The alluring correlations of cellular behaviors with
viscoelastic
extracellular matrices have driven increasing endeavors directed toward
the understanding of mechanical cues on cell growth and differentiation
via preparing biomimetic scaffolds/gels with viscoelastic controllability.
Indeed, systematic investigations, especially into calcium phosphate-containing
biomimetics, are relatively rare. Here, oxidized hyaluronic acid/hydroxyapatite
hybrids (OHAHs) were synthesized by hyaluronan-mediated biomimetic
mineralization with confined ion diffusion and subsequent oxidization
treatment. The collagen self-assembly was applied to fabricate tunable
stress relaxing fibrillar matrices in the presence of OHAHs in which
the incorporated hyaluronic acid with aldehyde groups acted to improve
the component compatibility as well as to supplement the molecular
interactions with the occurrence of a Schiff-base reaction. With the
addition of varying OHAH contents, the self-assembly behavior of collagen
was altered, and the obtained collagen-hybrid (CH) matrices presented
a heterogeneous fibrillar structure interspersed with OHAHs, characterized
by large fibrillar bundles coexisting with small fibrils. The OHAHs
improved the hydrogel stability of pure collagen, and according to
rheological and nanoindentation measurements, CH matrices also exhibited
tunable stress relaxation rates, following an OHAH concentration-dependent
fashion. The proliferation and spreading of MC3T3-E1 cells cultured
onto such CH matrices were further found to increase with the stress
relaxing rate of the matrices. The present study showed that the introduction
of hydroxyapatite incorporated with active hyaluronic acid during
collagen reconstitution was a simple and effective strategy to realize
the preparation of tunable stress relaxing biomimetic matrices potentially
used for further appraising the regulation of mechanical cues on cell
behaviors.