Partial Molar and Specific Volumes of Polyelectrolytes: Comparison of Experimental and Predicted Values in Salt-free Solutions

The partial molar volume, .hivin.V, and the partial sp. vol., .hivin.n, were estd. for more than 25 polyelectrolyte structures. The materials investigated by d. measurements in highly dild. aq. solns. (c < 10-2 monomol/L) included both synthetic polyelectrolytes and chem. modified natural polymers. Through a detailed anal., related to the chem. structure and macromol. parameters, a linear dependence between the copolymer compn. and the partial vols. could be identified for diallyldimethylammonium chloride/acrylamide copolymers. Additivity could also be shown for sodium cellulose sulfate having various degrees of substitution. For a homologous series of poly(vinylbenzyltrialkylammonium chloride)s, a linear correlation between the molar mass of the monomer unit and the partial molar volume was obtained. No influence of the d.p. was obsd. as long as the contour length exceeds the Debye length. The exptl. results were used to evaluate the general applicability of the additivity schemes of Durchschlag and Zipper, as well as Gianni and Lepori, to polyelectrolytes. Agreement between exptl. and calcd. partial vols. strongly depends on the chem. structures. In the case of the synthetic polycations, the deviations are in a similar range for both models though somewhat smaller for the Gianni/Lepori model. The use of the Durchschlag/Zipper model yields much better agreement for the anionic biopolymers with deviations generally less than 3%. The tendency of the empirical models is correct; however, the precision may be improved by regressing of parameters from the exptl. results. The new exptl. data may also be useful in polyelectrolyte characterization. [on SciFinder (R)]

Development of functionalized alginate-based hydrogels to reduce fibrosis in the transplantation of microencapsulated cells

François Rémi Pierre Noverraz

Nowadays, the development of cell therapy relies mainly on the advances made toward cell microencapsulation which allows to evade the need for immunosuppression during cell transplantation. Among the materials considered for cell encapsulation, hydrogels distinguish themselves by their exceptional properties. Due to its gelling properties in contact with divalent cations, the biopolymer sodium alginate (Na-alg), has been widely studied for the microencapsulation and transplantation of cells. However, several defects notably in permselectivity and durability in vivo is limiting the translation of alginate-based hydrogels in clinical applications. In addition, the transplantation of cells without immunosuppressive treatment have to face adverse host responses such as inflammation and fibrosis. At the moment, several approaches have been considered for the development of an ideal material for cell encapsulation; however many challenges still remain in this domain. Hence, this research project focused on the development of hydrogels in order to improve their properties toward cell encapsulation. The first part of this research focused on the development of new types of one-component hybrid alginate-based hydrogels. These hydrogels combine the gelling properties of Na-alg with covalent crosslinking within the same polymeric structure. In order to do so, a new synthetic approach was developed allowing the functionalization on the hydroxyl position of alginate with heterobifunctional poly(ethylene glycol) (PEG) linkers through carbamate bond. This allowed to maintain the carboxyl moieties available for the formation of electrostatic interactions. Two types of one-component hybrid hydrogel were developed with this method adding either thiols or lipoyl moieties on alginate leading to an improvement of mechanical properties while preserving a good biocompatibility. Yet, transplantation of encapsulated cells in a foreign host body have to face immune response, in particular inflammation and pericapsular fibrosis overgrowth (PFO) which ultimately leads to necrosis of the encapsulated cells and loss of graft functionality. Therefore, the second part of this research project focused on tuning the composition of the polymeric components of the hydrogels with anti-inflammatory agents which would reduce PFO in vivo. Different anti-inflammatory agents were considered for this purpose. The best candidate (ketoprofen) was then PEGylated via either ester or amide bond and grafted on the backbone of alginate to ensure a controlled release at the site of transplantation. By analyzing the fibrotic tissue around the microspheres, it was observed that the incorporation of ketopreofen on the structure of the hydrogel significantly reduced PFO 30 days after transplantation. In summary, Na-alg was functionalized with a new synthetic methodology allowing the incorporation of either functionalities reinforcing the mechanical resistance of the hydrogel or anti-inflammatory compounds improving the biocompatibility of the graft.

EPFL2018

Extraction and controlled functionalization of lignin for materials applications

Stefania Bertella

Lignin is a renewable aromatic polymer that due to its abundance and unique chemical structure is a promising candidate to replace aromatic materials that are currently sourced from fossil oil. The same structure of lignin poses however drawbacks for its valorization. The high temperature and strong pH that are generally used to isolate lignin, make this polymer prone to reactions of condensation during its extraction. This translates into isolated lignins where most of their native functional groups are eliminated in favor of the formation of interunit carbon-carbon linkages. The lack of control on lignin's chemical functionalities ultimately hinders the use of this polymer for the development of new materials. Many research groups have been trying to tackle these challenges by developing new processes that could allow for the efficient isolation of lignin without compromising on its functional groups. Amongst these, the Aldehyde-Assisted Fractionation (AAF), which relies on the formation of acetal groups between lignin's ß-O-4 units and an added aldehyde, was proven to be efficient in isolating high yields of lignin, that could be then quantitatively depolymerized into small aromatic monomers. Inspired by this research, the aim of my work is to take advantage of the AAF to quantitatively isolate lignin from lignocellulose, at the same time introducing on the biopolymer scaffold new functional groups that could allow for more effective development of lignin-based materials. My work is based on a Multifunctional-AAF, in which the multifunctional aldehydes can react with the lignin via the formation of acetals, at the same time leaving on the biopolymer additional functionalities. In the first part of my thesis, I show how the extraction and simultaneous functionalization of lignin can be achieved by using terephthalic aldehyde (TALD). In addition to successfully functionalizing the lignin, I demonstrate how the degree of functionalization can be precisely controlled and monitored via 1H NMR, yielding a material with high reactivity towards phenolation. In the second part, I show how the isolation and controlled functionalization of lignin can be translated to the use of other aldehydes, namely glyoxylic acid (GA), to functionalize lignin with carboxylates, quantified via 31P NMR. The isolated lignin offers in this case unique avenues for the development of more sustainable surfactants. In the last chapter of the thesis, I show that the Multifunctional-AAF can be expanded to isolate and functionalize lignin with multiple functionalities by using mixtures of aldehydes (TALD and GA), demonstrating again that each functional group can be easily quantified. These lignins, extracted with different ratios of the two functional groups, showed dissimilar properties in terms of solubility and reactivity towards gelatin. We used these lignins to develop lignin-gelatin based hydrogels, showing how the bi-functionalization was pivotal for the formation of hydrogels with improved rheological, mechanical, self-healing and adhesive properties. In summary, this thesis shows the development of a new approach for lignin extraction and simultaneous valorization. The versatility of this process enables more efficient functionalization, allowing the obtainment of lignins which are "tailor-made" for their end use. The control over lignin's chemical structure and functionalization will pave the way for the use of lignin in high-end application.

EPFL2022

3D Printing and Supercritical Foaming of Hierarchical Cellular Materials

Matteo Gregorio Modesto Marascio

Hierarchical porous structures have been gathering interest in different fields owing to their unique properties associated with their multi-scale features. The observation of natural materials brought new insights into the functionality of cellular materials and inspired new processes to produce synthetic hierarchical structures. Such hierarchical cellular materials have shown significant potential in many applications, as filtering, tissue engineering and drug delivery. Polymers in particular gathered a burgeoning interest thanks to their ease of processing, which allows to produce structures at high strength/density ratio and high surface area with defined porosity. In the present study, it is proposed to develop novel technologies to manufacture polymer cellular structures. From the application of Supercritical Carbon Dioxide Foaming (ScCO2) to Fused Deposition Modelling / Fused Filament Fabrication (FDM / FFF), an extrusion based additive manufacturing technology, hierarchical porous structures were created. The material transformation phenomena and the processing window of this homothetic foaming processed were studied. The fine tuning of the foaming parameters allowed creating a micro cellular porosity with-in a 3D printed structure, without modifying the 3D topology. This allowed producing a wide range of cellular struc-tures with controlled multi scale porosity and stiffness reduced up to hundred times the stiffness of the 3D printed cellular structures. Homothetic foaming was then applied to biopolymers in order to create gradient hierarchical porous structures. In particular, articular cartilage and bone (osteochondral) defects were targeted. Cartilage repair is a challenging clinical problem because large defects do not regenerate. Tissue engineering offers a solution by implanting a material, defined as scaffold, loaded with cells to induce a regeneration in the tissue that otherwise would not occur. Multi material Poly(lactide-co-caprolactone) â Poly(lactide-BTCP) cellular structures were successfully processed into a scaffold able to replicate the complex gradient mechanical properties of the osteochondral tissue. In particular, the processing windows to process multi material 3D printed and foamed structures was established. The mechanical properties under compression of these scaffolds were compared to the values measured by nanoindentation on human articular cartilage, showing a good correlation between scaffold and target application. Furthermore, from the developed knowledge, a novel additive manufacturing method is proposed from the inte-gration of FDM/FFF and ScCO2 into a single process, named 3D Foam Printing. 3D Foam Printing was applied to process structures with hollow filaments or filaments with radial porosity with live porosity control during the process. The influence of processing parameters on foam morphology was investigated. Different cellular structures achievable by tuning the printing temperature and speed were described for different biomaterials. The processes described in this work allowed to mimic the complex mechanical properties of the osteochondral tissue, a natural hierarchical material. However, they demonstrated to be relevant to a wide range of materials, as polymers, blends and composites. This is particularly true for 3D Foam Printing, which could positively influence many engineering applications, as aerospace, medicine and energy, where tuneable cellular polymers are highly demanded.

EPFL2018

Development of functionalized alginate-based hydrogels to reduce fibrosis in the transplantation of microencapsulated cells

François Rémi Pierre Noverraz

EPFL2018

3D Printing and Supercritical Foaming of Hierarchical Cellular Materials

Matteo Gregorio Modesto Marascio

EPFL2018

Extraction and controlled functionalization of lignin for materials applications

Stefania Bertella

EPFL2022