ABSTRACT
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.
Subject(s)
Regenerative Medicine/trends , Tissue Engineering/trends , Cell Physiological Phenomena , Humans , Models, TheoreticalABSTRACT
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.
Subject(s)
Extracellular Matrix/chemistry , Mesenchymal Stem Cells/cytology , Models, Theoretical , Tissue Engineering/methods , Tissue Scaffolds , Animals , Electroplating , HumansABSTRACT
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.
Subject(s)
Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/physiology , Models, Biological , Tissue Engineering/methods , Animals , Cell Adhesion , Cell Death , Cell Differentiation , Cell Movement , Cell Proliferation , Cell Self Renewal , Extracellular Matrix/metabolism , Humans , Mathematical Concepts , Mesenchymal Stem Cell Transplantation/statistics & numerical data , Neovascularization, Physiologic , Tissue Engineering/statistics & numerical data , Tissue Scaffolds/statistics & numerical dataABSTRACT
AIM: Scaffolds are a promising approach for spinal cord injury (SCI) treatment. FGF-2 is involved in tissue repair but is easily degradable and presents collateral effects in systemic administration. In order to address the stability issue and avoid the systemic effects, FGF-2 was encapsulated into core-shell microfibers by coaxial electrospinning and its in vitro and in vivo potential were studied. Materials & methods: The fibers were characterized by physicochemical and biological parameters. The scaffolds were implanted in a hemisection SCI rat model. Locomotor test was performed weekly for 6 weeks. After this time, histological analyses were performed and expression of nestin and GFAP was quantified by flow cytometry. Results: Electrospinning resulted in uniform microfibers with a core-shell structure, with a sustained liberation of FGF-2 from the fibers. The fibers supported PC12 cells adhesion and proliferation. Implanted scaffolds into SCI promoted locomotor recovery at 28 days after injury and reduced GFAP expression. CONCLUSION: These results indicate the potential of these microfibers in SCI tissue engineering. [Formula: see text].