Sensorineural hearing loss (SNHL) is the most common permanent ear disorder affecting people worldwide. The treatment of profound SNHL requires the use of a cochlear implant whose implantation has many disadvantages related to its construction and to quality of life of implanted patient. Thus, scientists are working on innovative cochlear implants to achieve a better hearing sensitivity and quality in deaf population. Another common ear disorder is the perforation of the tympanic membrane. In case of serious perforation, the surgical treatments currently used are the myringoplasty and the tympanoplasty but, both techniques have suboptimal outcome. For this reason, many studies are focused on the creation of scaffolds, to be used in tympanic membrane regeneration. The aim of this thesis was to analyse the in vitro biocompatibility and efficacy of new nanomaterials and biomaterials to be used in the inner and middle ear, for functional recovery or replacement of damaged tissues and cells. Firstly, the biocompatibility of piezoelectric nanoparticles barium titanate and lithium niobate was analysed on two different cell lines, an Organ of Corti cell line (OC-k3) and a neuron-like cell line deriving from rat pheochromocytoma (PC12). These piezoelectric nanoparticles are involved in the construction of an innovative “self-powered” cochlear implant, which, by exploiting its piezoelectric features, will stimulate the cochlear neurons bypassing the damaged inner ear cells. The biocompatibility study was assessed by analysing cytotoxic, apoptotic, oxidative and neurotoxic stimuli. In the second part of the study, the aim was to analyse the biocompatibility of different patches and nanoparticles involved in the construction of biodegradable scaffolds produced using copolymers of poly(ethylene oxide-terephthalate)/poly(butylene terephthalate) (PEOT/PBT), containing chitin nanofibrils (CNs), and covered by different types of nanoparticles loaded with the antibiotic ciprofloxacin. These biocompatible devices aim to facilitate the healing process of the tympanic membrane by improving the proliferation and migration of keratinocytes and by reducing the middle ear inflammation and the incidence of infection during the wound healing process. The biocompatibility was assessed on OC-k3 cells by analysing the cytotoxicity and the morphological changes induced by the PEOT/PBT copolymers containing different (w/w %) weight ratio of CNs: polyethylene glycol (PEG) pre-composite; and of the ciprofloxacin-loaded poly (lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), molecular imprinting (MIPNP) and non-molecular imprinting (NIPNP) nanoparticles. The results showed that barium titanate and lithium niobate did not induce any cytotoxic or apoptotic effects on OC-k3 and PC12 cells, but actually increased cell viability and improved neuritic network. These piezoelectric nanoparticles appear biocompatible for inner ear cells and are good candidates for improving the efficiency of new implantable hearing devices without damaging neurons. Overall, these results confirm that the electric stimulation has neuromodulatory effects on neurons and highlight the importance of developing new scaffolds coated with piezoelectric nanoparticles to be exploited in the treatment of neuronal diseases. Concerning the second part of this project, the results showed the biocompatibility of all materials involved in the production of the biodegradable scaffolds made of the PEOT/PBT copolymers, containing CNs, and covered by ciprofloxacin loaded nanoparticles, on the inner ear cell line OC-k3. Although further tests are required to clarify the effects of these materials, the construction of scaffolds containing chitin nanofibrils and ciprofloxacin-loaded nanoparticles, could be a great advantage for new implantable biodegradable devices to be used for repair of damaged tympanic membrane, without inducing any toxic effects on the delicate inner ear cells.

Sensorineural hearing loss (SNHL) is the most common permanent ear disorder affecting people worldwide. The treatment of profound SNHL requires the use of a cochlear implant whose implantation has many disadvantages related to its construction and to quality of life of implanted patient. Thus, scientists are working on innovative cochlear implants to achieve a better hearing sensitivity and quality in deaf population. Another common ear disorder is the perforation of the tympanic membrane. In case of serious perforation, the surgical treatments currently used are the myringoplasty and the tympanoplasty but, both techniques have suboptimal outcome. For this reason, many studies are focused on the creation of scaffolds, to be used in tympanic membrane regeneration. The aim of this thesis was to analyse the in vitro biocompatibility and efficacy of new nanomaterials and biomaterials to be used in the inner and middle ear, for functional recovery or replacement of damaged tissues and cells. Firstly, the biocompatibility of piezoelectric nanoparticles barium titanate and lithium niobate was analysed on two different cell lines, an Organ of Corti cell line (OC-k3) and a neuron-like cell line deriving from rat pheochromocytoma (PC12). These piezoelectric nanoparticles are involved in the construction of an innovative “self-powered” cochlear implant, which, by exploiting its piezoelectric features, will stimulate the cochlear neurons bypassing the damaged inner ear cells. The biocompatibility study was assessed by analysing cytotoxic, apoptotic, oxidative and neurotoxic stimuli. In the second part of the study, the aim was to analyse the biocompatibility of different patches and nanoparticles involved in the construction of biodegradable scaffolds produced using copolymers of poly(ethylene oxide-terephthalate)/poly(butylene terephthalate) (PEOT/PBT), containing chitin nanofibrils (CNs), and covered by different types of nanoparticles loaded with the antibiotic ciprofloxacin. These biocompatible devices aim to facilitate the healing process of the tympanic membrane by improving the proliferation and migration of keratinocytes and by reducing the middle ear inflammation and the incidence of infection during the wound healing process. The biocompatibility was assessed on OC-k3 cells by analysing the cytotoxicity and the morphological changes induced by the PEOT/PBT copolymers containing different (w/w %) weight ratio of CNs: polyethylene glycol (PEG) pre-composite; and of the ciprofloxacin-loaded poly (lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), molecular imprinting (MIPNP) and non-molecular imprinting (NIPNP) nanoparticles. The results showed that barium titanate and lithium niobate did not induce any cytotoxic or apoptotic effects on OC-k3 and PC12 cells, but actually increased cell viability and improved neuritic network. These piezoelectric nanoparticles appear biocompatible for inner ear cells and are good candidates for improving the efficiency of new implantable hearing devices without damaging neurons. Overall, these results confirm that the electric stimulation has neuromodulatory effects on neurons and highlight the importance of developing new scaffolds coated with piezoelectric nanoparticles to be exploited in the treatment of neuronal diseases. Concerning the second part of this project, the results showed the biocompatibility of all materials involved in the production of the biodegradable scaffolds made of the PEOT/PBT copolymers, containing CNs, and covered by ciprofloxacin loaded nanoparticles, on the inner ear cell line OC-k3. Although further tests are required to clarify the effects of these materials, the construction of scaffolds containing chitin nanofibrils and ciprofloxacin-loaded nanoparticles, could be a great advantage for new implantable biodegradable devices to be used for repair of damaged tympanic membrane, without inducing any toxic effects on the delicate inner ear cells.

Nano ingegnerizzazione dell'orecchio umano / Candito, Mariarita. - (2022 Jun 10).

Nano ingegnerizzazione dell'orecchio umano

CANDITO, MARIARITA
2022

Abstract

Sensorineural hearing loss (SNHL) is the most common permanent ear disorder affecting people worldwide. The treatment of profound SNHL requires the use of a cochlear implant whose implantation has many disadvantages related to its construction and to quality of life of implanted patient. Thus, scientists are working on innovative cochlear implants to achieve a better hearing sensitivity and quality in deaf population. Another common ear disorder is the perforation of the tympanic membrane. In case of serious perforation, the surgical treatments currently used are the myringoplasty and the tympanoplasty but, both techniques have suboptimal outcome. For this reason, many studies are focused on the creation of scaffolds, to be used in tympanic membrane regeneration. The aim of this thesis was to analyse the in vitro biocompatibility and efficacy of new nanomaterials and biomaterials to be used in the inner and middle ear, for functional recovery or replacement of damaged tissues and cells. Firstly, the biocompatibility of piezoelectric nanoparticles barium titanate and lithium niobate was analysed on two different cell lines, an Organ of Corti cell line (OC-k3) and a neuron-like cell line deriving from rat pheochromocytoma (PC12). These piezoelectric nanoparticles are involved in the construction of an innovative “self-powered” cochlear implant, which, by exploiting its piezoelectric features, will stimulate the cochlear neurons bypassing the damaged inner ear cells. The biocompatibility study was assessed by analysing cytotoxic, apoptotic, oxidative and neurotoxic stimuli. In the second part of the study, the aim was to analyse the biocompatibility of different patches and nanoparticles involved in the construction of biodegradable scaffolds produced using copolymers of poly(ethylene oxide-terephthalate)/poly(butylene terephthalate) (PEOT/PBT), containing chitin nanofibrils (CNs), and covered by different types of nanoparticles loaded with the antibiotic ciprofloxacin. These biocompatible devices aim to facilitate the healing process of the tympanic membrane by improving the proliferation and migration of keratinocytes and by reducing the middle ear inflammation and the incidence of infection during the wound healing process. The biocompatibility was assessed on OC-k3 cells by analysing the cytotoxicity and the morphological changes induced by the PEOT/PBT copolymers containing different (w/w %) weight ratio of CNs: polyethylene glycol (PEG) pre-composite; and of the ciprofloxacin-loaded poly (lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), molecular imprinting (MIPNP) and non-molecular imprinting (NIPNP) nanoparticles. The results showed that barium titanate and lithium niobate did not induce any cytotoxic or apoptotic effects on OC-k3 and PC12 cells, but actually increased cell viability and improved neuritic network. These piezoelectric nanoparticles appear biocompatible for inner ear cells and are good candidates for improving the efficiency of new implantable hearing devices without damaging neurons. Overall, these results confirm that the electric stimulation has neuromodulatory effects on neurons and highlight the importance of developing new scaffolds coated with piezoelectric nanoparticles to be exploited in the treatment of neuronal diseases. Concerning the second part of this project, the results showed the biocompatibility of all materials involved in the production of the biodegradable scaffolds made of the PEOT/PBT copolymers, containing CNs, and covered by ciprofloxacin loaded nanoparticles, on the inner ear cell line OC-k3. Although further tests are required to clarify the effects of these materials, the construction of scaffolds containing chitin nanofibrils and ciprofloxacin-loaded nanoparticles, could be a great advantage for new implantable biodegradable devices to be used for repair of damaged tympanic membrane, without inducing any toxic effects on the delicate inner ear cells.
Nano-engineering of the human ear
10-giu-2022
Sensorineural hearing loss (SNHL) is the most common permanent ear disorder affecting people worldwide. The treatment of profound SNHL requires the use of a cochlear implant whose implantation has many disadvantages related to its construction and to quality of life of implanted patient. Thus, scientists are working on innovative cochlear implants to achieve a better hearing sensitivity and quality in deaf population. Another common ear disorder is the perforation of the tympanic membrane. In case of serious perforation, the surgical treatments currently used are the myringoplasty and the tympanoplasty but, both techniques have suboptimal outcome. For this reason, many studies are focused on the creation of scaffolds, to be used in tympanic membrane regeneration. The aim of this thesis was to analyse the in vitro biocompatibility and efficacy of new nanomaterials and biomaterials to be used in the inner and middle ear, for functional recovery or replacement of damaged tissues and cells. Firstly, the biocompatibility of piezoelectric nanoparticles barium titanate and lithium niobate was analysed on two different cell lines, an Organ of Corti cell line (OC-k3) and a neuron-like cell line deriving from rat pheochromocytoma (PC12). These piezoelectric nanoparticles are involved in the construction of an innovative “self-powered” cochlear implant, which, by exploiting its piezoelectric features, will stimulate the cochlear neurons bypassing the damaged inner ear cells. The biocompatibility study was assessed by analysing cytotoxic, apoptotic, oxidative and neurotoxic stimuli. In the second part of the study, the aim was to analyse the biocompatibility of different patches and nanoparticles involved in the construction of biodegradable scaffolds produced using copolymers of poly(ethylene oxide-terephthalate)/poly(butylene terephthalate) (PEOT/PBT), containing chitin nanofibrils (CNs), and covered by different types of nanoparticles loaded with the antibiotic ciprofloxacin. These biocompatible devices aim to facilitate the healing process of the tympanic membrane by improving the proliferation and migration of keratinocytes and by reducing the middle ear inflammation and the incidence of infection during the wound healing process. The biocompatibility was assessed on OC-k3 cells by analysing the cytotoxicity and the morphological changes induced by the PEOT/PBT copolymers containing different (w/w %) weight ratio of CNs: polyethylene glycol (PEG) pre-composite; and of the ciprofloxacin-loaded poly (lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), molecular imprinting (MIPNP) and non-molecular imprinting (NIPNP) nanoparticles. The results showed that barium titanate and lithium niobate did not induce any cytotoxic or apoptotic effects on OC-k3 and PC12 cells, but actually increased cell viability and improved neuritic network. These piezoelectric nanoparticles appear biocompatible for inner ear cells and are good candidates for improving the efficiency of new implantable hearing devices without damaging neurons. Overall, these results confirm that the electric stimulation has neuromodulatory effects on neurons and highlight the importance of developing new scaffolds coated with piezoelectric nanoparticles to be exploited in the treatment of neuronal diseases. Concerning the second part of this project, the results showed the biocompatibility of all materials involved in the production of the biodegradable scaffolds made of the PEOT/PBT copolymers, containing CNs, and covered by ciprofloxacin loaded nanoparticles, on the inner ear cell line OC-k3. Although further tests are required to clarify the effects of these materials, the construction of scaffolds containing chitin nanofibrils and ciprofloxacin-loaded nanoparticles, could be a great advantage for new implantable biodegradable devices to be used for repair of damaged tympanic membrane, without inducing any toxic effects on the delicate inner ear cells.
Nano ingegnerizzazione dell'orecchio umano / Candito, Mariarita. - (2022 Jun 10).
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