Among biomimetic molecules, synthetic peptides can be designed to mimic signals starting or regulating biological pathways, in both model systems and to replace non-functional human proteins. Their potential use in regenerative medicine has prompted a redefinition, in this thesis work, of a PROSITE molecular pattern that was previously characterized as the motif shared by a family of proteins involved in guiding, developing, and growing neurons. Through the definition of this new neurite outgrowth and guidance (NOG) motif, it was possible to include, in addition to the family of CAM molecules with Immunoglobulin (Ig)-like domains involved in NOG processes, further proteins with a NOG motif shared by domains different from the Ig-like fold and similarly implicated in the process of neuritogenesis. Through a computational approach based on comparative sequence analysis and structural modeling, it was possible not only to improve the original NOG motif but also to gain insights into the potential interactions among the various molecules involved in the process. In parallel, a hydrogel scaffold composed of self-assembling peptides containing the RGD motif and embedded with carbon nanotubes was developed for mimicking the elastic modulus and electrical conductivity of the extracellular matrix in the nervous system. The human neuroblastoma-derived cell line SH-SY5Y was used as an in vitro model, enabling the study of processes that influence the nervous system and the evaluation of both cell adhesion and biocompatibility after the cells are seeded onto the scaffold. This thesis results open the route to the synthesis of novel biomimetic peptides and to their combination to the newly developed peptide-based hydrogel.

Development of biomimetics and hydrogel scaffolds for use in regenerative medicine

DI MARCO, CLAUDIA
2023/2024

Abstract

Among biomimetic molecules, synthetic peptides can be designed to mimic signals starting or regulating biological pathways, in both model systems and to replace non-functional human proteins. Their potential use in regenerative medicine has prompted a redefinition, in this thesis work, of a PROSITE molecular pattern that was previously characterized as the motif shared by a family of proteins involved in guiding, developing, and growing neurons. Through the definition of this new neurite outgrowth and guidance (NOG) motif, it was possible to include, in addition to the family of CAM molecules with Immunoglobulin (Ig)-like domains involved in NOG processes, further proteins with a NOG motif shared by domains different from the Ig-like fold and similarly implicated in the process of neuritogenesis. Through a computational approach based on comparative sequence analysis and structural modeling, it was possible not only to improve the original NOG motif but also to gain insights into the potential interactions among the various molecules involved in the process. In parallel, a hydrogel scaffold composed of self-assembling peptides containing the RGD motif and embedded with carbon nanotubes was developed for mimicking the elastic modulus and electrical conductivity of the extracellular matrix in the nervous system. The human neuroblastoma-derived cell line SH-SY5Y was used as an in vitro model, enabling the study of processes that influence the nervous system and the evaluation of both cell adhesion and biocompatibility after the cells are seeded onto the scaffold. This thesis results open the route to the synthesis of novel biomimetic peptides and to their combination to the newly developed peptide-based hydrogel.
2023
Development of biomimetics and hydrogel scaffolds for use in regenerative medicine
Pattern-based motif
Biomimetic peptides
Docking simulations
CNT-hydrogels
Regen. Med.
File in questo prodotto:
File Dimensione Formato  
DiMarco_Claudia.pdf

accesso riservato

Dimensione 6.06 MB
Formato Adobe PDF
6.06 MB Adobe PDF

The text of this website © Università degli studi di Padova. Full Text are published under a non-exclusive license. Metadata are under a CC0 License

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12608/79725