Increased extracellular Ca2+ concentrations are potent chemical signals for cell migration and directed growth [59] and [60], as well as homing signals that bring together Autophagy Compound Library cell line the different cell types required for the initiation of

bone remodeling [61]. Pi is also a regulator of osteoblast proliferation and differentiation [62], and the high concentration of Pi in the microenvironment induced osteoblast apoptosis in vitro [63] and the in vivo mineralization of the bone matrix [64]. Moreover, specific Ca2+ and Pi concentrations have been suggested to induce the higher proliferation and osteogenic differentiation of MSC [65]. CaP bioceramics appear to be candidates for scaffold-aimed bone tissue engineering because they can release inorganic ions during dissolution. As discussed above, many factors are associated with mimicking of the cell niche/microenvironment to enforce regeneration by the application of tissue engineering. Not only scaffold properties

affect stem cell functions; cells can also induce the deformation and degradation of scaffolds during the process of regeneration, leading to the altered mechanical properties of scaffolds (Fig. 3). Thus, the cell–scaffold interplay is bidirectional and involves a feedback loop of cells and scaffolds. Forces are generated in the context of cell adhesion to ECM/scaffolds, and mechanotransduction occurs to transduce them click here into intracellular signals that drive functional modulations in cells: proliferation, differentiation, migration,

and apoptosis [55]. The actin cytoskeleton plays the most prominent role in these events [66]. Human MSC also express specific transcription factors of mechanotransduction and undergo tissue-specific cell fate switches when cultured on ECMs with mechanical stiffness mirroring the physical properties of respective specific tissue [67]. To ADP ribosylation factor instruct stem cells and modify their fates, scaffold biomaterial should provide informative microenvironments mimicking a physiological niche of the target tissue. Biomaterials can have a suitable design to transmit specific signals to cells that can be decoded into biochemical signals depending on its composition and processing methods. Both biophysical and biochemical cues have been involved in cell–ECM interactions in nature. Hence, topography, chemistry and physical properties are involved and are critical for determining cell fate [68]. To accomplish the desirable interplay between cells, biomaterial designing should include parameters within (a) surface, (b) mechanical, (c) morphological, and (d) electrical properties (Fig. 3). Surface topography and chemical composition were able to drive cell adhesion, proliferation, migration, and differentiation [55], [69] and [70].