Tesi etd-04192017-145343
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Tipo di tesi
Perfezionamento
Autore
IACOVACCI, VERONICA
URN
etd-04192017-145343
Titolo
Smart magnetic microsystems for targeted therapy
Settore scientifico disciplinare
ING-IND/34
Corso di studi
INGEGNERIA - Biorobotics
Commissione
relatore Dott. RICOTTI, LEONARDO
Parole chiave
- magnetic micosystems
- magnetic retrieval
- microrobotics
- targeted therapy
Data inizio appello
21/06/2017;
Disponibilità
completa
Riassunto analitico
Recent advancements in diagnostics have led to early stage detection of many pathologies, potentially paving the way to an earlier and more effective treatment of several life-threatening diseases. Despite significant steps ahead in the past decades both in the field of minimally invasive surgery and in pharmacology, with the development of more and more sophisticated instrumentation and drug formulations, respectively, there is still a significant gap between diagnosis and therapy, at present.
Merging competencies derived from robotics, bioengineering and materials science can help in moving forward in this research endeavor, aiming at filling such gap by developing enabling technologies, components and platforms capable of treating many pathologies in the human body, even in hard-to-reach areas.
In this framework, the dream is to develop therapeutic strategies enabling both the treatment of pathologies incurable with currently available tools and to improve existing treatments, making them more efficient and reducing their burden to healthy tissues, thus enhancing their therapeutic index.
This thesis explores novel microsystems that aim to overcome some of the limitations featuring current therapeutic paradigms, based on systemic administration, as well as traditionally proposed nanomedicine strategies that suffer from low controllability. To this aim, the main focus is on solutions at the milli- and the micro-scale, which potentially allow to access all human body districts by exploiting the wide network of natural body lumens and endoluminal accesses. Furthermore, a specific attention has been paid to systems controllable through magnetic fields, a paradigm that has been exploited to enhance microsystems controllability.
The thesis is organized in six Chapters and two Appendices (Figure 1). Although the different devices reported in the different chapters are sometimes not much related to each other (each system is not an evolution of the one reported in the previous chapter), it is possible anyhow to identify a connecting thread among them, thus considering each chapter a step forward in the pathway towards filling the gap among diagnostics and therapy.
Chapter 1 reports the motivation of the whole thesis, a general background concerning therapeutic strategies, microrobotics and triggerable systems for medical applications and the full outline of the thesis. Chapter 2 deals with the fabrication, the magnetic and morphological characterization and the biological assessment of novel magnetic composite materials, developed in the form of thin films, which may enable to overcome the limitations of current magnetic microsystems and that could be eligible for a wide variety of MEMS and biomedical microdevices. Appendix A adds theoretical considerations on magnetic materials properties and characterization, thus supporting the design considerations reported in Chapter 2 and all over the thesis. Chapter 3 and 4 report the design, fabrication and testing of a milli- and microrobot, respectively, devised for targeted drug delivery in the human body. The system described in Chapter 3 is a triggerable bi-component magnetic millirobot for targeted drug delivery, devised for operation in relatively high diameter body canals and based on the superposition of different magnetic effects enabling both its controlled locomotion and the activation of the drug release mechanism. In Chapter 4, a shape-switching microrobot responsive to magnetic fields and to near infrared radiation is reported. Fabrication and controlled drug delivery modulated by shape changes were validated at different scales. Chapter 4 also deals with a challenge that typically affects microrobots for medical applications, namely how to perform a proper in vivo imaging. To this aim, proper microrobot structure modifications and SPECT imaging (whose working principles are clarified in Appendix B) are reported both in vitro and ex vivo.
Chapter 5 reports a novel paradigm potentially able to revolutionize targeted cancer therapy. The proposed solution faces the issue of reducing the severe side effects that are normally produced by high doses of therapeutics or therapeutic agents featured by high treatment efficacy but at the same time high toxicity to healthy tissues. Such solution is an intravascular microdevice able to efficiently retrieve magnetic therapeutic nanovectors not contributing to therapy from the bloodstream. The device concept is described and the system design and in vitro testing are reported.
Finally, Chapter 6 sketches out the conclusions of this study and some future perspectives, highlighting possible routes and strategies to address scientific and clinical issues still hampering the wide adoption of micro and nanosystems in the clinical practice.
Merging competencies derived from robotics, bioengineering and materials science can help in moving forward in this research endeavor, aiming at filling such gap by developing enabling technologies, components and platforms capable of treating many pathologies in the human body, even in hard-to-reach areas.
In this framework, the dream is to develop therapeutic strategies enabling both the treatment of pathologies incurable with currently available tools and to improve existing treatments, making them more efficient and reducing their burden to healthy tissues, thus enhancing their therapeutic index.
This thesis explores novel microsystems that aim to overcome some of the limitations featuring current therapeutic paradigms, based on systemic administration, as well as traditionally proposed nanomedicine strategies that suffer from low controllability. To this aim, the main focus is on solutions at the milli- and the micro-scale, which potentially allow to access all human body districts by exploiting the wide network of natural body lumens and endoluminal accesses. Furthermore, a specific attention has been paid to systems controllable through magnetic fields, a paradigm that has been exploited to enhance microsystems controllability.
The thesis is organized in six Chapters and two Appendices (Figure 1). Although the different devices reported in the different chapters are sometimes not much related to each other (each system is not an evolution of the one reported in the previous chapter), it is possible anyhow to identify a connecting thread among them, thus considering each chapter a step forward in the pathway towards filling the gap among diagnostics and therapy.
Chapter 1 reports the motivation of the whole thesis, a general background concerning therapeutic strategies, microrobotics and triggerable systems for medical applications and the full outline of the thesis. Chapter 2 deals with the fabrication, the magnetic and morphological characterization and the biological assessment of novel magnetic composite materials, developed in the form of thin films, which may enable to overcome the limitations of current magnetic microsystems and that could be eligible for a wide variety of MEMS and biomedical microdevices. Appendix A adds theoretical considerations on magnetic materials properties and characterization, thus supporting the design considerations reported in Chapter 2 and all over the thesis. Chapter 3 and 4 report the design, fabrication and testing of a milli- and microrobot, respectively, devised for targeted drug delivery in the human body. The system described in Chapter 3 is a triggerable bi-component magnetic millirobot for targeted drug delivery, devised for operation in relatively high diameter body canals and based on the superposition of different magnetic effects enabling both its controlled locomotion and the activation of the drug release mechanism. In Chapter 4, a shape-switching microrobot responsive to magnetic fields and to near infrared radiation is reported. Fabrication and controlled drug delivery modulated by shape changes were validated at different scales. Chapter 4 also deals with a challenge that typically affects microrobots for medical applications, namely how to perform a proper in vivo imaging. To this aim, proper microrobot structure modifications and SPECT imaging (whose working principles are clarified in Appendix B) are reported both in vitro and ex vivo.
Chapter 5 reports a novel paradigm potentially able to revolutionize targeted cancer therapy. The proposed solution faces the issue of reducing the severe side effects that are normally produced by high doses of therapeutics or therapeutic agents featured by high treatment efficacy but at the same time high toxicity to healthy tissues. Such solution is an intravascular microdevice able to efficiently retrieve magnetic therapeutic nanovectors not contributing to therapy from the bloodstream. The device concept is described and the system design and in vitro testing are reported.
Finally, Chapter 6 sketches out the conclusions of this study and some future perspectives, highlighting possible routes and strategies to address scientific and clinical issues still hampering the wide adoption of micro and nanosystems in the clinical practice.
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