Laminin-coated poly(L-lactide) filaments induce robust neurite growth while providing directional orientation

Abstract

Cellular channels during development and after peripheral nerve injury are thought to provide guidance cues to growing axons. In tissue culture where these cues are absent, neurites from dorsal root ganglion neurons grow with a radial distribution. To induce directional axonal growth and to enhance the rate of axonal growth after injury, we have designed microfilaments of poly(L-lactide). We demonstrate that dorsal root ganglia grown on these filaments in vitro extend longitudinally oriented neurites in a manner similar to native peripheral nerves. The extent of neurite growth was significantly higher on laminin-coated filaments compared with uncoated and poly-L-lysine-coated filaments. As high as 5.8 +/- 0.2 mm growth was observed on laminin-coated filaments compared with 2.0 +/- 0.2 mm on uncoated and 2.2 +/- 0.3 mm on poly-L-lysine-coated filaments within 8 days. Schwann cells were found to grow on all types of filaments. They were, however, absent in the leading edges of growth on laminin-coated filaments. Photolysis of Schwann cells caused a significant reduction in the neurite length on all types of filaments. Laminin-coated filaments, however, induced significantly longer neurites compared with uncoated and/or poly-L-lysine-coated filaments even in the absence of Schwann cells. Our results suggest that laminin-coated poly(L-lactide) filaments are suitable for inducing directional and enhanced axonal growth. Implants designed by arranging these microfilaments into bundles should aid regenerating axons by providing guidance cues and channels to organize matrix deposition, cell migration, axon growth, and improve functional recovery.

The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps

“…Topographical cues involving grooves and fibers have been previously demonstrated to cause Schwann cell alignment and subsequent neurite extension in vitro [13][14][15], and some studies have used magnetically aligned collagen filaments [16], microbraided polymer fibers [3], or micron-scale filaments to promote nerve regeneration [17,18]. In this study, the quantitative comparison of both DRG outgrowth in vitro and nerve regeneration in vivo on two different polymer surface topographies (i.e., aligned and randomly oriented fiber films, but with identical material and fabrication process) clearly provides key insights into the importance of the structural cues (i.e., alignment) for promoting nerve regeneration.…”

A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

“…Numerous studies have shown its ability to enhance Schwann proliferation and migration, as well as its direct effects on neurite outgrowth [13,36,70]. Laminin has been used most frequently for surface modification for NGC and for their respective structural components [13,36,46,55,68,70,74,75]. Other ECM molecules, such as collagen and fibronectin, have the ability to significantly increase SC adhesion as well as proliferation, and enhance neurite outgrowth however, although results have been shown to be significantly lower than that of laminin [13,73,74].…”

Photofabricated Gelatin-Based Nerve Conduits: Nerve Tissue Regeneration Potentials

“…Our previous study 35, [37][38][39]. The bioactive substances used are laminin and fibronectin, which are cell adhesion proteins and showed that the release of bioactive substances from photogels depends on the degree of swelling of the phowhich accelerate cell migration and proliferation (7,11,17,20,22,30,31,37,38). NGF is also used as a potent neutocured gel in water (21).…”

“…(7,11,17,20,37,38) and fibronectin (7,11,37) in a tubular Tokyo, Japan; maximum wavelength of illumination, 420-430 nm; and light intensity, 1.5 × 10 6 lx) for 15 min conduit. The other is to incorporate multiple contact guide artificial neurofilaments (20,22,(29)(30)(31)38,39) or using a custom-designed equipment. The photocured gelatin nerve conduit had the following dimensions: inmultimicroporous foams into a nerve conduit (10,18,27,36).…”