Development, production, and prediction of fibroin-based degradable implants
Isella, Benedetta
Isella, Benedetta
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Publication Date
2024-10-01
Type
doctoral thesis
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Abstract
Silk fibroin is a protein extracted from silk that exhibits excellent biocompatibility, high mechanical properties, while also being bioabsorbable, which makes it an excellent candidate as a sustainable constituent material of biomedical devices. However, the use of silk fibroin as an implantable material remains limited due to distinct challenges that are encountered during its processing phase, particularly in industrial setting where reproducibility remains an issue and
it can be difficult to produce complex structures. Indeed, several methods have been proposed to fabricate silk fibroin components, among which dip-coating is particularly promising given its versatility and scalability. Using a dip-coating process, there is potential to develop new techniques to obtain stand-alone silk fibroin structures, which could be applied for different scopes in the biomedical field. However, there is a general lack of understanding of the adhesion
mechanisms of silk fibroin during dip-coating and distinct challenges during post-processing steps when trying to isolate the material from the underlying substrate, which usually is performed with the use of additional surfactants possibly impacting the mechanical properties of the structures obtained. The objective of this thesis is to investigate dip-coating techniques as a scalable process for the production of silk fibroin coatings and stand-alone devices, in the form
of tubular structures that have potential application in endoluminal settings. Furthermore, a computational model able to describe the phenomenon of enzymatic degradation is developed to aid in the design process.
In this thesis, a dip-coating layer-by-layer deposition technique is used firstly to investigate the adhesion properties of aqueous silk fibroin to different metallic substrates. The dip-coating process is then optimised and several technical strategies are established to coat irregular medical implants specimens on both hard and soft substrates for dentistry and hernia applications, respectively. The silk-fibroin dip-coating process is then further exploited to enable the production of stand-alone tubular structures for endoluminal applications. This technique involves a multi-layer deposition process on Teflon mandrels and uses an innovative removal process based on water vapor annealing, which offers the possibility of combining the dip-coated layer to other processing techniques or to additional materials. The process is upscaled and applied to applications in the fields of biliary and oesophageal stenting, and the process is further optimised to produce vascular grafts with higher mechanical compliance by the combination of silk fibroin and elastin-like recombinamers (ELRs). Finally, a computational finite-element model was implemented to describe the different steps that characterise the enzymatic degradation of silk fibroin in a scaffold structure. The results showed that dip-coating achieved tightly adhered silk fibroin coatings on both magnesium and titanium substrates and highlighted that the coating adhesion strength was not only dependent on the roughness of the substrate, but also on other material properties such as hydrophilicity and electrode potential. The dip-coating technique also proved effective in coating several medical devices, with the process achieving a barrier layer or an open-porous structure depending on the requirements of the specific application. By applying the technique to Teflon substrates, reproducible and homogeneous tubular structures were obtained for endoluminal applications. In this work, it was shown that by the combination with an electrospun layer the silk fibroin devices were promising for biliary stenting applications, while the integration with a magnesium braided stent allowed to achieve a fully resorbable oesophageal stent. The dip-coating technique was also successful in obtaining, in a single-step, a double network between silk fibroin and ELRs. This enabled, for the first time, the production of silk-fibroin and ELR structures through dip-coating, with extensive mechanical testing demonstrating that this device fulfilled the requirements of mechanical stability and compliance, needed by small-diameter vascular
grafts. Finally, the computational model considering the enzymatic degradation correctly predicted the mass loss of silk fibroin scaffolds both in vitro and in vivo, revealing important considerations for the device design. Overall, this thesis provides significant technical advances and enhances the scientific understanding of the mechanical behaviour of dip-coated silk fibroin-based devices, which could see their more widespread implementation and further research in this area.
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Publisher
University of Galway
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Attribution-NonCommercial-NoDerivatives 4.0 International