Multichannel silk protein/laminin grafts for spinal cord injury repair

Abstract

The physical, chemical, and bioactive cues provided by biomaterials are critical for spinal cord regeneration following injury. In this study, we investigated the bioactivity of a silk-based scaffold for nerve tissue remodeling that featured morphological guidance in the form of ridges as well as bioactive molecules. Multichannel/laminin (LN) silk scaffolds stimulated growth, development, and the extension of primary hippocampal neurons after 7 days of culture in vitro. And then, the multichannel/LN silk scaffolds were implanted into 2-mm-long hemisection defects in Sprague-Dawley rat spinal cords for 70 days to evaluate their bioactivities of spinal cord remolding. Our results demonstrated that animal behavior was significantly improved in the multichannel/LN group, as evaluated by Basso-Beattie-Bresnahan score, whereas the implantation of multichannels and random pores groups resulted in recurring limps. Moreover, histology and immunohistochemical staining revealed an increase in blood vessels and expression of growth associated protein-43 and neurofilament-200 as well as reduced expression of glial fibrillary acidic protein in the multichannel/LN group, which contributed to the rebuilding of spinal cord defects. Thus, multichannel/LN silk scaffolds mediated cell migration, stimulated blood capillary formation, and promoted axonal extension, suggesting the utility of these scaffolds for spinal cord reconstruction. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3045-3057, 2016.

A Review of Structure Construction of Silk Fibroin Biomaterials from Single Structures to Multi-Level Structures

“…The multichannel SF scaffolds were implanted in Sprague-Dawley rat spinal cords for bioactivity evaluation. It was found that the SF scaffolds could mediate cell migration, promote blood capillary formation, and help axonal extension, which suggested the application of the multichannel SF scaffolds for spinal cord injury regeneration [93]. Han et al prepared water-insoluble SF scaffolds containing physical cues instead of growth factors for vascularization.…”

Roles of Mesenchymal Stem Cells in Spinal Cord Injury

“…In addition, the layered architecture of the scaffold appeared to induce cell/tissue polarity and promote longitudinal growth of neurites within the graft [103]. Also, multichannel/laminin (LN) silk scaffolds could mediate cell migration, stimulate blood capillary formation, and promote axonal extension, suggesting a strong correlation between scaffold topography and growth behavior of stem cells [104]. More intensive studies are required for the investigation of the activities of stem cells after being combined with biomaterials to offer insights into the design and development of nerve tissue engineering scaffold especially for SCI (Figure 1) [105].…”

Pathologic Remodeling of Endoneurial Tubules in Human Neuromas

“…Laminins play an important role in axonal guidance. Laminin has been used as a substrate for nerve conduits to guide axonal growth in a variety of settings [ 10 - 11 ] and has been used during tissue engineering approaches [ 12 - 13 ]. Laminin specifically induces signaling pathways, including PI-3-kinase [ 14 ].…”