Kelvin W. Li

Growth responses of cartilage to static and dynamic compression.

During skeletal development, growth, and maturation, gradual changes in the material properties and physical dimensions of cartilage occur under the influence of mechanical loading. The objective of the current study was to compare glycosaminoglycan biosynthesis and cell proliferation in fetal, calf, and adult bovine cartilage explants, isolated from defined depths from the articular surface, in response to controlled compressive loads. Mechanical testing confirmed that for all cartilage samples subjected to load, there was a marked time-averaged (static) compression, whereas the addition of dynamic load at a frequency of 0.01 Hz induced dynamic strain with amplitude and phase shift characteristics typical of stimuli that previously were found to be associated with stimulation of glycosaminoglycan synthesis. In metabolic studies, the application of static loading (84 kPa) for 24 hours inhibited glycosaminoglycan and deoxyribonucleic acid synthesis in all cultured cartilage samples. The superposition of dynamic loading (200 kPa, 0.01 Hz) induced a 20% stimulation of glycosaminoglycan biosynthesis in calf cartilage from the middle-deep zones over statically-loaded samples and an additional approximate 50% suppression of deoxyribonucleic acid synthesis in fetal and calf cartilage from the articular surface. These results indicate that synthesis of glycosaminoglycan and deoxyribonucleic acid, two distinct indices of cartilage growth, are regulated independently by mechanical loading and that cartilage responds differently to static and dynamic loading at different stages of maturation.

In Vitro Physical Stimulation of Tissue-Engineered and Native Cartilage

Because of the limited availability of donor cartilage for resurfacing defects in articular surfaces, there is tremendous interest in the in vitro bioengineering of cartilage replacements for clinical applications. However, attaining mechanical properties in engineered cartilaginous constructs that approach those of native cartilage has not been previously achieved when constructs are cultured under free-swelling conditions. One approach toward stimulating the development of constructs that are mechanically more robust is to expose them to physical environments that are similar, in certain ways, to those encountered by native cartilage. This is a strategy motivated by observations in numerous short-term experiments that certain mechanical signals are potent stimulators of cartilage metabolism. On the other hand, excess mechanical loading can have a deleterious effect on cartilage. Culture conditions that include a physical stimulation component are made possible by the use of specialized bioreactors. This chapter addresses some of the issues involved in using bioreactors as integral components of cartilage tissue engineering and in studying the physical regulation of cartilage. We first consider the generation of cartilaginous constructs in vitro. Next we describe the rationale and design of bioreactors that can impart either mechanical deformation or fluid-induced mechanical signals.