Síntesis y caracterización de copolímeros bloque biocompatibles

La polimerización aniónica es una de las vías sintéticas para obtener macromoléculas con estructuras bien definidas y mínima heterogeneidad. Mediante el correcto empleo de esta técnica es posible obtener homo y copolímeros con un control muy preciso de ciertos parámetros moleculares de importancia, entre los que se destacan la masa molar, la distribución de masas molares, la composición y la funcionalidad del extremo de cadena. Otras vías sintéticas más modernas (que involucran procedimientos experimentales menos complejos que los de la polimerización aniónica clásica) son los métodos de polimerización radicalaria por desactivación reversible (RDRP, por sus siglas en inglés), como por ejemplo la polimerización reversible por adición, fragmentación y transferencia (RAFT).En esta Tesis Doctoral se sintetizaron poli(dimetilsiloxano)s telequélicos (ω-PDMS y α,ω-PDMS) mediante polimerización aniónica clásica en alto vacío, empleando una ruta sintética original. El procedimiento permitió obtener ω-PDMS y α,ω-PDMS con grupos funcionales específicos. En particular, se empleó un PDMS-hidroxil terminado para sintetizar copolímeros bloque con -caprolactona (SCL#), de estructura y composición definida. Por otro lado, se sintetizaron copolímeros en base ε-caprolactona/2-hidroxietil metacrilato (HEMACL#) empleando el método de polimerización RAFT. De esta forma, se obtuvieron diversos copolímeros bloque y ramificados a partir de monómeros de naturaleza biocompatible.Los copolímeros obtenidos se caracterizaron fisicoquímicamente empleando diversas técnicas analíticas, y se determinó que los procedimientos experimentales propuestos permitieron obtener materiales con excelente control de sus parámetros moleculares y composición. También se estudió su comportamiento térmico según el modelo de Avrami para determinar parámetros cinéticos de interés, tales como la tasa de cristalización, los tiempos medios y la geometría espacial del proceso de cristalización, en rangos de temperaturas comprendidos entre 16 - 24 °C y 40 - 48 °C. Se determinó que la arquitectura molecular influye notablemente en el comportamiento térmico de los HEMACL# y que el bloque de PDMS en los SCL# les confiere estabilidad térmica a altas temperaturas. Con estos últimos copolímeros se obtuvieron recubrimientos bioactivos con un biovidrio (BG) empleando la técnica de deposición electroforética (EPD). Los recubrimientos obtenidos mostraron adecuada adherencia al sustrato metálico y tasas de deposición más altas comparadas con otros materiales de uso común como los poliésteres.Los resultados informados en esta Tesis constituyen un aporte de interés respecto a la síntesis y caracterización de copolímeros en base siloxano y ε-caprolactona con estructura y composición definida. En tal sentido, los copolímeros sintetizados permiten inferir su potencial uso en aplicaciones específicas tales como materiales de impresión 3D, obtención de nanofibras por electrohilado o preparación de soportes biocompatibles para promover crecimiento celular.Macromolecules with well-defined structures and minimal heterogeneity can be synthesized by anionic polymerization. By employing this technique, it is possible to obtain homo and copolymers with a precise control of certain molecular parameters, such as molar masses distribution, composition and chain-end functionality. Other modern synthetic routes (which involve experimental procedures simpler than classical anionic polymerization) are reversible deactivation radical polymerizations (RDRP), such as the reversible polymerization by addition, fragmentation and transfer (RAFT). In this work, telechelic poly(dimethylsiloxane)s (ω-PDMS and α,ω-PDMS) were synthesised by classical anionic polymerization (high-vacuum techniques), by using an original synthetic approach to afford a bifunctional anionic initiator (BI). By employing conventional lithium alkyls and the synthesised BI, ω-PDMS and α,ω-PDMS with specific functional groups were obtained. In particular, hydroxyl-terminated PDMS were employed as macroinitiator to synthesise block copolymers based on ε-caprolactone (SCL#) with macromolecular homogeneity in a broad range of compositions. On the other hand, block/graft copolymers (HEMACL#) from ε-caprolactone and 2-hydroxyethyl methacrylate monomers were synthesised by combining ring-opening (ROP) and RAFT polymerization in a one-pot procedure. Copolymers obtained were physicochemically characterized by using conventional analytical techniques. According to the results obtained, an excellent control of the molecular parameters and composition was observed. In addition, the thermal behavior of SCL# and HEMACL# copolymer was also studied according to Avrami’s model. From this analysis, kinetic parameters such as crystallization rate, half-times of crystallization and spatial geometry of crystallization process were determined for two crystallization temperature ranges, 16 - 24 ºC and 40 - 48°C. The molecular architecture influences the thermal behavior vi of HEMACL# copolymers and the presence of PDMS block provide thermal stability at high temperatures to SCL# copolymers. Particularly, from these last copolymers, bioactive coatings with bioglass (BG) were obtained by employing electrophoretic deposition technique (EPD). Coatings showed a good adherence to the metallic substrate and high deposition rates when compared to commonly used materials such as polyesters. Results reported in this work provide useful information regarding the synthesis and characterization of well-defined copolymers based on siloxane and ε-caprolactone. In this sense, a potential use of copolymers in specific applications, such as 3D printing materials, nanofibers from electrospinning or biocompatible supports to promote cell growth can be inferred.Fil: Redondo, Franco Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Aplicadas a la Industria; Argentin

Análise comparativa entre ácido polilático e polietileno verde através de patentes

A indústria dos polímeros sintéticos, que garantem durabilidade e versatilidade de aplicações ao consumidor, tem seu cenário modificado quando se deparam com diversas dificuldades como o preço elevado do petróleo, conflitos geopolíticos e a crescente preocupação da população com o ambiente. Fica então evidente a necessidade do desenvolvimento de novos materiais plásticos, os biopolímeros, que podem substituir os sintéticos convencionais e minimizar impactos ambientais. Este recente mercado motivou o presente estudo tecnológico e possibilitou a visualização do setor de Pesquisa e Desenvolvimento (P&D) dessa área no Brasil e no mundo. Após a identificação de dois polímeros promissores, Ácido Polilático (PLA) e Polietileno Verde (PE), foi aplicada uma metodologia para análise da tecnologia protegida por empresas voltadas para esses dois polímeros. A busca de patentes teve como as bases INPI, para análise nacional e o Derwent, para mundial, o que permitiu tratar os dados e avaliar a evolução do setor em termos de P&D e tecnologia. Por fim, constatou-se que as empresas Toray e Teijin são as maiores detentoras de patentes para o PLA, já para o PE, tem-se a Arkema e a Toray no banco de dados mundial e a Dow Global no banco de dados nacional. Com as análises dos resultados obtidos pode-se obter uma visão geral da atual posição da indústria brasileira e a inserção desses dois polímeros no mercado nacional, além disso, identificando qual o grau de amadurecimento desses produtos para competir com os termoplásticos tradicionais

Bicontinuous Materials from Telechelic Macromonomers Using Thiol-ene Chemistry

Bicontinuous structures are beneficial to many applications from health and medicine to energy and the environment. Although these materials can be used for many applications, current strategies yield bicontinuous structures only under highly specific processing conditions. Development of a versatile platform to reliably obtain bicontinuous morphologies will be broadly beneficial. This work presents two platforms that can be used to produce bicontinuous morphologies using a simple Mitsunobu/thiol-ene strategy. This platform allows for the incorporation of a variety of polymer chemistries to yield well-defined polymer networks or multiblock copolymers (MBCs). It also allows for the systematic investigation of factors affecting the morphology such as the molecular weight between cross-links and the volume fraction of the network components. The ease at which these variables can be systematically investigated allows for rigorous fundamental studies of these composite systems. In the first co-network system, the platform’s ability to tailor mechanical properties while maintaining good ion conductivity was demonstrated by comparing PEG-PDMS co-networks to PEG networks using EIS and DMA. Also, the effect of salt loading on thermal properties was explored using DSC. The second system, PEG-PS co-networks, demonstrated that varying the molecular weight of the precursor polymers results in control over d-spacing that fits well to de Gennes’s prediction (d ~ Mn0.5). Despite the variation in d-spacing, 22 - 55 nm, the ion conductivity and mechanical properties remained relatively consistent, demonstrating versatility in this system. Critical percolation thresholds were investigated by using ion conductivity and storage modulus to probe the continuity of the PEG and PS phases, respectively. Percolation theory suggests this system has a wide bicontinuous compositional window from fPEG = 0.225 -0.675. A preliminary phase diagram was generated by combining results from the molecular weight and volume fraction series. Finally, a simple synthesis for (MBCs) is demonstrated using the same Mitsunobu/thiol-ene platform. MBCs with ~4 blocks and two or three types of macromonomers were synthesized. Disordered phase separation was shown by SAXS and AFM. The versatile Mitsunobu/thiol-ene platform is easily able to synthesize different architectures using a range of polymer chemistries for various morphology and property studies

Toward Enhancing the Synthesis of Renewable Polymers: Feedstock Conversions and Functionalizable Copolymers

This thesis describes research under the rubric of the Center for Sustainable Polymers that is aimed at two separate goals. The goal of the first project (Chapters 1 and 2) was to develop a deeper mechanistic understanding of a method for the synthesis of linear α-olefins, while the second aimed at synthesizing statistical copolymers that incorporate olefin-containing monomers through ring-opening transesterification polymerization and showing that these copolymers could be functionalized. In Chapter 1, published methods for the conversion of fatty acids to linear α-olefins are reviewed to provide context for the mechanistic work we accomplished (Chapter 2). In Chapter 2 the dehydrative decarbonylation mechanism is investigated with the hopes of identifying factors that may lead to better catalyst design. A series of Pd-acyl complexes were synthesized with hydrocinnamoyl chloride and phosphine ligands. The three different ligands (PtBu3, PPh3, and dppe) were chosen for their ability to induce differing coordination environments around Pd to examine what role the steric environment has specifically on the decarbonylation and β-hydride elimination steps. Experimental work was informed by theory to better understand the various thermodynamic differences between ligands and upon chloride abstraction from Pd. A reactivity trend, as determined by the formation of styrene, was observed in the order of PtBu3 \u3e dppe \u3e PPh3. Key findings include: the β-hydride elimination step has the highest impact from ligand choice, the low coordination number induced by PtBu3 lowers reaction barriers for all steps of the catalytic cycle and the trans coordination of the Pd complex with two PPh3 ligands contributes to a low efficiency for styrene production. In Chapter 3, a series of olefin-containing caprolactone monomers were statistically copolymerized with racemic-lactide to create a new class of copolymers. The new copolymers, bearing uniformly distributed pendant olefins, underwent a series of post-polymerization modification reactions to convert the alkenes into numerous functionalities such as hydroxyl, bromo and epoxide units. Furthermore, small, and large molecules, such as 1-octanethiol, polyethylene glycol, polycaprolactone, polydimethylsiloxane and polymethacrylate were fused with the copolymers through grafting-to and grafting-from reactions by thiol-ene, metathesis, ring-opening polymerization and free radical polymerization reactions

VAD in failing Fontan: simulation of ventricular, cavo-pulmonary and biventricular assistance in systolic/diastolic ventricular dysfunction and in pulmonary vascular resistance increase.

Aim: Due to the lack of donors, VADs could be an alternative to heart transplantation for Failing Fontan patients (PTs). Considering the complex physiopathology and the type of VAD connection, a numerical model (NM) could be useful to support clinical decisions. The aim of this work is to test a NM simulating the VADs effects on failing Fontan for systolic dysfunction (SD), diastolic dysfunction (DD) and pulmonary vascular resistance increase (PRI). Methods: Data of 10 Fontan PTs were used to simulate the PTs baseline using a dedicated NM. Then, for each PTs a SD, a DD and a PRI were simulated. Finally, for each PT and for each pathology, the VADs implantation was simulated. Results: NM can well reproduce PTs baseline. In the case of SD, LVAD increases the cardiac output (CO) (35%) and the arterial systemic pressure (ASP) (25%). With cavo-pulmonary assistance (RVAD) a decrease of inferior vena cava pressure (IVCP) (39%) was observed with 34% increase of CO. With the BIVAD an increase of ASP (29%) and CO (37%) was observed. In the case of DD, the LVAD increases CO (42%), the RVAD decreases the IVCP. In the case of PRI, the highest CO (50%) and ASP (28%) increase is obtained with an RVAD together with the highest decrease of IVCP (53%). Conclusions: The use of NM could be helpful in this innovative field to evaluate the VADs implantation effects on specific PT to support PT and VAD selection

Lipase-Mediated Enzymatic Catalysis For The Synthesis of New Chiral Polymers

Immobilized lipase B from Candida antarctica (N435) was investigated as a potential biocatalyst to generate silicone-based chiral polymers from monomers derived from the enzymatic dihydroxylation of bromobenzene. Several conditions and parameters have been investigated for this purpose and lipase transesterification preference to each of the free secondary alcohols in the chiral monomers was documented. The N435 was challenged with a series of substrates where the free alcohol moieties were systematically protected in order to study the substrate preference(s) for the transesterification reactions

Chapter 34 - Biocompatibility of nanocellulose: Emerging biomedical applications

Nanocellulose already proved to be a highly relevant material for biomedical applications, ensued by its outstanding mechanical properties and, more importantly, its biocompatibility. Nevertheless, despite their previous intensive research, a notable number of emerging applications are still being developed. Interestingly, this drive is not solely based on the nanocellulose features, but also heavily dependent on sustainability. The three core nanocelluloses encompass cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial nanocellulose (BNC). All these different types of nanocellulose display highly interesting biomedical properties per se, after modification and when used in composite formulations. Novel applications that use nanocellulose includewell-known areas, namely, wound dressings, implants, indwelling medical devices, scaffolds, and novel printed scaffolds. Their cytotoxicity and biocompatibility using recent methodologies are thoroughly analyzed to reinforce their near future applicability. By analyzing the pristine core nanocellulose, none display cytotoxicity. However, CNF has the highest potential to fail long-term biocompatibility since it tends to trigger inflammation. On the other hand, neverdried BNC displays a remarkable biocompatibility. Despite this, all nanocelluloses clearly represent a flag bearer of future superior biomaterials, being elite materials in the urgent replacement of our petrochemical dependence

Polymeric Carriers for Biomedical and Nanomedicine Application

This book focuses on the design of polymeric delivery systems for biomedical and nanomedicine applications as well as on understanding how such biomaterials interact in the physiological environment. The reader will find an encompassing view on the state-of-the-art of polymeric carriers, showing how current research deals with new stimuli-responsive systems for cancer therapies and biomedical challenges, namely overcoming the skin barrier. The published papers cover topics ranging from novel production methods and insights on hybrid polymers to applications as diverse as nanoparticles, hydrogels and microneedles for antifungal skin therapy, peptide and siRNA delivery, enhanced skin absorption of bioactive molecules, and anticancer therapy. The book comprises one review paper and nine research papers