ETD

Archivio digitale delle tesi discusse presso l'Università di Pisa

Tesi etd-02212009-201030


Tipo di tesi
Tesi di dottorato di ricerca
Autore
PUPPI, DARIO
URN
etd-02212009-201030
Titolo
EVALUATION OF BIODEGRADABLE POLYMERIC MATERIALS AS SCAFFOLD IN BONE AND CARTILAGE TISSUE REGENERATION
Settore scientifico disciplinare
CHIM/04
Corso di studi
BIOMATERIALI
Relatori
Relatore Prof. Chiellini, Emo
Parole chiave
  • scaffold
  • electrospinning
  • bioreactors
  • biomaterials
  • tissue engineering
  • wetspinning
Data inizio appello
17/03/2009
Consultabilità
Non consultabile
Data di rilascio
17/03/2049
Riassunto
The present Ph.D. program was carried out within the framework of a project funded by European Network of Excellence (NoE) Expertissues, focused on novel therapeutic strategies for tissue engineering of bone and cartilage. The integrated collaboration established within the international members of the NoE was the driving force of the multidisciplinary plan of the present work, which included many aspects of Biomaterials science and technology, such as technological design, materials processing and chemical-physical characterization, pharmaceutical aspects, and in vitro biological evaluation of the manufacturing products. The research activities reported in the present thesis are the result of experimental works performed at BIOLab of University of Pisa and during visits at hosting institutions of NoE partners, particularly University of Minho (Braga, Portugal), Tampere University of Technology (Tampere, Finland), University of Sheffield (Sheffield, UK), and Chalmers University (Gothenburg, Sweden).
Presently the most common concept underlying tissue engineering is to combine a three-dimensional porous matrix or scaffold, living cells and/or biologically active molecules to form a living construct promoting the repair and regeneration of human tissue. The scaffold supports cell colonization, migration, growth and differentiation, and often guides the development of the required tissue or acts as a drug delivery vehicle.
The aim of the present experimental work was to investigate the preparation and application of biodegradable polymeric microfibrous meshes as scaffold for bone and cartilage tissue regeneration. The development of advanced technologies for materials processing and bioreactor cell culturing, the materials scaffolding and the characterization of the developed scaffolds and tissue constructs were the main objects of the research activities performed during the PhD program .
Three dimensional polymeric fibrous meshes made of both novel and commercial polymers, such as poly(lactic-co-glycolic acid), poly(vinyl alcohol) and star poly(-caprolactone), were developed employing the electrospinning technique, a simple and inexpensive method for the fabrication of ultrafine fibers. For such purpose, an advanced electrospinning apparatus equipped with a dynamic device for the manufacturing of meshes with different fiber assemblies and collection geometries was designed and assembled. Additional drug releasing features were provided by incorporating biologically active agents, such as retinoic acid or clodronate, in the polymeric electrospun scaffolds. The release kinetics of the loaded systems was investigated and correlated to the biodegradation behavior and microstructure of the meshes. Fiber meshes with different structural scale and texture were also developed exploiting the wet spinning technique. Moreover, with the aim of improving scaffold osteoconductivity and mechanical properties, hydroxyapatite nanoparticles were incorporated polymer fibers. The tensile mechanical properties of the produced meshes were analyzed and preliminary biological characterization of the produced meshes were performed to evaluate mesh cytocompatibility, bioactivity of the released agents and influence of mechanical conditioning on growing tissue.
Finally, a dynamic cell culturing system allowing for continuous medium supply and for the employment of different culturing conditions, by employing either a perfusion or a rotating wall chamber was designed and assembled.
The research activity was performed under a multidisciplinary approach and all the described objectives were part of the five main topics that constitute the body of this work:

• Development of Advanced Technologies for Tissue Engineering Applications
• Poly(lactic-co-glycolic acid) Electrospun Fibrous Meshes for the Controlled Release of Retinoic Acid
• Development of Electrospun Fibrous Meshes Based on Partially Hydrolyzed Poly(vinyl alcohol)
• Development of Electrospun Three-arm Star Poly(e-caprolactone) Meshes for Tissue Engineering Application
• Optimized Electrospinning and Wet-spinning Procedures for the Production of Polymeric Fibrous Scaffolds Loaded with Bisphosphonate and Hydroxyapatite

The results attained in PhD plan implementation will constitute the body of an equivalent number of papers to be submitted for publications in journals relevant to Biomaterials & Tissue Engineering.
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