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Dr. Pixley’s lab coordinates with an interdisciplinary group that spans UC Colleges, US universities, international partners and industrial partners. For over 10 years, this work has been part of an NSF Engineering Research Center (ERC) funding mechanism. This ERC was entitled Revolutionizing Metallic Biomaterials. Three US universities, several industrial partners and an international partner were involved. The Pixley lab focus has been on novel applications of metallic biomaterials, particularly to repair damaged nervous tissues. The particular application pursued to data has been peripheral nerve regeneration. While the ERC funding has now ended, the lab continues its partnership with engineers to advance biomedical repairs. Our most recent partnership is with an engineering team in Israel.
When substantial injuries occur that result in complete loss of peripheral nerve segments, surgical intervention is required. A scaffold is used to replace the lost segments and reconnect the two cut nerve endings. We seek to develop “man-made” or biomaterial scaffolds to avoid the hazards and dangers of using autografts (nerves from the same patient). In particular, we are interested in using a unique material, biodegradable metals (magnesium (Mg) and zinc (Zn)) as part of scaffolds. These metals have promise to provide a physical pathway to safely guide and support regenerating cells as they cross an injury gap in a nerve and regenerate a nerve segment.
Our research has shown that Mg and now Zn metal, in microfilament forms, have great promise to provide this type of contact guidance. Our goals now are to continue to refine the use of these biomaterials, as well as to develop a better understanding of the mechanisms by which nerve regeneration adapts to these unusual biomaterials, as a means to understand nerve regeneration and nerve repair in general.
The use of Mg, and more recently Zn as a material for biomedical implants has expanded rapidly over the last 10-15 years. Refinements in the purity of these metals has spurred these advances. The advantages of biodegradable metals have been pursued most vigorously in the areas of orthopedic implants and cardiovascular stents. In both areas, these devices are needed only for the time necessary for tissue repair and then problems occur if they remain in the body, like tissue irritation, inflammation and contamination. While the US FDA has not approved biodegradable metals as implants to date, Mg metal devices are in clinical use in both Europe and Asia and no significant negative impacts have been observed. Members of the ERC-RMB team, including Dr. Pixley, have taken part in efforts to inform and assist the FDA in considering approval of biodegradable metals for biomedical implants. The use of Zn metal has been a more recent development and preclinical studies are demonstrating that it is safe to use and has significant promise for use in cardiovascular stents. Zn metal and Zn-based alloys have several advantages over Mg and its alloys in terms of tissue repair, so we have now begun exploration of Zn metal implants.
Techniques used in the lab involve animal surgery, behavioral studies and then histological analyses. We also use cell culture to study the cellular responses to the metals, their ions and other degradation products.
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