(579a) Novel Inorganic-Organic Hybrid Hydrogels for Bone Tissue Engineering

            Millions
suffer from often debilitating bone injuries and diseases each year. Often,
defects remain which must be treated to restore original function to the bone.
Development of tissue engineering as a bone regeneration option requires
identification of a suitable osteoconductive matrix. Hydrophobic scaffolds such
as poly(propylene fumarates) and polyanhydrides  have shown promise as
osteoconductive matrices, and recently, hydrophilic polyethylene oxide (PEO) hydrogels
to which cell adhesion ligands have been conjugated were demonstrated to
provide an osteoconductive environment. Based on these results, scaffolds in
which the level of hydrophobicity can be tuned may be particularly desirable
for optimizing the formulation of bone tissue engineering matrices.

            In
the present study, we characterize the effects of novel inorganic-organic hydrogel
scaffolds generated by the photo-cure of star polydimethylsiloxane (PDMS_star)
(hydrophobic inorganic polymer) and linear hydrophilic PEO on rat osteoblast extracellular
matrix (ECM) production, alkaline phosphatase expression, and calcium
deposition. Initial studies have shown these hybrid scaffolds to display a
range of hydrophobicities as well as microstructural, biochemical, and
biomechanical properties that can be precisely tuned over a broad range.

            By
varying the ratio of PDMS_star to PEO, the modulus of the hydrogels
remained constant. However, gradual alterations in hydrophobicity and microscale
scaffold morphology were introduced. These alterations in morphology impacted
cellular ECM production and calcium deposition. Specifically, cells demonstrated
a moderate increase in collagen type I, osteocalcein, and alkaline phosphatase as
hydrophobic PDMS_star levels increased from 0 to 1%. However,
production of these same markers fell dramatically as hydrophobicity increased
beyond this point. Similarly, the levels of collagen and GAG production varied
significantly with hydrogel PDMS_star concentration. Thus, by
modifying the composition of novel inorganic-organic PDMS_star:PEO
hydrogels, we are able to modulate the ECM production and differentiation of encapsulated
rat osteoblasts. Future investigation of the impact of systematic alterations
in the microstructural, biochemical, and biomechanical properties of these
hybrid scaffolds on cell behavior should therefore yield profound insight into
the dependence of cell behavior on material properties.