Modification of the Luedeking and Piret model with a delay time parameter for biotechnological lactic acid production.

OBJECTIVES: To obtain a mathematical model that adequately describes the time lag between biomass generation and lactic acid production of lactic fermentations. METHODS: Seven experimental kinetics from other research works were studied to validate our proposal: four studies of Fungal Submerged Fermentation and three cases of Bacterial Submerged Fermentation, including the data recollected by Luedeking and Piret. RESULTS: We introduce a modification to the Luedeking and Piret model that consist in the introduction of a time delay parameter in the model, this parameter would account for the lag time that exists between the production of biomass and lactic acid. It is possible to determine this time delay in a simple way by approximating the biomass and product formation considering that they behave as a first order plus dead time system. The duration of this phenomenon, which is not described with the classical Luedeking and Piret model, is a function of microorganism physiology (ease of biomass growth), environment (nutrients) and type of inoculum. CONCLUSION: The Luedeking and Piret with delay model applications reveal an increase of the R2 in all cases, evidencing the quality of fit and the simplicity of the method proposed. These model would improve the accuracy of bioprocess scaling up.

Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma.

A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells was demonstrated. Convection-enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ-bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma. FROM THE CLINICAL EDITOR: GBM remains one of the most notoriously treatment-unresponsive cancer types. In this study, a multifunctional nanoparticle-based temozolomide delivery system was demonstrated to possess enhanced treatment efficacy in a rodent xenograft GBM model, with the added benefit of MRI-based tracking via the incorporation of iron oxide as a T2* contrast material in the nanoparticles.

Effect of fiber diameter on the spreading, proliferation and differentiation of chondrocytes on electrospun chitosan matrices.

Tissue-engineered neocartilage with appropriate biomechanical properties holds promise not only for graft applications but also as a model system for controlled studies of chondrogenesis. Our objective in the present research study is to better understand the impact of fiber diameter on the cellular activity of chondrocytes cultured on nanofibrous matrices. By using the electrospinning process, fibrous scaffolds with fiber diameters ranging from 300 nm to 1 µm were prepared and the physicomechanical properties of the scaffolds were characterized. Bovine articular chondrocytes were then seeded and maintained on the scaffolds for 7 and 14 days in culture. An upregulation in the gene expression of collagen II was noted with decreasing fiber diameters. For cells that were cultured on scaffolds with a mean fiber diameter of 300 nm, a 2-fold higher ratio of collagen II/collagen I was noted when compared to cells cultured on sponge-like scaffolds prepared by freeze drying and lyophilization. Integrin (α(5), αv, ß(1)) gene expression was also observed to be influenced by matrix morphology. Our combined results suggest that matrix geometry can regulate and promote the retention of the chondrocyte genotype.

The effect of ultrasound stimulation on the gene and protein expression of chondrocytes seeded in chitosan scaffolds.

Both pulsed- and square-wave, low-intensity ultrasound (US) signals have been reported to impact chondrocyte function and biosynthetic activity. In this study, a low-intensity diffuse ultrasound (LIDUS) signal at 5.0 MHz (0.14 mW/cm(2)) was employed to stimulate bovine chondrocytes seeded in three-dimensional (3D) chitosan-based matrices. While the duration of application was constant at 51 s, US was applied once, twice, four times and eight times/day, and the impacts of US on the biosynthetic activity of chondrocytes and the expression of chondrocyte-specific genes were evaluated. When stimulated with continuous US for predetermined time intervals, chondrocytes had higher levels of type II collagen, aggrecan, L-Sox5 and Sox9 mRNA expression when compared to controls; however, under the same conditions, the expression of MMP-3 was downregulated. Interestingly, both Sox5 and Sox9 genes coordinately responded to changes in US stimulation and generally mirrored the response of collagen type II transcript to changes in US stimulation. RT-PCR analysis revealed that US stimulation increased the gene expression of cell-surface integrins α5 and ß1. The expression of integrins α2 was downregulated by US treatment, suggesting that multiple integrin subunits may be involved in the regulation of chondrocytic function in response to US stimuli. The enhancement in the abundance of the mRNA transcripts upon US stimulation was observed to correlate with the protein expression of collagen type I, collagen type II, and integrins α5 and ß1. In conclusion, the US stimulation regimen employed was shown to modulate the proliferative capacity, biosynthetic activity and integrin mRNA expression of articular chondrocytes maintained in 3D matrices.