The bony biochemical environment is a complex system that permits and promotes cellular functions that lead to matrix production and ossification. In Part I of this review, we discussed the important actions of signaling molecules, including hormones, cytokines, and growth factors. Here, we review other constituents of the extracellular matrix, including minerals, fibrinous and nonfibrinous proteins, and enzymes such as the matrix metalloproteinases. We conclude with a discussion of the role of biochemical modulation in endogenous and exogenous tissue engineering.

Background. Bone engineering requires thicker three-dimensional constructs than the maximum thickness supported by standard cell-culture techniques (2 mm). A flow-perfusion bioreactor was developed to provide chemotransportation to thick (6 mm) scaffolds. Methods. Polyurethane scaffolds, seeded with murine preosteoblasts, were loaded into a novel bioreactor. Control scaffolds remained in static culture. Samples were harvested at days 2, 4, 6, and 8 and analyzed for cellular distribution, viability, metabolic activity, and density at the periphery and core. Results. By day 8, static scaffolds had a periphery cell density of 67% ± 5.0%, while in the core it was 0.3% ± 0.3%. Flow-perfused scaffolds demonstrated peripheral cell density of 94% ± 8.3% and core density of 76% ± 3.1% at day 8. Conclusions. Flow perfusion provides chemotransportation to thick scaffolds. This system may permit high throughput study of 3D tissues in vitro and enable prefabrication of biological constructs large enough to solve clinical problems.

While it has been long appreciated that biomechanical forces are involved in bone remodeling and repair, the actual mechanism by which a physical force is translated to the corresponding intracellular signal has largely remained a mystery. To date, most biomechanical research has concentrated upon the effect on bone morphology and architecture, and it is only recently that the complex cellular and molecular pathways involved in this process (called mechanotransduction) are being described. In this paper, we review the current understanding of bone mechanobiology and highlight the implications for clinical medicine and tissue engineering research.