Riassunto analitico
Traumatic injuries of the central nervous system (including brain and spinal cord injuries) and peripheral nervous system have a huge impact on people’s health and quality of life, as they often result in partial or complete loss of motor and sensory function. Notably, the therapeutic options currently available to address spinal cord injury are limited to symptomatic treatments or the use of neuroprostheses and brain machine interfaces to stimulate supraspinal locomotor recovery. Unfortunately, none of these treatments has been shown to lead to complete repair of the damaged spinal cord tissue. In this context, one promising strategy is the design of multifunctional biomaterials that can support neuronal growth, polarization and connectivity, ultimately promoting the repair of damaged neural tissue.
In this thesis work, I investigated for the first time the possibility of fabricating biodegradable biomaterials (polylactic acid, PLA, and polylactic-co-glycolic acid, PLGA) featuring a nanomodulated surface topography and endowing them with conductive properties by adding a thin layer of poly(3,4-ethylendioxithiophene) poly(styrene sulphonate) (PEDOT:PSS). Interestingly, both of these two features (i.e. topographic and electrical cues) have been separately demonstrated to be extremely promising in directing neuronal polarization and axonal growth in vitro. However, the synergistic coupling of these two features in the same material has never reported so far.
For this purpose, I combined soft-lithography methods to obtain nanosized grooves with lateral dimensions similar to those of axons, with electrochemical polymerization to deposit a nanostructured conductive layer of PEDOT:PSS on top of the grooves. PEDOT:PSS is an easily processable and biocompatible (semi-)conductive polymer, widely used in organic devices and tissue engineering scaffolds due to its attractive electrical and physicochemical properties, representing an ideal candidate to be interfaced with the underlying biodegradable polyester.
The sample topography, electrochemical and thermal properties were carefully evaluated using a set of characterization techniques, including atomic force microscopy (AFM), electrochemical impedance spectroscopy (EIS), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC).
Another important advance in my work over existing literature devoted to guiding neuronal development is the use of biodegradable polymers as substrates. Indeed, this will allow for a more effective translation of the nanomodulated conductive materials developed in this thesis work into the field of neural tissue engineering, as they are easily incorporated into 3D. With this in mind, I have also conducted preliminary investigations into the possibility to incorporating the developed multifunctional materials within a gelatin-methacryloyl (GelMa) hydrogel, the latter being one of the most studied hydrogel for neural tissue repair.
The results obtained in this work underscored the possibility of pursuing the proposed fabrication pathway to obtain a new platform of biodegradable materials potentially capable to promote neuronal growth and differentiation and neural tissue regeneration, by providing multiple stimuli at the same time, within the same biomaterial.
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Abstract
Traumatic injuries of the central nervous system (including brain and spinal cord injuries) and peripheral nervous system have a huge impact on people’s health and quality of life, as they often result in partial or complete loss of motor and sensory function. Notably, the therapeutic options currently available to address spinal cord injury are limited to symptomatic treatments or the use of neuroprostheses and brain machine interfaces to stimulate supraspinal locomotor recovery. Unfortunately, none of these treatments has been shown to lead to complete repair of the damaged spinal cord tissue. In this context, one promising strategy is the design of multifunctional biomaterials that can support neuronal growth, polarization and connectivity, ultimately promoting the repair of damaged neural tissue.
In this thesis work, I investigated for the first time the possibility of fabricating biodegradable biomaterials (polylactic acid, PLA, and polylactic-co-glycolic acid, PLGA) featuring a nanomodulated surface topography and endowing them with conductive properties by adding a thin layer of poly(3,4-ethylendioxithiophene) poly(styrene sulphonate) (PEDOT:PSS). Interestingly, both of these two features (i.e. topographic and electrical cues) have been separately demonstrated to be extremely promising in directing neuronal polarization and axonal growth in vitro. However, the synergistic coupling of these two features in the same material has never reported so far.
For this purpose, I combined soft-lithography methods to obtain nanosized grooves with lateral dimensions similar to those of axons, with electrochemical polymerization to deposit a nanostructured conductive layer of PEDOT:PSS on top of the grooves. PEDOT:PSS is an easily processable and biocompatible (semi-)conductive polymer, widely used in organic devices and tissue engineering scaffolds due to its attractive electrical and physicochemical properties, representing an ideal candidate to be interfaced with the underlying biodegradable polyester.
The sample topography, electrochemical and thermal properties were carefully evaluated using a set of characterization techniques, including atomic force microscopy (AFM), electrochemical impedance spectroscopy (EIS), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC).
Another important advance in my work over existing literature devoted to guiding neuronal development is the use of biodegradable polymers as substrates. Indeed, this will allow for a more effective translation of the nanomodulated conductive materials developed in this thesis work into the field of neural tissue engineering, as they are easily incorporated into 3D. With this in mind, I have also conducted preliminary investigations into the possibility to incorporating the developed multifunctional materials within a gelatin-methacryloyl (GelMa) hydrogel, the latter being one of the most studied hydrogel for neural tissue repair.
The results obtained in this work underscored the possibility of pursuing the proposed fabrication pathway to obtain a new platform of biodegradable materials potentially capable to promote neuronal growth and differentiation and neural tissue regeneration, by providing multiple stimuli at the same time, within the same biomaterial.
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