Micro and nanopatterned biodegradable polymer films for peripheral nerve regeneration

Miller, Cheryl
Major Professor
Surya K. Mallapragada
Committee Member
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Theses & dissertations (Interdisciplinary)

Annually over 200,000 surgeries are attempted to repair peripheral nerve damage.1 Without these surgeries, peripheral nerve transections have little hope of reinnervating the effector organ and becoming fully functional if the nerve endings are separated by a centimeter or more. Currently, transections are repaired with nerve autografts removed from one part of the body to repair the injured site. Autografting causes deinnervation of the donor site and tissue availability is limited.;An alternative nerve repair method to grafting is an entubulization method where a conduit is used to connect the nerve endings. The conduit allows for chemical communications between the nerve stumps and also provides physical guidance for the regenerating neurites.;By using a conduit to engineer an artificial environment that mimics the physical and chemical stimulus that promotes peripheral nerve regeneration, faster and more direct regeneration may be possible.;The purpose of this project was to investigate cellular activities that direct and guide peripheral nerve outgrowth in vitro. Micro and nanopatterned biodegradable polymer films of poly(DL-lactide) and poly(lactide-co-g1ycolide) were fabricated to provide physical guidance. The patterned surface was chemically modified with laminin to contribute neurotrophic factors and then seeded Schwann cells, which furnish biological cues.;The results show that Schwann cells and dissociated dorsal root ganglia (DRG) seeded separately on laminin coated micropatterned films of 10 mum groove width by 10 mum or 20 mum groove spacing align well due to the effects of the physical and chemical guidance mechanisms. The Schwann cells experienced 100% alignment on substrates with groove depths ranging from 1.5 to 3.3 mum and dissociated DRG aligned 77 +/- 3% on 3 mum deep patterns and 92 +/- 3% on groove depths of 4 mum. The laminin adsorption caused 8 times more Schwann cells and 5 times more dissociated DRG adhere to the films and the neurites had the added benefit of 3 times more outgrowth.;When simultaneously combining the physical effects of the grooves, the chemical influence of the laminin and biological enhancements from the Schwann cells, the synergistic effects caused the DRG to grow along the direction of the grooves at an accelerated rate.;1Medical Devices and Diagnostic Industry, pg. 3, August 1985.