The advent of biodegradable polymers constituted an important development tool for the realization of modern systems that can be used in biomedicine. Biodegradable polymers are essential when it is necessary to have easily workable materials with suitable properties to obtain an excellent biological response, for this reason they found applications in a wide range of tissue engineering and drug delivery systems. The main limitation of biopolymers is however in the properties of the materials themselves, sometimes too poor compared to the application field in which they need to be used to provide efficient support or therapy. The fabricated systems exposed in this thesis work, aim to provide useful tools not only for the improvement of previously developed polymeric systems but also for the achievement of new objectives in the field of neuronal cultures and controlled drug release. Specifically, Chitosan (CHI) has been used as a bulk material to produce engineered neuronal networks both at the two-dimensional level and, in the currently essential passage towards biologically more relevant models, at the 3D one. Gold nanorods (GNRs) have been used thanks to their good interaction with chitosan to provide thermo-plasmonic properties to a composite ink developed to be able to be printed using a commercial ink-jet printer, with the aim of creating a platform for simple and scalable neuronal networks stimulation for potential studies to better understand brain diseases (such as epilepsy). Moreover, chitosan was used to manufacture porous microparticles by means of air-assisted jetting technique and phase inversion gelation. These systems can be used in various fields such as tissue engineering, as a bottom-up 3D scaffolds, or in drug delivery for local drug release. Precisely in these two directions I worked during my PhD research activity to develop systems that, by using Chitosan as a base, exploited the interactions with other materials to improve the properties of the biopolymer. Interactions between CHI and graphitic materials have been exploited to provide to scaffolds, formed by assemblies of neurons and chitosan microspheres, electrical conductivity, mechanical strength, and degradative resistance in physiological and/or injury conditions. With this in mind, graphite oxide and graphite nanoplatelets were used both as filler and by electrostatic surface interaction, evaluating the different impact on the bulk properties of CHI and on the material-cell interface.Afterwards, with a conservative approach, I used CHI microparticles as a potential carrier for drug release in the gastrointestinal tract. The poor degradative resistance of CHI in harsh conditions made it necessary to apply a surface coating. The biocompatible synthetic polymer already widely used in drug delivery Poly-(styrene-co-maleic anhydride) (PSMA), thanks to the strong grafting reaction with CHI, made it possible to obtain a system with a limited burst effect in the release of molecules in the first hour of administration. The overall findings of this thesis support the efforts in making novel bio-fabricated systems as greatly promising tools for tissue engineering and controlled drug delivery. Specifically, the interaction between biopolymers and synthetic polymers can introduce interesting innovations in the fields of drug delivery, while interactions between biopolymers and carbon-based materials could be a key point for the next years perspective in neuro-engineering.

Engineered biopolymeric systems for tissue engineering and drug delivery applications

ARNALDI, PIETRO
2022-07-20

Abstract

The advent of biodegradable polymers constituted an important development tool for the realization of modern systems that can be used in biomedicine. Biodegradable polymers are essential when it is necessary to have easily workable materials with suitable properties to obtain an excellent biological response, for this reason they found applications in a wide range of tissue engineering and drug delivery systems. The main limitation of biopolymers is however in the properties of the materials themselves, sometimes too poor compared to the application field in which they need to be used to provide efficient support or therapy. The fabricated systems exposed in this thesis work, aim to provide useful tools not only for the improvement of previously developed polymeric systems but also for the achievement of new objectives in the field of neuronal cultures and controlled drug release. Specifically, Chitosan (CHI) has been used as a bulk material to produce engineered neuronal networks both at the two-dimensional level and, in the currently essential passage towards biologically more relevant models, at the 3D one. Gold nanorods (GNRs) have been used thanks to their good interaction with chitosan to provide thermo-plasmonic properties to a composite ink developed to be able to be printed using a commercial ink-jet printer, with the aim of creating a platform for simple and scalable neuronal networks stimulation for potential studies to better understand brain diseases (such as epilepsy). Moreover, chitosan was used to manufacture porous microparticles by means of air-assisted jetting technique and phase inversion gelation. These systems can be used in various fields such as tissue engineering, as a bottom-up 3D scaffolds, or in drug delivery for local drug release. Precisely in these two directions I worked during my PhD research activity to develop systems that, by using Chitosan as a base, exploited the interactions with other materials to improve the properties of the biopolymer. Interactions between CHI and graphitic materials have been exploited to provide to scaffolds, formed by assemblies of neurons and chitosan microspheres, electrical conductivity, mechanical strength, and degradative resistance in physiological and/or injury conditions. With this in mind, graphite oxide and graphite nanoplatelets were used both as filler and by electrostatic surface interaction, evaluating the different impact on the bulk properties of CHI and on the material-cell interface.Afterwards, with a conservative approach, I used CHI microparticles as a potential carrier for drug release in the gastrointestinal tract. The poor degradative resistance of CHI in harsh conditions made it necessary to apply a surface coating. The biocompatible synthetic polymer already widely used in drug delivery Poly-(styrene-co-maleic anhydride) (PSMA), thanks to the strong grafting reaction with CHI, made it possible to obtain a system with a limited burst effect in the release of molecules in the first hour of administration. The overall findings of this thesis support the efforts in making novel bio-fabricated systems as greatly promising tools for tissue engineering and controlled drug delivery. Specifically, the interaction between biopolymers and synthetic polymers can introduce interesting innovations in the fields of drug delivery, while interactions between biopolymers and carbon-based materials could be a key point for the next years perspective in neuro-engineering.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11567/1090662
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