Catalytic and bioactive nanostructures for regenerative medicine applications

Abstract

Peptide nanostructures provide a remarkable toolbox for designing nature inspired smart materials. Synthetic peptide nanomaterials can be tailored with chemical, physical and biological signals to be utilized in a wide range of applications in biomedicine. With the increasing demand for complex nanostructures with facile preparation methods, bioinspired smart nanomaterials have gained more importance for achieving multifunctional hybrid materials. In particular, biological or chemical cues can be integrated into supramolecular designs to generate bioactive materials. This thesis describes nature inspired combinatorial methods for designing peptide nanostructures, which display catalytic and biologically functional moieties. These multifunctional peptide nanostructures were synthesized by using solid phase peptide synthesis. Designed peptide units were in accordance with the relevant biological function and they self-assemble to form nanofibrous networks mimicking the extracellular matrix. This combinatorial approach allows a wide range of applications including artificial catalysis, cell cultivation, biomineralization and live-cell labeling. In this thesis, the self-assembled catalytic and bioactive peptide nanostructures were utilized in artificial enzyme studies, biomineralization and tissue regeneration. The results show that these new artificial enzymes display both catalytic and biological functions of their natural counterparts such as proteins. In the first chapter, basic concepts of self-assembly, artificial catalysis approach, biomineralization and bioactive peptide nanostructures were explained. In the second chapter, multicomponent artificial catalyst model formed by self-assembly was investigated. Designed artificial peptide molecules were characterized structurally and catalytic capability of this de novo system was shown with both model and actual substrate. In the third chapter, ALP inspired catalytic, ion coordinating and biomineralizable peptide nanostructures were examined, bioactivity of this enzyme inspired materials was shown with multiple cell lines and using 2D and 3D cell culture methods. In the fourth chapter, enzyme responsive dentin sialophospho-protein like materials were exhibited instead artificial catalyst. Multi-responsive material induced biomineralization similar to dentin sialophospho-protein which controls mineralization during dentinogenesis. In the fifth part, peptide nanostructures were applied as bioorthogonal catalyst for live-cell tagging study, fluorophore tagged living cells by peptide catalyst was imaged by confocal microscopy. The last chapter covers novel materials inspired by unique nature of collagen and its bioregenerative capacity investigated with stem cells and preliminary cartilage induction was obtained.