Process System Engineering Methodologies Applied to Tissue Development and Regenerative Medicine.

Tissue engineering and the manufacturing of regenerative medicine products demand strict control over the production process and product quality monitoring. In this chapter, the application of process systems engineering (PSE) approaches in the production of cell-based products has been discussed. Mechanistic, empirical, continuum and discrete models are compared and their use in describing cellular phenomena is reviewed. In addition, model-based optimization strategies employed in the field of tissue engineering and regenerative medicine are discussed. An introduction to process control theory is given and the main applications of classical and advanced methods in cellular production processes are described. Finally, new nondestructive and noninvasive monitoring techniques have been reviewed, focusing on large-scale manufacturing systems for cell-based constructs and therapeutic products. The application of the PSE methodologies presented here offers a promising alternative to overcome the main challenges in manufacturing engineered tissue and regeneration products.

Relevant biological processes for tissue development with stem cells and their mechanistic modeling: A review.

A potential alternative for tissue transplants is tissue engineering, in which the interaction of cells and biomaterials can be optimized. Tissue development in vitro depends on the complex interaction of several biological processes such as extracellular matrix synthesis, vascularization and cell proliferation, adhesion, migration, death, and differentiation. The complexity of an individual phenomenon or of the combination of these processes can be studied with phenomenological modeling techniques. This work reviews the main biological phenomena in tissue development and their mathematical modeling, focusing on mesenchymal stem cell growth in three-dimensional scaffolds.

Mesenchymal stem cell cultivation in electrospun scaffolds: mechanistic modeling for tissue engineering.

Tissue engineering is a multidisciplinary field of research in which the cells, biomaterials, and processes can be optimized to develop a tissue substitute. Three-dimensional (3D) architectural features from electrospun scaffolds, such as porosity, tortuosity, fiber diameter, pore size, and interconnectivity have a great impact on cell behavior. Regarding tissue development in vitro, culture conditions such as pH, osmolality, temperature, nutrient, and metabolite concentrations dictate cell viability inside the constructs. The effect of different electrospun scaffold properties, bioreactor designs, mesenchymal stem cell culture parameters, and seeding techniques on cell behavior can be studied individually or combined with phenomenological modeling techniques. This work reviews the main culture and scaffold factors that affect tissue development in vitro regarding the culture of cells inside 3D matrices. The mathematical modeling of the relationship between these factors and cell behavior inside 3D constructs has also been critically reviewed, focusing on mesenchymal stem cell culture in electrospun scaffolds.

Interactions between soy protein from water-soluble soy extract and polysaccharides in solutions with polydextrose.

This study focuses on the investigation of the interactions between polysaccharides (carrageenan and carboxymethylcellulose--CMC) and soy proteins from the water-soluble soy extract. The influence of pH (2-7) and protein-polysaccharide ratio (5:1-40:1) on the interaction between these polyelectrolytes was investigated in aqueous solutions with 10% of polydextrose and without polydextrose. The studied systems were analyzed in terms of pH-solubility profile of protein, ζ-potential, methylene blue-polysaccharide interactions, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and confocal laser scanning microscopy. Although the mixtures of soy extract with both carrageenan and CMC showed dependency on the pH and protein-polysaccharide ratio, they did not present the same behavior. Both polysaccharides modified the pH-solubility profile of the soy protein, shifting the pH range in which the coacervate is formed to a lower pH region with the decrease of the soy extract-polysaccharide ratio. The samples also presented detectable differences regarding to ζ-potential, DSC, FTIR and microscopy analyses. The complex formation was also detected even in a pH range where both biopolymers were net-negatively charged. The changes promoted by the presence of polydextrose were mainly detected by blue-polysaccharide interactions measures and confocal microscopy.

Alexithymia and neuroendocrine-immune response in patients with autoimmune diseases: preliminary results on relationship between alexithymic construct and TNF-alpha levels.

Alexithymia is conceptualized as a disorder of emotion regulation mechanisms, which involves a dissociation of emotional and physical responses to life events and bodily sensations. Our results might suggest a possible relationship between the alexithymic construct and TNF levels in RA patients. These preliminary findings corroborate the integrated bidirectional interactions between neuropsychological mechanisms and the neuroendocrine-immune system in patients affected by autoimmune diseases and contribute to finding a common biological pathway linking alexithymia and autoimmune-inflammatory diseases.