Preparazione e caratterizzazione di miscele di polimeri naturali e sintetici per applicazioni come materiali biocompatibili e/o a basso impatto ambientale

Il lavoro di tesi è stato rivolto alla produzione e caratterizzazione di materiali con proprietà idonee prevalentemente per applicazioni nel settore biomedicale, in taluni casi considerando, più in generale, il loro utilizzo come plastiche eco-compatibili. Sono state prodotte e caratterizzate tre classi di materiali con caratteristiche di degradabilità in ambiente acquoso: 1) polimeri sintetici a base di policaprolattone (PCL), tra cui due tipi di PCL a diverso peso molecolare, un copolimero a tre blocchi PCL-POE-PCL e una serie di poliuretani (PU) e poliuretani-uree (PUU), sintetizzati in precedenti lavori di tesi; miscele a base di PCL (sia con polimeri naturali sia con un polimero sintetico, il poli(idrossibutirrato-co-idrossivalerato), PHBHV) e miscele tra i polimeri naturali chitosano e gelatina. I materiali sono stati sottoposti ad una caratterizzazione fisico-chimica di utilità generale e ad una specifica caratterizzazione, nella prospettiva di un loro utilizzo nel settore dell’Ingegneria Tissutale. Sono state adoperate diverse tecniche di produzione degli scaffolds, alcune non-convenzionali, come il sistema di deposizione tramite microsiringa (PAM), la sinterizzazione selettiva tramite laser (SLS) e la tecnica di litografia soft (SL), e alcune convenzionali, come l’estrusione di guide cave dal fuso e la filatura di fibre cave da soluzione polimerica. Inizialmente, è stato effettuato uno screening di biocompatibilità dei materiali tra le tre classi di materiali studiate e, con i materiali risultati più adatti per applicazioni nell’Ingegneria Tissutale, sono stati prodotti scaffolds, attraverso le tecniche di microfabbricazione. In una seconda fase del lavoro, sono stati prodotti scaffolds in forma di guide, tramite filatura dal fuso e da soluzione, per impieghi nel settore della rigenerazione neuronale, usando i materiali maggiormente biocompatibili tra quelli studiati. Il lavoro ha approfondito soprattutto l’aspetto delle applicazioni in campo biomedicale anche se la maggiore parte dei materiali oggetto di studio in questo lavoro sono adatti anche per applicazioni come plastiche eco-compatibili

Biomaterials-Enhanced Intranasal Delivery of Drugs as a Direct Route for Brain Targeting

Intranasal (IN) drug delivery is a non-invasive and effective route for the administration of drugs to the brain at pharmacologically relevant concentrations, bypassing the blood–brain barrier (BBB) and minimizing adverse side effects. IN drug delivery can be particularly promising for the treatment of neurodegenerative diseases. The drug delivery mechanism involves the initial drug penetration through the nasal epithelial barrier, followed by drug diffusion in the perivascular or perineural spaces along the olfactory or trigeminal nerves, and final extracellular diffusion throughout the brain. A part of the drug may be lost by drainage through the lymphatic system, while a part may even enter the systemic circulation and reach the brain by crossing the BBB. Alternatively, drugs can be directly transported to the brain by axons of the olfactory nerve. To improve the effectiveness of drug delivery to the brain by the IN route, various types of nanocarriers and hydrogels and their combinations have been proposed. This review paper analyzes the main biomaterials-based strategies to enhance IN drug delivery to the brain, outlining unsolved challenges and proposing ways to address them

Zein as a renewable material for the preparation of green nanoparticles for drug delivery

Environmental sustainability is a key challenge driven by the increased consumption of natural resources with limited availability. In this scenario agriculture has emerged as a privileged source of renewable resources, hence more efforts should be addressed to the study of plant-derived materials for medical applications. Zein is a biocompatible, biodegradable and amphiphilic prolamin protein extracted from the endosperm tissue of corn. For these reasons, its applications span from coatings for edible capsules, to the fabrication of bi- and tridimensional scaffolds for tissue engineering, and to develop drug delivery systems. This review aims at describing the properties and main applications of zein with a focus on the most recent and updated state of the art literature on zein based nanoparticles for the controlled delivery of various drugs. The main focus is to analyze the state of the art literature to understand how to implement sustainable methods for the preparation of zein NPs and to propose their exploitation as novel drug delivery systems for multiple applications, including oligonucleotide delivery. Main methods for zein NP preparation are described under an ecofriendly point of view, highlighting their environmental sustainability based on used solvents, waste products and energy consumption

approaching 3r teaching in biomedical engineering

Since its adhesion to Centro3R, Politecnico di Torino has approached 3R teaching through a new Master course, entitled "New advances in alternative preclinical trials". This is a multidisciplinary optional course for Master students in Biomedical Engineering, with the contribution of different teachers, who are experts on different aspects of preclinical testing of biomedical devices: European Standards for preclinical experimentation; preclinical animal models; protection of animal welfare in the European legislation; the role of statistics on the application of the 3R principle; preclinical experimental models in vitro; in silico models. This contribution describes the subjects faced by the course and their importance in the context of the 3R Principle

Direct Reprogramming of Adult Human Cardiac Fibroblasts into Induced Cardiomyocytes Using miRcombo

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) through microRNAs (miRNAs) is a new emerging strategy for myocardial regeneration after ischemic heart disease. Previous studies have reported that murine fibroblasts can be directly reprogrammed into iCMs by transient transfection with four miRNAs (miRs-1, 133, 208 and 499 – termed “miRcombo”). While advancement in the knowledge of direct cell reprogramming molecular mechanism is in progress, it is important to investigate if this strategy may be translated to humans. Recently, we demonstrated that miRcombo transfection is able to induce direct reprogramming of adult human cardiac fibroblasts (AHCFs) into iCMs. Although additional studies are needed to achieve iCM maturation, our early findings pave the way toward new therapeutic strategies for cardiac regeneration in humans. This chapter describes methods for inducing direct reprogramming of AHCFs into iCMs through miRcombo transient transfection, showing experiments to perform for assessing iCM generatio

Scaffold functionalization to support a tissue biocompatibility

The aim of this chapter is to illustrate the most applied methods for covalent and non-covalent functionalization of scaffold surface with biomimetic molecules, including bioactive proteins, peptides, and polysaccharides to improve scaffold biocompatibility. Additionally, the main techniques for surface physicochemical characterization are presented together with the commonly used approaches for in vitro testing of biocompatibility. Finally, new perspectives in scaffold surface functionalization and application of functionalized scaffolds are discussed in the conclusions