DESIGN OF VASCULARIZABLE SCAFFOLDS FOR LARGE TISSUE ENGINEERING

The emerging field of tissue engineering is dedicated to restore, maintain or improve the functions of damaged or lost human tissues. However, despite significant successes have been achieved over the last 20 years, several challenges still remain, preventing a pervasive clinical application of tissue engineering. One of the main challenges lies in the development of scaffolding materials able to mimic the complex organization of the in vivo milieu and provide tailored stimuli for tissue growth and maturation. A fundamental aspect of this problem resides in the design of scaffolds having three-dimensional vascular architecture, able to provide optimal nutrients diffusion, supporting and maintaining viable tissue in vitro, and capable to promote vascularization after implantation. The lack of proper vascularization is currently limiting the size of the engineered tissues to smaller than clinically relevant dimensions. The aim of this PhD work, merging the study of novel biomaterials and the development of original microfabrication methods, is to create enabling technologies towards the design of innovative scaffolds for large tissues engineering. For this purpose, a library of RGD-mimetic hydrogels with controlled chemical, mechanical and biological features has been developed. The obtained hydrogels have been combined with foaming and sacrificial molding techniques to engineer customizable scaffolds with hierarchical three-dimensional architectures. These novel hydrogel scaffolds supported optimal three-dimensional cell growth and promoted in vitro vascularization in large constructs. The reported results suggest that the presented approach could represent a viable solution to scale engineered tissue to clinically relevant dimensions releasing the full potential of regenerative medicine

Polymer Processing and Surfaces

This book focuses on fundamental and applied research on polymer processing and its effect on the final surface as the optimization of polymer surface properties results in the unique applicability of these over other materials. The development and testing of the next generation of polymeric and composite materials is of particular interest. Special attention is given to polymer surface modification, external stimuli-responsive surfaces, coatings, adhesion, polymer and composites fatigue analysis, evaluation of the surface quality and microhardness, processing parameter optimization, characterization techniques, among others

Development of electrospun multifunctional fibrous structures for icephobic and superhydrophobic applications

Icephobicity is defined as the ability of a solid surface to prevent ice accumulation or the potential of repelling ice from the surface. On the other hand, superhydrophobicity is a physical property of a surface, which means lacking affinity for water, and tending to repel water. Although these two surface properties have critical application areas such as energy harvesting systems, transportation, corrosion resistance coatings and friction reduction, fabricating superhydrophobic and icephobic surfaces is still a big challenge due to the lack of scalable, straightforward, and cost-effective production methods. Moreover, integrating additional functions, including electromagnetic interference (EMI) shielding and electrical conductivity to these materials to achieve multifunctionality, enables many modern applications, such as EMI shielding protective devices and power transmission systems. Electrospinning is one of the most commonly used methods to produce nano-sized polymeric fibrous membranes or coatings. Unique properties such as high surface-to-volume ratio, high porosity interconnected open pore structures, and adjustable pore sizes make electrospun membranes irreplaceable. However, the potential of using the electrospinning method to produce superhydrophobic and icephobic surfaces is still not investigated in depth. Although there are some studies on the superhydrophobic application of electrospun membranes, considerable challenges remain, such as expensive chemicals, low reproducibility, complex production techniques, and the necessity of a post-treatment or functionalization step. Moreover, electrospun membranes may be a good candidate for icephobic applications based on the Cassie-Baxter icing state or specific material design such as slippery liquid-infused porous structures (SLIPS). In the Cassie-Baxter icing state, water does not penetrate the details of roughness but sits on the air pockets, which provides a low icing area between the ice and the surface, resulting in a lowered work of adhesion of ice. However, no report has been found that explores the potential of the electrospinning method for icephobic applications. In this thesis, the potential of using electrospinning method to fabricate superhydrophobic and icephobic surfaces has been explored. Polyvinylidene fluoride-co-hexafluoropropylene (PVDF-co-HFP), which is a low surface energy polymer, was used to explore the potential of using electrospinning method to design a one-step production method of superhydrophobic surfaces without a post-treatment or nanofiller by only changing the production parameters of electrospinning. The proposed method has significant benefits such as shortened processes, less material use, and low-cost production compared to multistep methods reported in the literature. Moreover, the roles of each parameter on surface topography, contact angle, and fibre formation have been discussed. Superhydrophobicity has been achieved thanks to the synergetic effect of the roughness and the low surface tension of the polymer. Additionally, the lowest contact angle hystereses were less than 10°, which is one of the requirements of superhydrophobicity and indicates good mobility of the water droplet on the surface, thanks to the Cassie-Baxter state exhibited. Since the electrospun PVDF-co-HFP nanofibre membranes fabricated had a good porosity and oleophilic nature, their potential as the porous part of the SLIPS has been explored. The designed structure exhibited exceptional icephobic properties (lower than 1 kPa, one of the lowest ice adhesion strengths reported in the literature) with smooth surface topography and decreased water contact angle. As the water droplet sat completely on a thin film of lubricating liquid thanks to encapsulated regime achieved, ice adhesion strength was reduced significantly. It was also found that these SLIPS had outstanding flexibility and transparency (>90%), resulting from refractive index matching of polymer used and lubricants. Moreover, a novel multifunctional electrospun membrane was designed and produced for outdoor EMI shielding applications, using recycled polyethylene terephthalate (r-PET) instead of virgin polymers to widen the horizon of using recycled materials. A two-step production process has been applied, which consisted of (i) fabrication of r-PET/magnetite electrospun membranes and (ii) surface modification by fluorinated silane functionalized SiO2 nanoparticles (FSFS). The coaxial waveguide method, a common method to investigate EMI shielding efficiency, was used to investigate EMI shielding properties, and it was found that 20 wt.% magnetite-loaded nanofibre membrane had an EMI shielding efficiency of 22 dB, which was equivalent to above 99% shielding efficiency between 400 MHz and 6 GHz. After FSFS treatment, the nanofibre membrane exhibited Cassie-Baxter state resulted in less than 5° of contact angle hysteresis and approximately 50 kPa ice adhesion strength, thanks to lower surface energy and hierarchical topography, which was beneficial for both icephobic and superhydrophobic performance

Development of electrospun multifunctional fibrous structures for icephobic and superhydrophobic applications

Icephobicity is defined as the ability of a solid surface to prevent ice accumulation or the potential of repelling ice from the surface. On the other hand, superhydrophobicity is a physical property of a surface, which means lacking affinity for water, and tending to repel water. Although these two surface properties have critical application areas such as energy harvesting systems, transportation, corrosion resistance coatings and friction reduction, fabricating superhydrophobic and icephobic surfaces is still a big challenge due to the lack of scalable, straightforward, and cost-effective production methods. Moreover, integrating additional functions, including electromagnetic interference (EMI) shielding and electrical conductivity to these materials to achieve multifunctionality, enables many modern applications, such as EMI shielding protective devices and power transmission systems. Electrospinning is one of the most commonly used methods to produce nano-sized polymeric fibrous membranes or coatings. Unique properties such as high surface-to-volume ratio, high porosity interconnected open pore structures, and adjustable pore sizes make electrospun membranes irreplaceable. However, the potential of using the electrospinning method to produce superhydrophobic and icephobic surfaces is still not investigated in depth. Although there are some studies on the superhydrophobic application of electrospun membranes, considerable challenges remain, such as expensive chemicals, low reproducibility, complex production techniques, and the necessity of a post-treatment or functionalization step. Moreover, electrospun membranes may be a good candidate for icephobic applications based on the Cassie-Baxter icing state or specific material design such as slippery liquid-infused porous structures (SLIPS). In the Cassie-Baxter icing state, water does not penetrate the details of roughness but sits on the air pockets, which provides a low icing area between the ice and the surface, resulting in a lowered work of adhesion of ice. However, no report has been found that explores the potential of the electrospinning method for icephobic applications. In this thesis, the potential of using electrospinning method to fabricate superhydrophobic and icephobic surfaces has been explored. Polyvinylidene fluoride-co-hexafluoropropylene (PVDF-co-HFP), which is a low surface energy polymer, was used to explore the potential of using electrospinning method to design a one-step production method of superhydrophobic surfaces without a post-treatment or nanofiller by only changing the production parameters of electrospinning. The proposed method has significant benefits such as shortened processes, less material use, and low-cost production compared to multistep methods reported in the literature. Moreover, the roles of each parameter on surface topography, contact angle, and fibre formation have been discussed. Superhydrophobicity has been achieved thanks to the synergetic effect of the roughness and the low surface tension of the polymer. Additionally, the lowest contact angle hystereses were less than 10°, which is one of the requirements of superhydrophobicity and indicates good mobility of the water droplet on the surface, thanks to the Cassie-Baxter state exhibited. Since the electrospun PVDF-co-HFP nanofibre membranes fabricated had a good porosity and oleophilic nature, their potential as the porous part of the SLIPS has been explored. The designed structure exhibited exceptional icephobic properties (lower than 1 kPa, one of the lowest ice adhesion strengths reported in the literature) with smooth surface topography and decreased water contact angle. As the water droplet sat completely on a thin film of lubricating liquid thanks to encapsulated regime achieved, ice adhesion strength was reduced significantly. It was also found that these SLIPS had outstanding flexibility and transparency (>90%), resulting from refractive index matching of polymer used and lubricants. Moreover, a novel multifunctional electrospun membrane was designed and produced for outdoor EMI shielding applications, using recycled polyethylene terephthalate (r-PET) instead of virgin polymers to widen the horizon of using recycled materials. A two-step production process has been applied, which consisted of (i) fabrication of r-PET/magnetite electrospun membranes and (ii) surface modification by fluorinated silane functionalized SiO2 nanoparticles (FSFS). The coaxial waveguide method, a common method to investigate EMI shielding efficiency, was used to investigate EMI shielding properties, and it was found that 20 wt.% magnetite-loaded nanofibre membrane had an EMI shielding efficiency of 22 dB, which was equivalent to above 99% shielding efficiency between 400 MHz and 6 GHz. After FSFS treatment, the nanofibre membrane exhibited Cassie-Baxter state resulted in less than 5° of contact angle hysteresis and approximately 50 kPa ice adhesion strength, thanks to lower surface energy and hierarchical topography, which was beneficial for both icephobic and superhydrophobic performance

Structure evolution of phase-separated EC/HPC films for controlled drug release

Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport out of pharmaceutical pellets. The drug transport rate is determined by the structure of the porous films that are formed as the water-soluble HPC leaches out. In industry, the pellets are being coated using a fluidized bed spraying device, and layered films with varying porosity and structure are obtained. A detailed understanding of the formation mechanisms of the multilayered phase-separated structure during production is lacking. Here, we have investigated EC/HPC films produced by spin-coating, which mimics the industrial manufacturing process in a reproducible and well-controlled manner. This work is aimed to understand\ua0 why the\ua0 film structure is layered, and why it exhibits different\ua0 porosities and structures by understanding the film formation mechanisms. The 2D and 3D structures of the EC/HPC films were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), focused ion beam SEM (FIB-SEM) and image analysis. The thickness of the films was measured by profilometry.To be able to understand the multilayer formation, we first studied the structure evolution in EC/HPC monolayer films. The effect of the EC/HPC ratio (from 15 to 85 wt% HPC) on the in-plane and cross-sectional structure evolution was determined. Bicontinuous structures were found for 30 to 40 wt% HPC and discontinuous structures were found for the fractions 15 to 22 and 45 to 85 wt% HPC. The growth of the characteristic length scale followed a power law, , with \ua0for bicontinuous structures, and \ua0 \ua00.45 - 0.75 for discontinuous structures. An image analysis method to characterize the time-dependent 2D curvature evolution was developed. Two main coarsening mechanisms could be identified: interfacial tension-driven hydrodynamic growth for bicontinuous structures and diffusion-driven coalescence for discontinuous structures. The cross-sectional structure evolution shows that during shrinkage of the film, the phase-separated structure undergoes a transition from 3D to nearly 2D structure evolution along the surface. The shrinkage rate was found to be independent of the EC/HPC ratio. A new method to estimate part of the binodal curve in the ternary phase diagram for EC/HPC in ethanol has been developed. For multilayer films, the results showed that the inherent behaviour of the monolayer films have a strong impact on the formation of each new layer in multilayer films. A gradient in structure size with larger structures close to the substrate and smaller structures close to the air surface was found and explained by the redissolution of the layers already deposited during previous deposition cycles. By varying the EC/HPC ratio during the multilayer film production, we showed in situ that the layers do not mix. By varying the spin speed every other layer, we produced a layered film exhibiting varying porosity, proposing a possible explanation for obtaining a layered coating in the industrial process. The findings of this work provide a good understanding of the mechanisms responsible for the morphology development and enable tailoring of multilayer EC/HPC films structure for controlled drug release

New Trends in 3D Printing

A quarter century period of the 3D printing technology development affords ground for speaking about new realities or the formation of a new technological system of digital manufacture and partnership. The up-to-date 3D printing is at the top of its own overrated expectations. So the development of scalable, high-speed methods of the material 3D printing aimed to increase the productivity and operating volume of the 3D printing machines requires new original decisions. It is necessary to study the 3D printing applicability for manufacturing of the materials with multilevel hierarchical functionality on nano-, micro- and meso-scales that can find applications for medical, aerospace and/or automotive industries. Some of the above-mentioned problems and new trends are considered in this book