The design and application of bionanotechnologies aimed at the nervous system provide powerful new approaches for studying cell and molecular biology and physiology. The successful and development of bionanotechnologies designed to interact with the nervous system as research or clinical tools requires an understanding of the relevant neurophysiology and neuropathology, and an understanding of the relevant chemistry and materials science and engineering. Materials designed molecularly for regeneration of tissues are becoming of great interest in advanced medicine and improvements in the understanding of self-assembly process offer new opportunities in molecular design of biomaterials for vary applications. In this project, two classes of biomaterials were studied with the same final achievement: the application to the regeneration of nervous systems. RADA16-I (AcN-RADARADARADARADA-CNH2), representative of a class of self-assembling peptides with alternate hydrophobic and hydrophilic residues, self-assembles into β-sheet bilayer filaments. Though molecular studies for this class of peptides has been recently developed, new investigations are required to explain how RADA16-I functionalization with biological active motifs, may influence the self-assembling tendency of new functionalized peptides (FP). Since FPs recently became a promising class of biomaterials, a better understanding of the phenomenon is necessary to design new scaffolds for cell biology and nanobiomedical applications. The first part of this project was based on the investigation with computational and experimental tools about the self-assembly of different FPs showing diverse sequences and "in vitro" behaviors. For the first time spectroscopic techniques (Raman and ATR/FTIR) was applied to these class of peptides and new vibrational modes were used to describe the nanostructure. Thanks to molecular dynamic simulations it was possible increase the experimental findings. The functionalizing self-assembling peptides can strongly influence or prevent assembly into nanostructure. Moreover the designing strategies were enhanced thanks to a deep investigation about the Glicines hinge between self assembling core and biological functionalization. The study of this structural group involved a refinement of a functionalized self-assembling peptide with the direct application on neural stem cells, and a then a future in vivo application. In the second part of this project electrospun tubes, formed by micro and nanofibers, were used to regenerate a 10-mm nerve gap in rat sciatic nerve in vivo. This work provided evidence that electrospun micro- and nanofiber PCL/PLGA channels are promising bioabsorbable scaffolds for stimulating and guiding peripheral nerve regeneration in rat models of sciatic nerve transection. This nanotechnological approach shows very encouraging results in peripheral nervous system regeneration that can ameliorate with surgery shrewdness, rehabilitative training and biomaterial modification, or better a combination of both eletrospun and self-assembling fibers. Finally in this project it was shown how a deeply investigation about self-assembling process, starting from theoretical part, could be applied directly in the development of many new biomaterials for specific nanobiomedical applications with the hope of increasing of the application range.
|Data di pubblicazione:||17-dic-2009|
|Titolo:||Computational and experimental characterization of self-assembling peptides for nanobiomedical applications|
|Settore Scientifico Disciplinare:||ING-IND/22 - SCIENZA E TECNOLOGIA DEI MATERIALI|
|Corso di dottorato:||NANOSTRUTTURE E NANOTECNOLOGIE - 33R|
|Citazione:||(2009). Computational and experimental characterization of self-assembling peptides for nanobiomedical applications. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2009).|
|Parole Chiave:||Biomaterials, neural stem cell|
|Appare nelle tipologie:||07 - Tesi di dottorato Bicocca post 2009|