Bone-Like Mineral and Organically Modified Bone-Like Mineral Coatings - Biological and Biomedical Coatings: Processing and Characterization - page 7

by electron beam lithography on polymethylmethacrylate (PMMA). Cells grown on these
nanostructures engaged in osteogenic differentiation and bone mineral formation with-
out the addition of osteogenic factors to the culture media (Dalby et al. 2007; Dalby et al.
2004).
Substrate elasticity. Substrate elasticity also plays an important role in cell adhesion, pro-
liferation, and differentiation, thereby enhancing osteoconduction and osseointegration.
Advances in materials engineering offer a variety of polymer substrates with elasticities
that may be tuned to match the stiffness of specific tissues (Thompson et al. 2005; Kloxin,
Benton, and Anseth 2010; Lo et al. 2000; Discher, Mooney, and Zandstra 2009). These tun-
able polymers are used to observe effects of substrate compliance on adhesion and prolif-
eration independent of surface chemistry and topographical effects.
A variety of cells, including fibroblasts, epithelial cells, myocytes, and osteoblasts, show
increased adhesion and proliferation on stiffer substrates (Mitragotri and Lahann 2009;
Griffin et al. 2004). For example, kidney epithelial cells grown on polyelectrolyte multi-
layers show increased adhesion with increasing modulus between 50 and 500 kPa (Kocgozlu
et al. 2010). Mesenchymal cells show markers for neurogenic, myogenic, and osteogenic
differentiation when cultured on polyacrylamide gels with stiffness analogous to native
brain, muscle, and osteoid, respectively (Engler et al. 2006). Therefore, material stiffness
can be a useful parameter to direct osteoconduction and osseointegration. However, it is
important to consider the integrated roles of surface chemistry, surface topography, and
elasticity to amplify osteoconductive effects of a biomaterial surface.
One way to incorporate the desired surface properties into an implant or scaffolding
material is to use coating techniques wherein the chemistry of the coatings can be con-
trolled to provide the required roughness, elasticity, and crystallinity. Hydroxyapatite coat-
ings are the most commonly used inorganic coatings on bone implants and in regenerative
therapies, and can be used to increase modify the microtopography of substrate surfaces.
Hydroxyapatite coatings with surface roughness ( R a ) values in the range of 0.7-4.8 show
significantly increased human bone marrow stromal cell adhesion and proliferation with
increasing R a (Deligianni et al. 2001).
HA coatings with low crystallinity show increased dissolution compared to highly crys-
talline coatings (Lee et al. 2009). In addition to varying crystallinity, crystallite size can
also be varied by altering processing temperatures. Coatings with larger crystallite size
exhibit lower dissolution and improved stability of the crystallographic lattice (Zhang et
al. 2003).
In addition to affording control over dissolution and surface roughness, crystallinity is
reported to improve osseointegration. For example, fibroblasts cultured on 98% crystalline
HA coatings exhibit enhanced adhesion and proliferation compared to 65% crystalline,
25% crystalline, and uncoated titanium surfaces after 14 days of culture (Chou, Marek,
and Wagner 1999). In vivo, canine femoral implants having 98% crystalline HA coatings
showed greater integration with surrounding bone 3 months postimplantation compared
to implants with 50% crystalline HA coatings (Xue et al. 2004).
However, other studies show no significant increase in osseointegration with changes
in crystallinity. For example, no difference in bone formation was observed between 50%,
70%, and 90% crystalline coatings at 4, 12, and 24 weeks (Lacefield 1999). Similar studies
using 100% and 40% crystalline HA coatings also resulted in no discernable difference in
osseointegration (Frayssinet et al. 1994). Further research is required to more thoroughly
elucidate the role of crystallinity in osseointegration. Although crystallinity maintains the
osteoconductive properties of a material while providing control over coating delamina-
tion (Lacefield 1999), an osteoconductive material is not always osseointegrative. Therefore,