Development of a tissue engineered implantable device for the surgical repair of the peripheral nervous system

Georgiou, Melanie (2013). Development of a tissue engineered implantable device for the surgical repair of the peripheral nervous system. PhD thesis The Open University.



Peripheral nerve injury as a result of trauma affects approximately 1 million people in Europe and America annually. The current clinical gold standard treatment for repairing long gaps is the nerve autograft, in which only ~50% of cases result in satisfactory functional recovery. Tissue-engineered cellular bridging devices for surgical implantation into peripheral nerve injury sites could provide an attractive alternative to the autograft. This project reports the development of a robust, anisotropic biomaterial with highly aligned cells that can form the basis of a peripheral nerve repair device.

Engineered neural tissue (EngNT), which is formed from columns of Schwann cells or stem cells within a 3D aligned collagen matrix, can promote directed neurite outgrowth in vitro. This study demonstrates that sheets of EngNT can be arranged to form the 'endoneurium' of a peripheral nerve repair device within a NeuraWrap™ outer tube, and can be used for the repair of critical sized defects in rat.

Schwann cells are the preferred cell type for peripheral nerve repair because of their ability to enhance axon migration and secrete factors that further increase regeneration. However the use of autologous Schwann cells has a number of disadvantages, including the sacrifice of host nerve tissue for their extraction and slow expansion times in vitro. Various therapeutic cell types and a bovine collagen source that can potentially be used to make EngNT to form the device core were investigated. EngNT devices containing Schwann cell-like cells from adipose-derived stem cells (dADSC) or human neural progenitor cells differentiated to glial cells (dCX) were tested in a critical sized gap in the rat sciatic nerve model. The in vivo experiments demonstrated that there is potential, for the dADSCs to be used for peripheral nerve repair. The results from the dCX repairs were less clear.

The technology reported here offers a simple, rapid and effective method for the manufacture of an aligned cellular biomaterial, and could be applied to a range of tissue engineering applications. This study demonstrates that there is potential for EngNT to be used in the construction of nerve repair conduits.

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