gms | German Medical Science

Question: In the last decades, many attempts have been made to develop efficient strategies for the reconstruction of peripheral nerve injuries. Newly developed biomaterials with a structural and biochemical protective and growth permissive niche for regenerating axons and nerve-glial cells, served as nerve guides. In the scope of this biomimicking-concept, Schwann cells (SC) have been described for their myelinating and axonal growth supportive functions, creating a permissive environment for regenerative processes. Therefore it is reasonable that in some of the pre-clinically tested nerve guide concepts, SC are implemented for their supportive function. In this context it is important to discover and understand the biological processes enabling SC to attach to and proliferate on the biomaterial. We hypothesized that a dynamic activation of diverse cellular mechanisms occurs during these events. A profound understanding of these processes and their dynamics could enable the drug-assisted optimization of SC attachment and proliferation in the future.

Methods and results: In order to identify the dynamic processes involved in SC attachment and proliferation on a biomaterial, we selected a collagen type 1-based nerve guide with pore channels called Perimaix. A biocompatibility with rat SC was already demonstrated. Purified rat SC were cultured on either Perimaix or plates for 1, 3 and 7 days, respectively. Morphological examinations using electron microscopy revealed temporally altered ER structures, an increased presence of lysosomes as well as changed nuclear architecture upon growth of SC on Perimaix. Using unbiased proteome profiling, 1662 rat SC proteins were quantified between the different conditions and time points and evaluated concerning dynamic biochemical alterations occurring on Perimaix and plates. Apart from proteins belonging to the extra cellular matrix, myelination and axonal interactions, proteins involved in cell stress, protein synthesis and quality control/ proteolysis, apoptotic processes and proliferation are temporally regulated.

Conclusion: The identification of special protein clusters that play central roles during attachment and proliferation not only improve the current understanding of nerve biology and function, but also provide possible starting points for the drug-mediated optimization of nerve regeneration.