Scaffolds for tissue engineering are expected to respond to a challenging combination of physical, mechanical and biological requirements, guiding the research towards the development of novel hybrid materials and the use of unconventional biofabrication processes. In fact, composite systems can bring together the advantages of their constituent materials, while advanced techniques such as additive manufacturing and electrospinning can produce complex architected and fibrous structures to address the reconstruction of specific biological tissues. This study introduces innovative bioresorbable scaffolds presenting a core-shell structure, in which a 3D-printed polymeric core is meant to ensure temporary mechanical support, while a bioactive hydrogel shell is incorporated to provide a better environment for cell adhesion and proliferation. Thanks to the versatility of the core-shell design and of additive manufacturing, the scaffold properties can be tailored by properly designing the 3D-printed core structure and the core/shell ratio, based on the target application and on patient anatomy. Special attention is dedicated to the case of bone tissue regeneration, here addressed by developing core-shell scaffolds in which a stiff poly(lactic acid) (PLA) lattice structure is grafted with an osteogenic gelatin-chitosan hydrogel. The first chapter provides an introduction to biomaterials and biofabrication techniques employed in the field of tissue engineering, with particular focus on bone and cartilage regeneration, on scaffold property tunability and modeling, and on innovative smart polymeric composites. Thereafter, the experimental work on core-shell composite scaffolds is described in detail, first exploring the tunability of their mechanical properties and hydrogel content by considering a vast set of variables (Chapter 2), and then focusing on the possibility to address bone regeneration with PLA-hydrogel scaffolds, which were subjected to hydrolytic degradation and in vitro experiments and finally tailored for in vivo studies in a rabbit animal model (Chapter 3). These preclinical tests aim at investigating potential translational applications in bone regenerative medicine (Chapter 4). In addition to these experimental studies, approaches based on analytical equations, semi-empirical models, artificial neural networks and numerical simulations are presented as tools for predicting the mechanical properties of scaffold core structures (Chapter 5). Finally, a novel fabrication method to produce tunable polymeric composites capable of reversible shapeshifting is reported, envisioning future scaffold applications such as smart drug release or dynamic mechanical stimulation of cell cultures (Chapter 6).
Gli scaffold per l'ingegneria tissutale sono tenuti a rispondere a un’impegnativa combinazione di requisiti fisici, meccanici e biologici, che orientano la ricerca verso lo sviluppo di nuovi materiali ibridi e l'utilizzo di processi di biofabbricazione non convenzionali. Infatti, i sistemi compositi permettono di coniugare i vantaggi dei materiali che li compongono, mentre tecniche avanzate come la fabbricazione additiva (additive manufacturing) e l'elettrofilatura (electrospinning) sono in grado di produrre strutture complesse fibrose e ad architettura controllata per affrontare la ricostruzione di specifici tessuti biologici. Questo studio introduce innovativi scaffold bioriassorbibili che presentano una struttura core-shell, in cui un nucleo (core) polimerico stampato in 3D ha lo scopo di garantire un supporto meccanico temporaneo, mentre un guscio (shell) di idrogelo bioattivo è incorporato per offrire un miglior ambiente per l'adesione e la proliferazione delle cellule. Grazie alla versatilità della progettazione core-shell e della fabbricazione additiva, le proprietà dello scaffold possono essere personalizzate attraverso un’opportuna progettazione della struttura del core stampato in 3D e del rapporto core/shell, in base all'applicazione designata e all'anatomia del paziente. Particolare attenzione è dedicata al caso della rigenerazione del tessuto osseo, qui affrontato sviluppando scaffold core-shell in cui una rigida struttura reticolare (lattice) di acido polilattico (PLA) è innestata con un idrogelo osteogenico a base di gelatina e chitosano. Il primo capitolo fornisce un'introduzione ai biomateriali e alle tecniche di biofabbricazione utilizzate nel campo dell'ingegneria tissutale, con particolare enfasi sulla rigenerazione dell'osso e della cartilagine, sulla modulazione e modellizzazione delle proprietà degli scaffold e su innovativi compositi polimerici intelligenti. In seguito, viene descritto in dettaglio il lavoro sperimentale sugli scaffold compositi core-shell, esplorando inizialmente la possibilità di modulare le loro proprietà meccaniche e il contenuto di idrogelo considerando un ampio insieme di variabili (Capitolo 2), per poi concentrarsi sulla possibilità di affrontare la rigenerazione dell'osso con scaffold di PLA-idrogelo, che sono stati sottoposti a esperimenti di degradazione idrolitica e in vitro e infine customizzati ai fini di studi in vivo in un modello animale di coniglio (Capitolo 3). Questi test preclinici mirano a studiare le potenziali applicazioni traslazionali nella medicina rigenerativa dell'osso (Capitolo 4). Oltre a questi studi sperimentali, vengono presentati approcci basati su equazioni analitiche, modelli semi-empirici, reti neurali artificiali e simulazioni numeriche come strumenti per la previsione delle proprietà meccaniche delle strutture core degli scaffold (Capitolo 5). Infine, viene presentato un nuovo metodo di fabbricazione per produrre compositi polimerici modulabili in grado di cambiare forma in modo reversibile, con la prospettiva di future applicazioni per gli scaffold, come il rilascio intelligente di farmaci o la stimolazione meccanica dinamica di colture cellulari (Capitolo 6).
Development of Tunable Core-Shell Composite Scaffolds for Tissue Engineering
PASINI, Chiara
2024
Abstract
Scaffolds for tissue engineering are expected to respond to a challenging combination of physical, mechanical and biological requirements, guiding the research towards the development of novel hybrid materials and the use of unconventional biofabrication processes. In fact, composite systems can bring together the advantages of their constituent materials, while advanced techniques such as additive manufacturing and electrospinning can produce complex architected and fibrous structures to address the reconstruction of specific biological tissues. This study introduces innovative bioresorbable scaffolds presenting a core-shell structure, in which a 3D-printed polymeric core is meant to ensure temporary mechanical support, while a bioactive hydrogel shell is incorporated to provide a better environment for cell adhesion and proliferation. Thanks to the versatility of the core-shell design and of additive manufacturing, the scaffold properties can be tailored by properly designing the 3D-printed core structure and the core/shell ratio, based on the target application and on patient anatomy. Special attention is dedicated to the case of bone tissue regeneration, here addressed by developing core-shell scaffolds in which a stiff poly(lactic acid) (PLA) lattice structure is grafted with an osteogenic gelatin-chitosan hydrogel. The first chapter provides an introduction to biomaterials and biofabrication techniques employed in the field of tissue engineering, with particular focus on bone and cartilage regeneration, on scaffold property tunability and modeling, and on innovative smart polymeric composites. Thereafter, the experimental work on core-shell composite scaffolds is described in detail, first exploring the tunability of their mechanical properties and hydrogel content by considering a vast set of variables (Chapter 2), and then focusing on the possibility to address bone regeneration with PLA-hydrogel scaffolds, which were subjected to hydrolytic degradation and in vitro experiments and finally tailored for in vivo studies in a rabbit animal model (Chapter 3). These preclinical tests aim at investigating potential translational applications in bone regenerative medicine (Chapter 4). In addition to these experimental studies, approaches based on analytical equations, semi-empirical models, artificial neural networks and numerical simulations are presented as tools for predicting the mechanical properties of scaffold core structures (Chapter 5). Finally, a novel fabrication method to produce tunable polymeric composites capable of reversible shapeshifting is reported, envisioning future scaffold applications such as smart drug release or dynamic mechanical stimulation of cell cultures (Chapter 6).File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14242/70086
URN:NBN:IT:UNIBS-70086