An integrated experimental–computational approach for the study of engineered cartilage constructs subjected to combined regimens of hydrostatic pressure and interstitial perfusion

• Published in: Bio-medical materials and engineering Vol. 18; no. 4-5; pp. 273 - 278
• Main Authors: Moretti, M., Freed, L.E., Padera, R.F., Laganà, K., Boschetti, F., Raimondi, M.T.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2008
• Subjects: Animals; Bioreactors; Cartilage - cytology; Cartilage - physiology; Cattle; Cells, Cultured; Chondrocytes - cytology; Chondrocytes - physiology; Equipment Design; Equipment Failure Analysis; Mechanotransduction, Cellular - physiology; Organ Culture Techniques - instrumentation; Organ Culture Techniques - methods; Perfusion - instrumentation; Perfusion - methods; Pressure; Systems Integration; Tissue Engineering - instrumentation; Tissue Engineering - methods
• ISSN: 0959-2989; 1878-3619
• DOI: 10.3233/BME-2008-0536

Tissue engineering is a rapidly emerging collection of technologies aimed at the regeneration of diseased and injured tissues and organs by implantation of cells combined with biomaterial scaffolds. Articular cartilage has a very limited intrinsic healing potential and cartilage lesions can ultimately lead to osteoarthritis and to prosthesis application. To overcome these limitations, cartilage tissue engineering has emerged as a clinically significant and innovative field of research. Under physiological conditions, natural cartilage is subject to complex mechanical stimulation during dynamic loading, wherein shear stress and interstitial pressure act simultaneously on the tissue and its component chondrocytes. In vitro studies have shown that mechanical stimuli such as compression, fluid flow and hydrostatic pressure can regulate cartilage metabolism and enhance chondrogenesis, and bioreactor systems, which can provide reproducible and controlled changes of specific environmental factors, represent valuable tools for investigating how mechanical stimuli affect production of ECM by cultured chondrocytes, and for defining and optimizing mechanical stimuli required to generate a high quality cartilage substitute in vitro. Interstitial fluid flow is one important mechanical signal, as it can modulate cellular alignment, shape, and ECM synthesis and deposition. For example, interstitial fluid flow, applied by direct perfusion of three-dimensional (3D) engineered cartilage constructs, was shown to enhance extracellular matrix (ECM) synthesis. Hydrostatic pressure is another important mechanical signal, as it can also modulate cell shape and ECM deposition. Hydrostatic pressure was shown to increase ECM by cultured chondrocytes when applied intermittently and maintained within the physiological range. Importantly, the effects of fluid flow and hydrostatic pressure on chondrogenesis were shown to depend on the duration and amplitude of the applied stimulation and cell type used. However, bioreactors have typically been used to study the effect of a single physical parameter, which can be an advantage because of the complexity intrinsic to cell mechanobiology, but can also be a limitation since multiple stimuli applied a combination can result in an engineered tissues with better mechanical and biochemical properties than a single applied stimulus. Moreover, the environment to which cells cultured within 3D tissue engineered constructs is often complex, and not well understood or controllable. Hence, computational fluid dynamics (CFD) represents a powerful and cost-effective tool for designing and optimizing tissue engineering systems at the macro-scale (i.e. the bioreactor) and also the micro-scale (the scaffold micro-geometry).