Application of different strain regimes in two-dimensional and three-dimensional adipose tissue-derived stem cell cultures induces osteogenesis: implications for bone tissue engineering

Mechanical strain has become an important tool in tissue engineering for progenitor cell differentiation. Furthermore, it is used to enhance the mechanical properties of engineered tissue constructs. Although strain amplitude and frequency are well investigated and optimal values are known; application of various strain schemes regarding duration and repetition are not described in literature. In this study, we therefore applied singular and repetitive cyclic strain (1 Hz, 5%) of 15 min short-time strain and longer strain durations up to 8 h. Additionally, a gradually increasing strain scheme starting with short-time strain and consecutive elongated strain periods was applied. The cultivation surface was planar silicone on one hand and a three-dimensionally structured collagen I mesh on the other hand. Adipose tissue-derived mesenchymal stem cells and an osteogenic model cell line (MG-63) were exposed to these strain regimes and post-strain cell viability, osteogenic marker gene expression, and matrix mineralization were investigated. Upregulation of alkaline phosphatase, osteocalcin, osteopontin, and BMP-2/4 revealed that even short-time strain can enhance osteogenic differentiation. Elongation and repetition of strain, however, resulted in a decline of the observed short-time strain effects, which we interpret as positively induced cellular adaptation to the mechanically active surroundings. With regard to cellular adaptation, the gradually increasing strain scheme was especially advantageous.