Laminin-coated poly(L-lactide) filaments induce robust neurite growth while providing directional orientation.
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.
Rangappa
N
N
Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9130, USA.
Romero
A
A
Nelson
K D
KD
Eberhart
R C
RC
Smith
G M
GM
D000818:Animals; D001672:Biocompatible Materials; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000502:physiology / Q000648:ultrastructure; D007797:Laminin; D008422:Materials Testing; D009416:Nerve Regeneration; D016501:Neurites / Q000502:physiology / Q000648:ultrastructure*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000502:physiology / Q000648:ultrastructure; D011091:Polyesters; D051381:Rats; D013499:Surface Properties
D001672:Biocompatible Materials; D007797:Laminin; D011091:Polyesters; C033616:poly(lactide)