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Following spinal cord injuries, the continuity of both the descending motor fiber tracts and ascending sensory fiber tract is disrupted by glial scar formation, which is considered the major impediment to axonal regeneration. While the inhibitory role of various molecular ligands of the glial scar have been extensively investigated and therapeutic interventions targeting these repulsive ligands have been shown to facilitate axonal regeneration, very few studies have looked at the physical role that the glial scar plays in inhibiting regeneration due to its highly disorganized structure. Our lab is interested in understanding whether axonal regeneration could be facilitated by restoring the organized framework of nerve fiber tracts. We have developed an in vitro model to align astrocyte monolayers on culture substrates using nano-chemically patterned anisotropic adhesive ligand patterns. The aligned astrocyte monolayers guided regenerating neurite outgrowth and enhanced their directed outgrowth length. Using the same methodology, recently we engineered 3-D oriented astrocyte constructs that are mechanically stable and implantable. The oriented constructs preserve the same cellular anisotropy as their 2-D counterparts throughout the thickness. Currently, this ongoing project is focusing on investigating the therapeutic potential of these 3-D oriented astrocyte constructs in spinal cord injury repair.
Recent Posters:
A 3D Scaffold-Free Aligned Astrocyte Construct for Therapeutic Applications
Recent Publications:
Smeal RM, Tresco PA, The influence of substrate curvature on neurite outgrowth is cell type dependent. Exp Neurol. 2008 Oct;213(2):281-92. Epub 2008 Jun 16. [Link]
Wen X, Tresco P, Effect of filament diameter and extracellular matrix molecule precoating on neurite outgrowth and Schwann cell behavior on multifilament entubulation bridging device in vitro. J Biomed Mater Res A 2006 Mar 1;76(3):626-37. [Link]
Wen X, Tresco P, Effect of filament diameter and extracellular matrix molecule precoating on neurite outgrowth and Schwann cell behavior on multifilament entubulation bridging device in vitro. J Biomed Mater Res A 2006 Mar 1;76(3):626-37. [Link]
Walsh JF, Manwaring ME, Tresco P, Directional neurite outgrowth is enhanced by engineered meningeal cell-coated substrates. Tissue Eng 2005 Jul-Aug;11(7-8):1085-94. [Link] |
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Neuronal Guidance |
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The Keck Center for Tissue Engineering |
