Development of scaffolds by thermally-induced phase separation from biodegradable poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(butylene succinate)

Aplicat embargament des de la data de defensa fins el 31 de juliol de 2022TIPS process followed by freeze-dtying was used to prepare blodegradable and biocompatible matrices from poly(3- hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) containing 5 and 12 wt% of 3-hydroxyvalerate (HV) and poly(butylene succinate) (PBS). 1,4 dioxane (DXN) and tetrahydofuran (THF) were used as solvents. The cloud points of the polymer solutions were determíned by turbidimetry method, to predict the locus of binodal curve in the binary phase diagrams. A multidirectional cooling from ~70ºC to 25ºC, and then to -5 ºC or -25 ºC was applied to PHBV solutions in the TIPS process. The effect of the applied thermal gradients and HV molar ratio of PHBV copolymer on phase separation mechanism, morphology and mechanical properties of the scaffolds was studied. Upon high HV contents and fast cooling, the solid-liquid phase separation through crystallization of DXN was the controlling mechanism and generated large pores with well-distinguished walls and great structural continuity. The morphologies ascribed to polymer crystallizatíon, mostly with low structural consistency were further discernible upon slow cooling. An improvement in scaffolds rigidity were observed in low HV and fast cooling conditions, due to the increased polymer crystallinity and the greater structural consistency, respectively. PHBV scaffolds showed a complete biocompatibility towards MDCK and NRK cell adhesion and proliferation. A multidirectional cooling from ~70 ºC to -20 or -74 ºC were applied to PBS-DXN and PBS-THF solutions and a uniaxial cooling from ~70ºC to -74 or -196 ºC to PBS-DXN. 5 and 100 wt% ofcurcumin (CUR) and piperine (PIP) natural drugs were loaded into PBS matrices via a one-step TIPS fabrication/drug loadlng protocot. Utílizing DXN and THF solvents, solid-liquid and liquid-liquid phase separation were respectívely detected as the main mechanisms responsible for creating the porous structures, while the subregions composed of crysta llized PBS were also obse rved . The applied uniaxial thermal gradient enabled DXN solvent to crystallize along the heat transfer direction and form an oriented pare structure. Although the low drug values did not significantly influence the morphology, the high-level drug loading gave rise to the decreased porosity and superficial roughness ofthe scaffolds . A uniform distribution ofprismatic PIP crystals and matrix-integrated CUR aggregation was observed all overthe structure. The integration of CUR which was confirmed by the physicochemical analyses attributed to a possible interaction with the PBS matrix, as it also showed a slower release profile compared to PIP. Oriented matrices showed greater biocompatibility and also retarded drug release from their·dense spherulitic pore walls. Biobased highly rigid polycarbonate and polyesters with terpene oxide units were blended with PBS at different ratios to increase the biocontents and modify the properties. Ali the terpene-derived polymers exhibi ted high Tg, thermal stability biocompatibility and mechanical strength. Their rigid nature and stiff chains led to insignificant hydrolytic and enzymatic biodegradation, while an accelerated degradation in oxidative media was observed. Their blends with PBS were also biocom patible and to sorne extent biodegradable . 30 wt% of poly (PA-LO) the copolyester derived from phthalic anhydride and limonene oxide, was blended with PBS and porous matrices were prepared by a one-step TIPS fabrication/blending protocol. Multidirectional cooling to -20 ºC or-74 ºC and uniaxial cooling to -74 ºC or-196 ºC was applied to PBS-Poly (PA-LO)-DX N system. Although the blending did not affect the morphology and pore structure of the random/oriented matrices, could somewhat restrict the crystallization of PBS from the solution during the TIPS process. Accordin gly, thinner polymer leaves upon multídirectional and lower thermal gradient, and smaller, less planar and less integrated spherulites were formed upon high uniaxial gradient.El proceso TIPS seguido de liofilización fue usado para preparar matrices porosas ("scaffolds") biodegradables y biocompatibles a partir del poliéster poli (3-hidroxibutirato-co-3-hidroxivalerato) (PHBV) que contiene 5 y 12 wto/o de 3- hidroxivalerato (HV) y del poliéster poli(butilensuccinato) (PBS). El 1.4 dioxano (DXN) yel tetrahidofurano (THF) fueron los disolventes. En el TIPS para las disoluciones de PHBV se aplicó un enfriamiento multidireccional de 70 a 25ºC y luego a -5 ó -25ºC. Se estudiaron los efectos del gradiente térmico y contenido de HV del copolímero sobre el mecanismo de separación de fases, la morfología y propiedades mecánicas de los scaffolds. La separación de fase sólido-líquido en la cristalización del DXN durante el enfriamiento rápido fue el mecanismo que controla la formación de los scaffolds del copolímero con alto contenido de HV. Los scaffolds mostraron grandes poros con paredes bien formadas y gran integridad estructural. Las morfologías atribuidas a la cristalización del polímero. en su mayoría con poca integridad estructural. fueron obtenidas con el enfriamiento lento. Se observó una mejora en la rigidez y mayor integridad estructural de los scaffolds con bajo HV y enfriamiento rápido. debido al aumento de la cristalinidad del polímero. Los scaffolds de PHBV mostraron gran biocompatibilidad determinada por la adhesión y proliferación de células MDCK y NRK. Las disoluciones de PBS-DXN y PBS-THF fueron enfriadas multidireccionalmente de 70ºC a -20 ó -74ºC. y de manera uniaxial para PBS-DXN de 70ºC a -74 ó -196ºC. Los scaffolds de PBS durante su preparación por TIPS fueron cargados con 5 y 100 wt% de curcumina (CUR) o piperina (PIP). La separación de fases sólido-líquido y líquido-líquido (con los disolventes DXN y THF respectivamente) fueron los principales mecanismos responsables para formar las estructuras porosas y subregiones compuestas por PBS cristalizada. El gradiente térmico uniaxial permitió la cristalización del DXN a lo largo de la dirección de transferencia de calor y la formación de poros orientados. La presencia de los fármacos no influyo significativamente en la morfología de los scaffolds. La gran cantidad del fármaco disminuye la porosidad y la rugosidad superficial en los scaffolds. En los scaffolds se observó una distribución uniforme de cristales de PIP y agregación de CUR. La integración de CUR indico una posible interacción con la matriz de PBS y mostró un perfil de liberación más lento en comparación con PIP. Los scaffolds orientados mostraron una mayor biocompatibilidad y una liberación lenta del fármaco debido a sus densas paredes formadas por esferulitas policarbonatos y poliésteres biobasados altamente rígidos y formados por unidades de óxido de terpeno fueron mezclados con PBS en diferentes proporciones para aumentar su biocontenido y modificar sus propiedades. La Tg. estabilidad térmica, biocompatibilidad y resistencia mecánica son elevadas en los polímeros derivados del terpeno. La biodegradación hidrolítica y enzimática de estos polímeros fue insignificante debido a la rigidez de sus cadenas. mientras una degradación acelerada fue lograda en medios oxidativos. Las mezclas con PBS fueron biocompatibles y algo biodegradables. La mezcla del copoliéster derivado de anhídrido phtalico y óxido de limoneno (poli(PA-LO)) con PBS (30:70 wo/o, respectivamente) fue usada para preparar scaffolds con la metodología TIPS. El enfriamiento multidireccional a -20ºC ó -74ºC y el enfriamiento uniaxial a -74ºC ó -196ºC fue aplicado al sistema PBS-Poly(PA-LO)-DXN. Esta mezcla no influye en la morfología y estructura de los poros de los scaffolds con porosidad orientada o al azar. Durante el proceso TIPS, la cristalización del PBS fue afectada. En consecuencia, el PBS en el menor gradiente térmico multidireccional forma estructuras en hojas más delgadas y con el mayor gradiente uniaxial se formaron esferolitas más pequeñas, menos planas y menos integradas.Postprint (published version

Fundamentals of chemical reaction engineering

This book is an introduction to the quantitative treatment of chemical reaction engineering. The level of the presentation is what we consider appropriate for a one-semester course. The text provides a balanced approach to the understanding of: (1) both homogeneous and heterogeneous reacting systems and (2) both chemical reaction engineering and chemical reactor engineering. We have emulated the teachings of Prof. Michel Boudart in numerous sections of this text. For example, much of Chapters 1 and 4 are modeled after his superb text that is now out of print (Kinetics a/Chemical Processes), but they have been expanded and updated. Each chapter contains numerous worked problems and vignettes. We use the vignettes to provide the reader with discussions on real, commercial processes and/or uses of the molecules and/or analyses described in the text. Thus, the vignettes relate the material presented to what happens in the world around us so that the reader gains appreciation for how chemical reaction engineering and its principles affect everyday life. Many problems in this text require numerical solution. The reader should seek appropriate software for proper solution of these problems. Since this software is abundant and continually improving, the reader should be able to easily find the necessary software. This exercise is useful for students since they will need to do this upon leaving their academic institutions. Completion of the entire text will give the reader a good introduction to the fundamentals of chemical reaction engineering and provide a basis for extensions into other nontraditional uses of these analyses, for example, behavior of biological systems, processing of electronic materials, and prediction of global atmospheric phenomena. We believe that the emphasis on chemical reaction engineering as opposed to chemical reactor engineering is the appropriate context for training future chemical engineers who will confront issues in diverse sectors of employment. We gratefully acknowledge Prof. Michel Boudart who encouraged us to write this text and who has provided intellectual guidance to both of us. MED also thanks Martha Hepworth for her efforts in converting a pile of handwritten notes into a final product. In addition, Stacey Siporin, John Murphy, and Kyle Bishop are acknowledged for their excellent assistance in compiling the solutions manual. The cover artwork was provided courtesy of Professor Ahmed Zewail's group at Caltech, and we gratefully thank them for their contribution. We acknowledge with appreciation the people who reviewed our project, especially A. Brad Anton of Cornell University, who provided extensive comments on content and accuracy. Finally, we thank and apologize to the many students who suffered through the early drafts as course notes. We dedicate this book to our wives and to our parents for their constant support