Conductos de ácido hialurónico para el crecimiento axonal guiado

[EN] Since a considerable number of factors limit or prevent the autonomous regeneration of injured or degenerated tracts in the nervous system, its effective restoration is a rare phenomenon. Therefore, conventional medicine has only succeeded in therapies aimed at treating the symptoms and effects of the damage. In order to revert them and to restore the functionality of a neuronal network, tissue engineering is currently researching about the synergic use of cells, bioactive molecules and three-dimensional biocompatible supports. More precisely, the regeneration of nervous system damaged structures is being studied through strategies like the so-called neural conduits. In this thesis, a channeled porous scaffold based on hyaluronic acid, a hydrophilic natural polymer, has been designed, developed and characterized, both physicochemically and biologically. By chemically crosslinking this polymer through divinyl sulfone and next lyophilizing it, a degradable and millimeter-size conduit has been obtained, soft but stable in physiological medium. The conduit wall has a singular three-layer distribution, able to avoid glial cells migration through it, but entirely permeable to nutrients and proteins. Furthermore, if Schwann cells are cultured for 10 days within the conduit's lumen, they create a cell tube-like structure with several hundreds of microns in diameter, thin but dense, similar to those of nerve fascicles. The ability of the conduits, the Schwann cells macrosheath and a bundle of 30 um poly-L-lactic acid fibers to guide the growth of neurons in dorsal root ganglia explants has been evaluated as well. Only the biohybrid system, composed by the conduit, the stretched fibers within and the cells macrosheath, is a beneficial enough context to permit neurons grow at a similar rate to other promising strategies in tissue engineering of the nervous system.[ES] La regeneración de tractos dañados o degenerados del sistema nervioso de manera autónoma es un fenómeno infrecuente, ya que están implicados una considerable cantidad de factores que la limitan u obstaculizan. Por ello, la medicina convencional tan solo ha logrado limitados éxitos a este respecto, tratando únicamente los síntomas y los efectos del daño. Para intentar revertirlo y lograr la reconexión funcional de neuronas, en la actualidad la ingeniería tisular está investigando acerca de la aplicación sinérgica de células, moléculas bioactivas y soportes tridimensionales biocompatibles. Concretamente, para regenerar estructuras del sistema nervioso se trabaja en la estrategia conocida como conductos neurales. En esta tesis se ha diseñado, desarrollado y caracterizado tanto fisicoquímica como biológicamente un andamiaje acanalado poroso basado en ácido hialurónico, un polímero hidrófilo natural. Mediante el entrecruzamiento químico de este mediante divinil sulfona y su posterior liofilización, se ha logrado obtener un conducto milimétrico degradable, blando pero estable en medio fisiológico que, además, posee una pared con una singular distribución en tres capas capaz de evitar la migración de células de glía a su través, pero totalmente permeable a nutrientes y proteínas. Asimismo, las células de Schwann cultivadas en el interior del conducto proliferan confinadamente hasta formar al cabo de 10 días una estructura celular tubular de varios cientos de micras de diámetro, delgada pero densa, similar a las estructuras fasciculares de los nervios. Se ha evaluado, además, la capacidad tanto de los conductos acanalados como de la macrovaina de células de Schwann y de un haz de fibras de ácido poli-L-láctico de unos 30 um de diámetro para guiar el crecimiento de neuronas de explantes de ganglios de la raíz dorsal in vitro. Tan solo el sistema biohíbrido formado por el conjunto del conducto, las fibras estiradas en su interior y la vaina de células es capaz de aportar un contexto amigable tal para permitir a las neuronas crecer a tasas del mismo orden que en otras estrategias prometedoras en ingeniería tisular del sistema nervioso.[CA] La regeneració autònoma de tractes del sistema nerviós danyats o degenerats és un fenomen infreqüent, en tant que hi son implicats una considerable quantitat de factors que la limiten o obstaculitzen. Per aquesta causa, la medicina convencional tan sols ha assolit èxits limitats a aquest respecte, tractant únicament els símptomes i els efectes del dany. Per tractar de revertir-ho i aconseguir la reconnexió funcional de neurones, en l'actualitat l'enginyeria tissular està investigant sobre l'aplicació sinèrgica de cèl·lules, molècules bioactives i suports tridimensionals biocompatibles. Més concretament, per a regenerar estructures del sistema nerviós es treballa amb l'estratègia coneguda com conductes neurals. A aquesta tesi s'ha dissenyat, desenvolupat i caracteritzat, tant fisicoquímica com biològicament, una bastida acanalada porosa basada en àcid hialurònic, un polímer hidròfil natural. Mitjançant el seu entrecreuament químic amb divinil sulfona i la seua posterior liofilització, s'ha aconseguit obtenir un conducte mil·limètric degradable, tou però estable en medi fisiològic que, a més a més, posseeix una paret amb una singular distribució en tres capes capaç d'evitar la migració de cèl·lules glials al seu través, però totalment permeable a nutrients i proteïnes. Tanmateix, les cèl·lules de Schwann cultivades en l'interior del conducte proliferen confinades fins que formen, als 10 dies, una estructura cel·lular tubular de centenars de micres de diàmetre, prima però densa, semblant a les estructures fasciculars dels nervis. S'ha avaluat, a més, la capacitat dels conductes acanalats, de la baina de cèl·lules de Schwann i d'un feix de fibres d'àcid poli-L-làctic d'uns 30 um de diàmetre, per guiar el creixement in vitro de neurones d'explants de ganglis de l'arrel dorsal. Només el sistema biohíbrid format pel conjunt del conducte, les fibres estirades en el seu interior i la baina de cèl·lules aporta un context amigable tal que permet a les neurones créixer a taxes del mateix ordre que altres estratègies prometedores en enginyeria tissular del sistema nerviós.Vilariño Feltrer, G. (2015). Conductos de ácido hialurónico para el crecimiento axonal guiado [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/58778TESI

Impacto de las rehabilitaciones exprés sobre la pobreza energética en Valencia

El desarrollo tecnológico de España en los últimos años va unido a un fuerte incremento en la demanda de energía.Esta tendencia ha buscado solucionar el problema a través de metodologías sostenibles que aumentasen la eficiencia energética para conseguir un menor consumo en equipos, sistemas de transporte y edificios de nueva construcción. Esta realidad la podemos encontrar en el parque de viviendas de nuestro país y, las instituciones y organismos públicos, han tratado de detectar a las familias que sufren la pobreza energética con la finalidad de ofrecerles ayudas y subvenciones. Esta situación ha sido examinada y estudiada por diversos organismos, que han expuesto la realidad de muchas familias en la ciudad de València.En esta línea se presenta este libro que supone un estudio de las medidas que se podrían considerar rehabilitaciones exprés. Se analiza cómo afectan los distintos cambios que podrían realizarse en viviendas modelo y qué resultados se derivan de los mismos, permitiendo establecer una dirección clara a seguir para mejorar la calidad de vida de los ciudadanos con más dificultadesLuján Torres, C.; Moliner Galbis, J.; Rodríguez Hernández, JC.; Vilariño Feltrer, G. (2022). Impacto de las rehabilitaciones exprés sobre la pobreza energética en Valencia. Editorial Universitat Politècnica de València. https://doi.org/10.4995/UPVS.2022.61970

Materials Science Toolkit for Carbon Footprint Assessment: A Case Study for Endoscopic Accessories of Common Use

[EN] Ironically, healthcare systems are key agents in respiratory-related diseases and estimated deaths because of the high impact of their greenhouse gas emissions, along with industry, transportation, and housing. Based on safety requirements, hospitals and related services use an extensive number of consumables, most of which end up incinerated at the end of their life cycle. A thorough assessment of the carbon footprint of such devices typically requires knowing precise information about the manufacturing process, rarely available in detail because of the many materials, pieces and steps involved during the fabrication. And yet, tools most often used for determining the environmental impact of consumer goods just require a bunch of parameters, mainly based on the material composition of the device. Here we report a basic set of analytical methods that provide the information required by the software OpenLCA to calculate the main outcome related to environmental impact, the greenhouse gas emissions. Through thermogravimetry, calorimetry, infrared spectroscopy and elemental analysis we proved that obtaining relevant data for the calculator in the exemplifying case of endoscopy tooling or accessories is possible. This routine procedure opens the door to a broader, more accurate analysis of the environmental impact of everyday work at hospital services, offering potential alternatives to minimize it.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project PI21/00193 and cofunded by the European Union. Funding: Instituto de Salud Carlos III (ISCIII), PI21/00193, cofunded by the European Union. And through the project PI2023-6 from UPV-LaFe innovation projects.Martín-Cabezuelo, R.; Vilariño-Feltrer, G.; Campillo Fernandez, AJ.; Lorenzo-Zúñiga, V.; Pons, V.; López-Muñoz, P.; Tort-Ausina, I. (2023). Materials Science Toolkit for Carbon Footprint Assessment: A Case Study for Endoscopic Accessories of Common Use. ACS Environmental Au. https://doi.org/10.1021/acsenvironau.3c0004

Effect of an organotin catalyst on the physicochemical properties and biocompatibility of castor oil-based polyurethane/cellulose composites

[EN] Polyurethane/cellulose composites were synthesized from castor-oil-derived polyols and isophorone diisocyanate using dibutyltin dilaurate (DBTDL) as the catalyst. Materials were obtained by adding 2% cellulose in the form of either microcrystals (20 lm) or nanocrystals obtained by acid hydrolysis. The aim was to assess the effects of filler particle size and the use of a catalyst on the physicochemical properties and biological response of these composites. The addition of the catalyst was found to be essential to prevent filler aggregations and to enhance the tensile strength and elongation at break. The cellulose particle size influenced the composite properties, as its nanocrystals heighten hydrogen bond interactions between the filler surface and polyurethane domains, improving resistance to hydrolytic degradation. All hybrids retained cell viability, and the addition of DBTDL did not impair their biocompatibility. The samples were prone to calcification, which suggests that they could find application in the development of bioactive materials.Universidad de La Sabana supported this work under Grant No. ING-176-2016. S.V.V. acknowledges the Universidad de La Sabana for the Teaching Assistant Scholarship for his master's studies. J.A.G.T. and A.V.L. acknowledge the support of the Spanish Ministry of Economy and Competitiveness (MINECO) through project DPI2015-65401-C3-2-R (including FEDER financial support). The authors acknowledge the assistance and advice of the Electron Microscopy Service of the UPV. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Villegas-Villalobos, S.; Diaz, L.; Vilariño, G.; Vallés Lluch, A.; Gómez-Tejedor, J.; Valero, M. (2018). 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Castor oil-based polyurethanes containing cellulose nanocrystals. Polymer Engineering & Science, 51(7), 1389-1396. doi:10.1002/pen.21939Gao, Z., Peng, J., Zhong, T., Sun, J., Wang, X., & Yue, C. (2012). Biocompatible elastomer of waterborne polyurethane based on castor oil and polyethylene glycol with cellulose nanocrystals. Carbohydrate Polymers, 87(3), 2068-2075. doi:10.1016/j.carbpol.2011.10.027Cherian, B. M., Leão, A. L., de Souza, S. F., Costa, L. M. M., de Olyveira, G. M., Kottaisamy, M., … Thomas, S. (2011). Cellulose nanocomposites with nanofibres isolated from pineapple leaf fibers for medical applications. Carbohydrate Polymers, 86(4), 1790-1798. doi:10.1016/j.carbpol.2011.07.009Rocco, K. A., Maxfield, M. W., Best, C. A., Dean, E. W., & Breuer, C. K. (2014). In Vivo Applications of Electrospun Tissue-Engineered Vascular Grafts: A Review. Tissue Engineering Part B: Reviews, 20(6), 628-640. doi:10.1089/ten.teb.2014.0123Hocker, S. J. A., Hudson-Smith, N. V., Smith, P. T., Komatsu, C. H., Dickinson, L. R., Schniepp, H. C., & Kranbuehl, D. E. (2017). Graphene oxide reduces the hydrolytic degradation in polyamide-11. Polymer, 126, 248-258. doi:10.1016/j.polymer.2017.08.034Ryszkowska, J., Bil, M., Woźniak, P., Lewandowska, M., & Kurzydlowski, K. J. (2006). Influence of Catalyst Type on Biocompatibility of Polyurethanes. Materials Science Forum, 514-516, 887-891. doi:10.4028/www.scientific.net/msf.514-516.887Golomb, G., & Wagner, D. (1991). Development of a new in vitro model for studying implantable polyurethane calcification. Biomaterials, 12(4), 397-405. doi:10.1016/0142-9612(91)90008-xSantamaria-Echart, A., Ugarte, L., García-Astrain, C., Arbelaiz, A., Corcuera, M. A., & Eceiza, A. (2016). Cellulose nanocrystals reinforced environmentally-friendly waterborne polyurethane nanocomposites. Carbohydrate Polymers, 151, 1203-1209. doi:10.1016/j.carbpol.2016.06.069Gorna, K., & Gogolewski, S. (2003). 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Seguimiento del proceso de enseñanza-aprendizaje en la asignatura de transmisión de calor impartida en la Universitat Politècnica de València

[ES] El presente marco educativo universitario ha implicado el paso de una enseñanza centrada en los contenidos a una enseñanza centrada en el alumno y el desarrollo de sus capacidades. En este contexto de adaptación, resulta de vital importancia realizar un seguimiento del proceso de enseñanza-aprendizaje que permita detectar los factores que ayudan o dificultan el proceso de aprendizaje del alumno. En esta contribución se presenta el análisis del proceso de enseñanza-aprendizaje en la asignatura de transmisión de calor, impartida en el segundo año de grados de ingeniería. Se realizó una encuesta el curso 2016/2017 sobre una muestra de 139 alumnos participantes de una población total de 499 matriculados y se ha evaluado las respuestas mediante diferentes herramientas estadísticas para describir, comparar y relacionar los grupos muestrales. Los resultados revelan las características idiosincrásicas de la muestra de estudio y permiten determinar, mediante los 7 ítems analizados, la consecución de los objetivos de la asignatura, la percepción general del alumnado y la eficacia de los diferentes recursos para el aprendizaje empleados.Vilariño Feltrer, G.; Campillo Fernández, AJ.; Montagud Montalvá, CI.; Navarro Peris, E.; Payá Herrero, J.; Sarabia Escrivà, EJ. (2019). Seguimiento del proceso de enseñanza-aprendizaje en la asignatura de transmisión de calor impartida en la Universitat Politècnica de València. En INNODOCT/18. International Conference on Innovation, Documentation and Education. Editorial Universitat Politècnica de València. 775-786. https://doi.org/10.4995/INN2018.2018.8851OCS77578

Inclusión de los ODS en las asignaturas de la materia Experimentación en Ingeniería Química en el Grado en Ingeniería Química

[ES] En la presente comunicación se presenta la estrategia seguida para dar visibilidad a los Objetivos de Desarrollo Sostenible (ODS) así como poder incluirlos en las asignaturas de la materia “Experimentación en Ingeniería Química” (EIQ) del Grado en Ingeniería Química (GIQ) de la UPV, tanto para el Grado impartido en la Escuela Técnica Superior de Ingeniería Industrial (ETSII) como para el impartido en la Escuela Politécnica Superior de Alcoy (EPSA). Esta materia incluye tres asignaturas experimentales que son continuativas (Experimentación en Ingeniería Química I, II y III). Durante el primer año (curso 22-23), se hará un diagnóstico del estado actual de conocimiento e implicación que tiene el alumnado sobre los ODS a través de encuestas de opinión con la herramienta Google Drive (una encuesta a principio de curso y otra a final de curso). Además, se planteará en cada asignatura una breve sesión formativa de los ODS. Durante el segundo año (curso 23-24), se decidirán qué ODS se van a trabajar en cada asignatura y se plantearán diferentes actividades en cada una de las asignaturas incluidas en la materia Experimentación en Ingeniería Química. De la misma forma, en esta segunda anualidad, se realizarán dos encuestas (una a principio y otra a final de curso) donde se evaluará el grado de aprendizaje, adquisición e implicación del alumnado sobre los ODS.[EN] This article presents the strategy followed to give visibility to the Sustainable Development Goals (SDG) as well as to be able to include them as a part of the content of the matter "Experimentación en Ingeniería Química" of the Degree in Chemical Engineering of the Universitat Politècnica de València (UPV), both for the Degree taught at the Escuela Técnica Superior de Ingenieros Industriales (ETSII) and for the one taught at the Escuela Politécnica Superior de Alcoy (EPSA). This matter includes three experimental subjects that are continuing (Experimentación en Ingeniería Química I, Experimentación en Ingeniería Química II and Experimentación en Ingeniería Química III). During the first year (academic year 22-23) a diagnosis will be made of the current state of knowledge and involvement that students have about the SDG through opinion surveys with Google Drive tool (a survey at the beginning and another one at the end of the course). In addition, a brief training session on the SDG will be proposed in each subject. During the second year (academic year 23-24) it will be decided which SDG are going to be worked on and different activities will be proposed in each of the subjects studied. In the same way, in this second year, two surveys will be carried out (one at the beginning and the other one at the end of the course) where the degree of learning, acquisition and involvement of the students on the SDG will be evaluated.Los autores de esta comunicación agradecen a la convocatoria de Proyectos de Innovación y Mejora Educativa de la UPV 2022 y al Proyecto Docente PIME/22-23/348 con título: ''Visibilización e inclusión de los ODS en las asignaturas de la materia Experimentación en Ingeniería Química en el Grado en Ingeniería Química'' a partir del cual se basa esta publicación.Luján Facundo, MJ.; Cuartas Uribe, BE.; García Fayos, B.; Arnal Arnal, JM.; Iborra Clar, A.; Sánchez Arévalo, CM.; Rodríguez López, AD.... (2023). Inclusión de los ODS en las asignaturas de la materia Experimentación en Ingeniería Química en el Grado en Ingeniería Química. Editorial Universitat Politècnica de València. 1061-1076. https://doi.org/10.4995/INRED2023.2023.166571061107

Amphipathic Substrates Based on Crosslinker-Free Poly(ε-Caprolactone):Poly(2-Hydroxyethyl Methacrylate) Semi-Interpenetrated Networks Promote Serum Protein Adsorption

A simple procedure has been developed to synthesize uncrosslinked soluble poly(hydroxyethyl methacrylate) (PHEMA) gels, ready for use in a subsequent fabrication stage. The presence of 75 wt % methanol (MetOH) or dimethylformamide (DMF) impedes lateral hydroxyl–hydroxyl hydrogen bonds between PHEMA macromers to form during their solution polymerization at 60 °C, up to 24 h. These gels remain soluble when properly stored in closed containers under cold conditions and, when needed, yield by solvent evaporation spontaneous physically-crosslinked PHEMA adapted to the mould used. Moreover, this two-step procedure allows obtaining multicomponent systems where a stable and water-affine PHEMA network would be of interest. In particular, amphiphilic polycaprolactone (PCL):PHEMA semi-interpenetrated (sIPN) substrates have been developed, from quaternary metastable solutions in chloroform (CHCl3):MetOH 3:1 wt. and PCL ranging from 50 to 90 wt % in the polymer fraction (thus determining the composition of the solution). The coexistence of these countered molecules, uniformly distributed at the nanoscale, has proven to enhance the number and interactions of serum protein adsorbed from the acellular medium as compared to the homopolymers, the sIPN containing 80 wt % PCL showing an outstanding development. In accordance to the quaternary diagram presented, this protocol can be adapted for the development of polymer substrates, coatings or scaffolds for biomedical applications, not relying upon phase separation, such as the electrospun mats here proposed herein (12 wt % polymer solutions were used for this purpose, with PCL ranging from 50% to 100% in the polymer fraction)

Diseño de sistemas multifuncionales con aplicación en regeneración neural guiada

Consulta en la Biblioteca ETSI Industriales (8914)En este trabajo se plantea el diseño de un dispositivo formado por un sustrato polimérico cilíndrico de poros acanalados de unas pocas micras y un gel peptídico rellenando los poros, además de la comprobación empírica in vitro de la influencia que tiene cada uno de los materiales por separado y su combinación sobre la capacidad de regeneración de los axones de neuronas del sistema nervioso central. También se pretende estudiar la eficiencia de un sistema de estimulación química al crecimiento axonal a través de los poros, mediante un gradiente de concentración de moléculas activas a lo largo de los mismos y desde el extremo opuesto a la siembra celular. De esta forma se intentan exponer las bases de una estrategia, enmarcada en el campo de la Ingeniería Tisular que podría resolver el problema de la degeneración e inhabilitación de algunos sectores del encéfalo o la médula que experimentan algunas personas de manera espontánea y aparentemente irreversible, lo que se conoce como enfermedades neurodegenerativas, cuyo origen está constantemente en discusión y cuya solución aún se desconoce.Vilariño Feltrer, G. (2011). Diseño de sistemas multifuncionales con aplicación en regeneración neural guiada. http://hdl.handle.net/10251/29224.Archivo delegad

Development and evaluation of hyaluronan nanocomposite conduits for neural tissue regeneration

[EN] Hyaluronan-based hydrogels are among the most promising neural tissue engineering materials because of their biocompatibility and the immunomodulation capabilities of their degradation byproducts. Despite these features, the problems related to their handling and mechanical properties have not yet been solved. In the present work it is proposed to address these drawbacks through the development of nanohybrid materials in which different nanometric phases (carbon nanotubes, mesoporous silica nanoparticles) are embedded in a crosslinked hyaluronan matrix. These nanohybrid matrices were next processed in the shape of cylindrical conduits aimed at promoting and improving neural stem cell differentiation and regeneration in neural tracts. These constructs could be of use specifically for peripheral nerve regeneration. Results of the study show that the inclusion of the different phases improved physico-chemical features of the gel such as its relative electrical permittivity, water intake and elastic modulus, giving hints on how the nanometric phase interacts with hyaluronan in the composite as well as for their potential in combined therapeutic approaches. Regarding the in vitro biological behavior of the hybrid tubular scaffolds, an improved early cell adhesion and survival of Schwann cells in their lumen was found, as compared to conduits made of pure hyaluronan gels. Furthermore, the differentiation and survival of neural precursors was not compromised, despite alleged safety concerns.The authors acknowledge funding through the MAT2011-28791-C03-02,03 project from the Spanish Ministerio de Economia y Competitividad. The authors thank deeply the advice of C. Martinez Ramos, Ph.D. on the cell culture tasks, Prof. J. M. Meseguer Duenas on the dielectric impedance spectroscopy, and S. Ivaschenko with FTIR spectroscopy. Lastly, Prof. P. Amoros from Institut de Ciencia de Materials of Universitat de Valencia (ICMUV) and Prof. J. M. Verdugo are thanked for providing the mesoporous silica nanoparticles and the rat neurospheres, respectively. The Electronic Microscopy Service of the Universitat Politecnica de Valencia is acknowledged their help and dedication.Mullor Ruiz, I.; Vilariño-Feltrer, G.; Mnatsakanyan, H.; Vallés Lluch, A.; Monleón Pradas, M. (2021). Development and evaluation of hyaluronan nanocomposite conduits for neural tissue regeneration. Journal of Biomaterials Science Polymer Edition. 32(17):2227-2245. https://doi.org/10.1080/09205063.2021.1963930S22272245321

Unveiling the Role of Key Parameters during Molecular Growth for Optimal Poly(glycerol sebacate) Synthesis

Abstract Poly(glycerol sebacate) (PGS) belongs to the hyperbranched polyesters family (HBP), which possesses an extensive variety of applications due to its tunable chemical and mechanical properties, together with its biocompatibility and biodegradability. However, the understanding of PGS synthesis becomes a challenge due to the lack of consistency when determining its synthesis parameters. Understanding these parameters is fundamental to control PGS synthesis and obtain a scalable and reproducible final product for biomedical applications. To unveil their effect on diverging PGS properties, diols are used as glycerol analogs and the reaction is chemically and thermally monitored, suggesting a heterogeneous reactivity of the exposed hydroxyl groups. Also, confinement of the prepolymerization is proven to be fundamental In order to maintain the equimolar ratio of initial monomers during synthesis. Early stages of the polycondensation (first 4 h) tend to linear and less branched oligomers by consuming primary hydroxyls rather than secondary hydroxyls. However, physicochemical characterization determines that a high degree of conversion (40%) is reached during these early stages. Afterward, the oligomers tend to condense through the secondary hydroxyls into a more crosslinked elastomer. This study demonstrates how hydroxyl affinity, water presence, and glycerol loss are crucial for the scalability and reproducibility of its final product