Regulated Growth Factor Delivery for Nerve Regeneration
Background: Options for successful repair of peripheral nerves after traumatic injury remain suboptimal. Current strategies are limited to transfer of donor nerves from functional areas, with substantial donor-site morbidity and variable outcomes. The development of tissue-engineering strategies offers significant hope to patients facing functional impairment and cosmetic problems after such injuries. Tissue-engineered constructs used to bridge nerve gaps have the potential to improve options for the regeneration of peripheral nerves after transaction and the restoration of function. However these constructs must be rendered bioactive to be effective. One method of creating bioactive constructs involves the delivery of growth factors necessary for nerve repair and development. Technology: University of California, Irvine researchers have developed a method to deliver NGF (nerve growth factor) within previously fabricated biodegradable polymer conduits as an instigator of axonal/Schwann cell interaction to enhance peripheral nerve regeneration. Human embryonic kidney (EcR-293) have been stably and inducibly (by Ponasterone-A) transfected with an expression plasmid to secrete bioactive NGF in vitro and within poly- L-lactic acid (PLLA) conduits.
With the stable integration of a herpes simplex virus thymidine kinase (HSV-TK) suicide gene, these genetically modified hNGF-EcR-293 cells can be eliminated upon the administration of Ganciclovir. The application of Ganciclovir allows for the downregulation of NGF at a time point to be determined. This regulatory NGF system can enhance nerve regeneration across clinically sized transected peripheral sciatic nerves. Application: Clinical applications include an inducible delivery system to regulate and deliver NGF to tissue-engineered constructs making them bioactive. This NGF delivery system may decrease morbidity and improve outcomes for patient with peripheral nerve injuries. This method may also be used in further development of tissue engineered nerve constructs.
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