Krathika Bhat (Geesthacht, DE), Lisa Hanke (Kiel, DE), Dr. Heike Helmholz (Geesthacht, DE), Professor Eckhard Quandt (Kiel, DE), Dr. Sarah Pixley (Cincinnati, OH, US), Prof. Dr. Regine Willumeit-Römer (Geesthacht, DE; Kiel, DE)
Abstract text (incl. figure legends and references)
Peripheral nerve injury leading to long nerve gaps can result in incomplete recovery and require support to enable complete nerve regeneration. Wires made of biodegradable metals, like Magnesium (Mg), can potentially be used to bridge this nerve gap. In the nerve, Schwann cells play an important role in initiating and promoting successful nerve regeneration after injury. Hence, we tested the effect of Mg and Mg-1.8Li metal foils on Schwann cell functions such as MCP-1 secretion (macrophage recruitment), gene expression of neurotrophins and myelin. In order to study the effects in a nerve injury-like microenvironment, we developed an in vitro injury model. We tested two models for RT4 Schwannoma cells - freeze-killed Schwannoma cells and rat sciatic nerves. MCP-1 release was used as an injury marker, since injured Schwann cells release this chemokine to recruit macrophages and clear the injured debris. There was a dose-dependent increase in MCP-1 release due to both injury stimulants. However, the freeze-killed nerve extracts induced a quicker release of MCP-1, indicating that there are factors in addition to the cellular damage-associated molecules that contribute to the response. Using the freeze-killed cell extracts, we studied the influence of Mg and Mg-1.8Li foils in indirect contact with injury-stimulated Schwannoma cells. Both materials reduced MCP-1 release after 48 h of exposure. The presence of the metals along with the injury stimulant significantly downregulated Gdnf expression that was upregulated by injury. Furthermore, they siginificantly upregulated p75 expression which plays a positive role in the remyelination process. Both materials upregulated the expression of Mpz, the most abundant myelin protein. In conclusion, Mg-based materials when used as a support in nerve regeneration could reduce the pro-inflammatory response. The results also suggest that Mg could positively influence the remyelination and further in vivo studies could be useful.