Novel functional materials based on self-assembled protein nanofibers (PNNF): Degradation dynamics of PNNFs/hybrid PNNFs and creation of PNNF/hybrid PNNF micro-scaffolds (step 2)

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Due to their outstanding biocompatibility and mechanical strength, protein nanofibers (PNNFs) have a high potential for applications in materials science and biomedical engineering. In this stepwise project (3 project steps with 2 years duration each), we aim towards understanding PNNF formation mechanisms and to apply this knowledge by creating novel PNNF based micro-scaffolds (MS) as building blocks for larger structures in tissue regeneration or drug delivery.In the successfully completed first project step, we i) created novel hybrid PNNFs (hPNNFs) consisting of two different plasma proteins, ii) developed a model for PNNF self-assembly that explains the observed experimental results and allows predictions for new PNNFs, iii) created single PNNFs that are stable in solution for at least 4 weeks, and iv) achieved the desired PNNF mechanical stiffness, leading to publications in high impact factor journals. The results of the first project step lay a promising foundation for the second project step.This second step focuses on the advancement of knowledge of PNNF and MS degradation. It contributes to the future goal of designing the biomaterials’ stability to required regeneration kinetics of tissues. We will test two hypotheses: first, that MSs can be fabricated from PNNFs and novel hybrid PNNFs by layer-by-layer (LBL) with micro-contact printing (μCP) approaches, and second, that based on the understanding of the PNNF degradation, MSs with desired target degradation can be created.Our research aims of project step 2 are, therefore, to i) understand the currently unknown degradation mechanisms of the MSs building blocks (PNNFs/hPNNFs), ii) to apply new strategies to fabricate novel MSs based on the self-assembled PNNFs/hPNNFs.To this end, we will initially investigate the PNNF’s and hPNNF’s degradation dynamics using wet state AFM and QCM considering bone regeneration conditions. The results from these experiments will enable us to understand the PNNF degradation mechanism and the impact of the second protein in hPNNFs and of the PNNF/hPNNF dimensions, which are important for tailoring the degradation of the PNNF/hPNNF based MSs. Next, we will create PNNF/hPNNF based single and bilayers, as important intermediate step to fabricate 3D MSs, using LBL dip coating.Finally, we will create 3D-MSs by combining LBL and μCP approaches with the aim to understand and adjust the MS’ degradation properties through the choice of PNNF/hPNNF dimensions as well as the choice of the MS structure.In the third project step (last 2 years), we will tailor the degradation, mechanical properties and, thus, the cellular response to the MSs.We expect that the projected results will significantly advance the knowledge and understanding of PNNFs and have a considerable impact on the application of MSs as biomaterials for tissue regeneration through the flexibility of the PNNF’s and MS’ properties.