Bioreactor configurations for adventitious root culture: recent advances toward the commercial production of specialized metabolites.

In vitro plant cell and organ cultures are appealing alternatives to traditional methods of producing valuable specialized metabolites for use as: pharmaceuticals, food additives, cosmetics, perfumes, and agricultural chemicals. Cell cultures have been adopted for the production of specialized metabolites in certain plants. However, in certain other systems, adventitious roots are superior to cell suspension cultures as they are organized structures that accumulate high levels of specialized metabolites. The cultivation of adventitious roots has been investigated in various bioreactor systems, including: mechanically agitated, pneumatically agitated, and modified bioreactors. The main relevance and importance of this work are to develop a long-lasting industrial biotechnological technology as well as to improve the synthesis of these metabolites from the plant in vitro systems. These challenges are exacerbated by: the peculiarities of plant cell metabolism, the complexity of specialized metabolite pathways, the proper selection of bioreactor systems, and bioprocess optimization. This review's major objective is to analyze several bioreactor types for the development of adventitious roots, as well as the advantages and disadvantages of each type of bioreactor, and to describe the strategies used to increase the synthesis of specialized metabolites. This review also emphasizes current advancements in the field, and successful instances of scaled-up cultures and the generation of specialized metabolites for commercial purposes are also covered.

Suspension culture of somatic embryos for the production of high-value secondary metabolites.

Secondary metabolites from plants are ubiquitous and have applications in medicines, food additives, scents, colorants, and natural pesticides. Biotechnological production of secondary metabolites that have economic benefits is an attractive alternative to conventional methods. Cell, adventitious, and hairy root suspension cultures are typically used to produce secondary metabolites. According to recent studies, somatic embryos in suspension culture are useful tools for the generation of secondary metabolites. Somatic embryogenesis is a mode of regeneration in several plant species. This review provides an update on the use of somatic embryogenesis in the production of valuable secondary metabolites. The factors influencing the generation of secondary metabolites using somatic embryos in suspension cultures, elicitation methods, and prospective applications are also discussed in this review.

Photobioreactor configurations in cultivating microalgae biomass for biorefinery.

Microalgae, highly prized for their protein, lipid, carbohydrate, phycocyanin, and carotenoid-rich biomass, have garnered significant industrial attention in the context of third-generation (3G) biorefineries, seeking sustainable alternatives to non-renewable resources. Two primarily cultivation methods, open ponds and closed photobioreactors systems, have emerged. Open ponds, favored for their cost-effectiveness in large-scale industrial production, although lacking precise environmental control, contrast with closed photobioreactors, offering controlled conditions and enhanced biomass production at the laboratory scale. However, their high operational costs challenge large-scale deployment. This review comprehensively examines the strength, weakness, and typical designs of both outdoor and indoor microalgae cultivation systems, with an emphasis on their application in terms of biorefinery concept. Additionally, it incorporates techno-economic analyses, providing insights into the financial aspects of microalgae biomass production. These multifaceted insights, encompassing both technological and economic dimensions, are important as the global interest in harnessing microalgae's valuable resources continue to grow.

Enhanced Stability of Oral Vitamin C Delivery: A Novel Large-Scale Method for Liposomes Production and Encapsulation through Dynamic High-Pressure Microfluidization.

In recent years, nanocarriers have been widely used as an effective solution for oral administration of pharmaceuticals. However, there is still an urgent need to speed up their translation to clinical practice. Cost-effective and industrially scalable methodologies are still needed. Herein, the production of vitamin C-loaded liposomes for nutraceutical purposes has been investigated and optimized by adopting a High-Pressure Homogenizer. Initially, the impact of process parameters on particles size, distributions, and morphology was explored. The findings document that the pressure and cycle manipulation allow for control over liposome size and polydispersity, reaching a maximum encapsulation efficiency exceeding 80%. This significantly improves the storage stability of vitamin C, as demonstrated by monitoring its antioxidant activity. Furthermore, the in vitro simulation of gastrointestinal digestion shows that liposomes could protect the active substance from damage and control its release in the gastrointestinal fluid. Thus, the whole nanodelivery system can contribute to enhancing vitamin C bioavailability. In conclusion, the results indicate that this innovative approach to producing vitamin C liposomes holds promise for clinical translation and industrial scale-up. Indeed, by utilizing food-grade materials and straightforward equipment, it is possible to produce stable and functional liposomes suitable for health products.

Upscaling the urea method synthesis of CoAl layered double hydroxides.

Research on two-dimensional materials is one of the most relevant fields in materials science. Layered double hydroxides (LDHs), a versatile class of anionic clays, exhibit great potential in photocatalysis, energy storage and conversion, and environmental applications. However, its implementation in real-life devices requires the development of efficient and reproducible large-scale synthesis processes. Unfortunately, reliable methods that allow for the production of large quantities of two-dimensional LDHs with well-defined morphologies and high crystallinity are very scarce. In this work, we carry out a scale-up of the urea-based CoAl-LDH synthesis method. We thoroughly study the effects of the mass scale-up (25-fold: up to 375 mM) and the volumetric scale-up (20-fold: up to 2 L). For this, we use a combination of several structural (XRD, TGA, and N2 and CO2 isotherms), microscopic (SEM, TEM, and AFM), magnetic (SQUID), and spectroscopic techniques (ATR-FTIR, UV-vis, XPS, ICP-MS, and XANES-EXAFS). In the case of the volumetric scale-up, a reduction of 45% in the lateral dimensions of the crystals (from 3.7 to 2.0 µm) is observed as the reaction volume increases. This fact is related to modified heating processes affecting the alkalinization rates and, concomitantly, the precipitation, even under recrystallization at high temperatures. In contrast, for the tenfold mass scale-up, similar morphological features were observed and assigned to changes in nucleation and growth. However, at higher concentrations, simonkolleite-like Co-based layered hydroxide impurities are formed, indicating a phase competition during the precipitation related to the thermodynamic stability of the growing phases. Overall, this work demonstrates that it is possible to upscale the synthesis of high-quality hexagonal CoAl-LDH in a reproducible manner. It highlights the most critical synthesis aspects that must be controlled and provides various fingerprints to trace the quality of these materials. These results will contribute to bringing the use of these 2D layered materials closer to reality in different applications of interest.

Alternative activated/KOH adsorbent for phenol adsorption: experimental, industrial case study and mass transfer interpretation.

Removal of phenol from wastewater is essential to achieve permitted concentrations according to the recommendations of USEPA. The adsorption capacity of phenol in activated adsorbent with KOH of Enterolobium contortisiliquum (TAC) was evaluated at different temperatures. The Langmuir isotherm represented the equilibrium data of this study. Thermodynamic process was endothermic, spontaneous, and reversible. The mass transfer parameters ranged from KE 0.68 to 0.96 × 10-3 (cm s-1), Ds 8.95 to 14.35 × 10-9 (cm2 s-1), and Dp 5.023 × 10-8 (cm2 s-1). The PVSDM model represented the adsorption kinetics. Intraparticle diffusion limits the mass transfer process Biot > 100. The two-stage process minimized the total amount of TAC required to achieve the permitted specification of phenol concentration in wastewater from different industrial sectors. TAC showed significant performance in the removal of phenol from wastewater.

A scale-up strategy for the synthesis of chitosan derivatives used in micellar nanomedicines.

Nanomedicines have been increasingly investigated and used by pharmaceutical industry due to their potential in solving various public health problems. However, standardizing and approving nanomedicines remains a significant challenge, as the translation from the laboratory to the market is still limited. These constraints are due to a lack of reproducibility and standardization of procedures, small batch sizes due to inability to scale-up, or the associated production costs as a result of the production methods chosen. In this work, two chitosan derivatives, methoxypolyethylene glycol-chitosan (mPEG-CS) and methoxypolyethylene glycol-chitosan-oleic acid (mPEG-CS-OA), produced at the lab scale were implemented in a pharmaceutical industry to achieve the scale-up production using cross flow filtration (CFF). The two copolymers were shown to be capable of retaining their physicochemical properties when produced in larger batch sizes, with reduced production time and increased yield. Also, both chitosan derivatives presented no in vitro cytotoxicity independent of the method of production. Furthermore, after scale-up, polymeric micelles produced from mPEG-CS-OA were tested for storage stability, demonstrating that micelles remained stable at - 20 °C for at least 6 months. This study demonstrated the feasibility of producing polymers and polymeric micelles closer to the bedside due to their suitability for GMP production.

Bio-based rhamnolipids production and recovery from waste streams: Status and perspectives.

Bio-based rhamnolipid production from waste streams is gaining momentum nowadays because of increasing market demand, huge range of applications and its economic and environment friendly nature. Rhamnolipid type biosurfactants are produced by microorganisms as secondary metabolites and have been used to reduce surface/interfacial tension between two different phases. Biosurfactants have been reported to be used as an alternative to chemical surfactants. Pseudomonas sp. has been frequently used for production of rhamnolipid. Various wastes can be used in production of rhamnolipid. Rhamnolipids are widely used in various industrial applications. The present review provides information about structure and nature of rhamnolipid, production using different waste materials and scale-up of rhamnolipid production. It also provides comprehensive literature on various industrial applications along with perspectives and challenges in this research area.

Spark Plasma Sintering of Aluminum Nanocomposite Powders: Recent Strategy to Translate from Lab-Scale to Mass Production.

The aim of this paper focuses on presenting a recent study that describes the fundamental steps needed to effectively scale-up from lab to mass production parts produced from Al powders reinforced with 0.5 wt% of industrial multiwalled carbon nanotubes (MWCNTs), with mechanical and electrical conductivity properties higher that those measured at the lab scale. The produced material samples were produced via a Spark Plasma Sintering (SPS) process using nanocomposite aluminum powders elaborated with a planetary ball-mill at the lab scale, and high-volume attrition milling equipment in combination with controlled atmosphere sinter hardening furnace equipment, which were used to consolidate the material at the industrial level. Surprisingly, the electrical conductivity and mechanical properties of the samples produced with the reinforced nanocomposite Al powders were made with mass production equipment and were similar or higher than those samples fabricated using metallic powders prepared with ball-mill lab equipment. Experimental measurements show that the hardness and the electrical conductivity properties of the samples fabricated with the mass production Al powders are 48% and 7.5% higher than those of the produced lab samples. This paper elucidates the steps that one needs to follow during the mass production process of reinforced aluminum powders to improve the physical properties of metallic samples consolidated via the SPS process.

Engineering of Escherichia coli strains for plasmid biopharmaceutical production: scale-up challenges.

Plasmid-based vaccines and therapeutics have been making their way into the clinic in the last years. The existence of cost-effective manufacturing processes capable of delivering high amounts of high-quality plasmid DNA (pDNA) is essential to generate enough material for trials and support future commercialization. However, the development of pDNA manufacturing processes is often hampered by difficulties in predicting process scale performance of Escherichia coli cultivation on the basis of results obtained at lab scale. This paper reports on the differences observed in pDNA production when using shake flask and bench-scale bioreactor cultivation of E. coli strains MG1655ΔendAΔrecA and DH5α in complex media with 20 g/L of glucose. MG1655ΔendAΔrecA produced 5-fold more pDNA (9.8 mg/g DCW) in bioreactor than in shake flask (1.9 mg/g DCW) and DH5α produced 4-fold more pDNA (8 mg/g DCW) in bioreactor than in shake flask (2 mg/g DCW). Accumulation of acetate was also significant in shake flasks but not in bioreactors, a fact that was attributed to a lack of control of pH.