Physical and chemical modifications of surface properties lead to alterations in osteoblast behavior.

摘要

Proper formation of the bone extracellular matrix (ECM), or osteoid, depends on the surface properties of pre-existing tissue and the aqueous chemical environment. Both of these factors greatly influence osteoblast migration, cytoskeletal organization, and calcium nodule production, important aspects when considering the biocompatibility of bone implants. By perturbing the physical and/or chemical micro-environment, it may be possible to elucidate effects on cellular function. To examine these factors, murine pre-osteoblasts (MC3T3-E1 subclones 4 and 24) were seeded on polydimethylsiloxane (PDMS) substrates containing "wide" micro-patterned ridges (20 mum width, 30 mum pitch, & 2 mum height), "narrow" micro-patterned ridges (2 mum width, 10 mum pitch, 2 mum height), no patterns (flat PDMS), and standard tissue culture (TC) polystyrene as a control. Zinc concentration was adjusted to mimic deficient (0.23 muM), serum-level (3.6 muM), and zinc-rich (50 muM) conditions. It was found that cells exhibited distinct anisotropic migration in serum-level zinc and zinc-deficient media on the wide PDMS patterns, however this was disrupted under zinc-rich conditions. Production of differentiation effectors, activated metalloproteinase-2 (MMP-2) and transforming growth factor - beta 1 (TGF-beta1), was increased with the addition of exogenous zinc. Early stage differentiation, via alkaline phosphatase, was modified by zinc levels on patterned polydimethylsiloxane (PDMS) surfaces, but not on flat PDMS or tissue culture polystyrene (TC). Late stage differentiation, visualized through calcium phosphate nodules, was markedly different at various zinc levels when the cells were cultured on TC substrates. This susceptibility to zinc content can lead to differences in bone mineral production on certain substrates if osteoblasts are not able to maintain and remodel bone effectively, a process vital to successful biomaterial integration.