Cooperative effect of heparan sulfate and laminin mimetic peptide nanofibers on the promotion of neurite outgrowth

Extracellular matrix contains an abundant variety of signals that are received by cell surface receptors contributing to cell fate, via regulation of cellular activities such as proliferation, migration and differentiation. Cues from extracellular matrix can be used for the development of materials to direct cells into their desired fate. Neural extracellular matrix (ECM) is rich in axonal growth inducer proteins, and by mimicking these permissive elements in the cellular environment, neural differentiation as well as neurite outgrowth can be induced. In this paper, we used a synthetic peptide nanofiber system that can mimic not only the activity of laminin, an axonal growth-promoting constituent of the neural ECM, but also the activity of heparan sulfate proteoglycans in order to induce neuritogenesis. Heparan sulfate mimetic groups that were utilized in our system have an affinity to growth factors and induce the neuroregenerative effect of laminin mimetic peptide nanofibers. The self-assembled peptide nanofibers with heparan sulfate mimetic and laminin-derived epitopes significantly promoted neurite outgrowth by PC-12 cells. In addition, these scaffolds were even effective in the presence of chondroitin sulfate proteoglycans (CSPGs), which are the major inhibitory components of the central nervous system. In the presence of these nanofibers, cells could overcome CSPG inhibitory effect and extend neurites on peptide nanofiber scaffolds.

Laminin-derived and heparan sulfate-mimetic molecules important for native neuronal extracellular matrix exhibit a cooperative effect in vitro. When used in combination, these bioactive molecules induce neurite outgrowth and overcome inhibitory effect of chondroitin sulfate proteoglycans, which are major inhibitory constituents of neuronal scar tissues that blocks neuroregeneration. This composite nanofiber system provides a promising novel therapeutic approach for neural regeneration after neuronal injury, due to its ability to act as an inductive element for neuroregeneration while blocking the activity of inhibitory elements.Figure optionsDownload high-quality image (200 K)Download as PowerPoint slide