Response of musculoskeletal cells to biomaterials

Many of our current therapies are based on information obtained in cell cultures using substrates that have little in common with the substrates the cells will encounter in vivo. To produce materials that are clinically valuable, we must analyze more deeply how musculoskeletal cells interact with the physical features of their environments. An increasing body of information has examined the mechanisms by which osteoblasts interact with their substrate. The underlying substrate, particularly in bone, also has structural features that can alter the mechanical environment experienced by the cells. These structural features modulate the nature of cell attachment and the resulting cell shape, affecting cell proliferation and differentiation. The chemistry, surface energy, and microarchitecture of a material all influence the kinds of proteins that adsorb onto the surface, which in turn affects integrin-mediated attachment. Signaling via integrins initiates the transfer of information to the cell about the microenvironment. Cells can differentiate between crystallinities of the same chemistry and distinguish complex differences in surface structure. These differences in the in vitro response correspond to differences in clinical effectiveness. By designing biomaterials that maximally enhance mesenchymal cell attachment, migration, proliferation, and differentiation, the value of these materials for tissue repair will be markedly increased. The goal is to provide materials that are capable of supporting tissue regeneration in vivo, often at sites compromised by infection and loss of structure.