell-derived ECM scaffolds are beginning to attract attention, but they have been scarcely studied for peripheral nerve repair. Here we aimed to develop a tissue engineered nerve scaffold by reconstituting nerve cell-derived ECM with natural biomaterials. A protocol was adopted to prepare and characterize the cultured Schwann cell (SC)-derived ECM. A chitosan conduit and silk fibroin (SF) fibers were prepared, cultured with SCs for ECM deposition, and subjected to decellularization, followed by assembly into a chitosan/SF-based, SC-derived ECM-modified scaffold, which was used to bridge a 10 mm rat sciatic nerve gap. The results from morphological analysis as well as electrophysiological examination indicated that regenerative outcomes achieved by our developed scaffold were similar to those by an acellular nerve graft (namely a nerve tissue-derived ECM scaffold), but superior to those by a plain chitosan/SF scaffold. Moreover, blood and histopathological parameters confirmed the safety of scaffold modification by SC-derived ECM. Therefore, a hybrid scaffold based on joint use of acellular and classical biomaterials represents a promising approach to nerve tissue engineering.