@article {18058, title = {A combinatorial study of nanocomposite hydrogels: on-chip mechanical/viscoelastic and pre-osteoblast interaction characterization}, journal = {Journal of Materials Chemistry B}, year = {2014}, month = {2014-07-24 00:00:00}, abstract = {

Nanocomposite hydrogels were prepared in a combinatorial way with chitosan, bioglass nanoparticles
(BG-NPs) and distinct amounts of crosslinker (genipin), in a total of 30 formulations. Such miniaturized
hydrogels were prepared by dispensing the precursor solutions in wettable spots previously patterned
onto superhydrophobic surfaces. The chips were used as platforms to analyze the biomaterials on-chip
both for mechanical/viscoelastic and cell{\textendash}biomaterial interactions. We adapted a mechanical dynamic
analyzer (DMA) in order to perform the in situ totally unconfined solid-state rheological characterization
of biomaterials under physiological-like conditions. We concluded that the viscoelastic properties of the
hydrogels are dependent on the three factors studied. Besides influencing biomaterials{\textquoteright} mechanical
properties, bioglass fillers also confer bioactivity. We immersed the chips with 20 distinct biomaterial
formulations in a cell suspension of MC3T3-E1 pre-osteoblasts and quantified {\textendash} using image analysis
compatible with the maintenance of the integrity of the chip {\textendash} selective cell adhesion after 1 day of cell
culture, as well as cell proliferation and cell morphology at day 3. Linear regression studies showed that
for the range of conditions studied herein, neither cell adhesion nor proliferation depended directly on
the biomaterials{\textquoteright} mechanical/viscoelastic properties. Rather, cell proliferation was favoured in the
presence of an intermediate amount of BGNPs (12.5\% w/w) for all chitosan/genipin conditions, especially
in softer hydrogels (2\% (w/v) chitosan, 2.5\% (w/w) genipin). This hit-spotted condition also favoured cell
spreading. Interestingly, the elastic modulus measured for this formulation meets the values reported for
the granulation tissue occurring during bone regeneration, where fibroblasts produce collagen. We
believe that this approach will facilitate the complete on-chip rapid study of miniaturized biomaterials, in
order to get more adequate formulations to be used in tissue engineering or other biomedical applications.

}, keywords = {combinatorial, high-throughput, superhydrophobic surfaces}, doi = {10.1039/C4TB00437J}, url = {http://pubs.rsc.org/en/content/articlepdf/2014/tb/c4tb00437j?page=search}, author = {Oliveira, M.B. and Luz, G. M. and Mano, J. F.} }