Continuous functionally graded materials (cFGMs) for TE

Biological structures are not uniform but possess spatially distributed functions and properties, or functional gradients. To ensure functional, mechanical and structural integration, a tissue engineered (TE) scaffold has to reproduce these functional gradients. However the fabrication of functionally graded materials is challenging and usually an experimental trial-and-error approach is used. In this work we present a controlled method for the fabrication of cFGMs using the gravitational sedimentation of discrete solid particles within a primary fluid phase. To have an overall control over particle distribution, a time-varying dynamic viscosity solution (i.e. thermo-sensitive) was used as fluid phase. Computational fluid dynamic models were developed to have a fine control over particle distribution. Biomimetic osteochondral cFGMs scaffolds were fabricated using hydroxyapatite (HA) and gelatin. Glutaraldehyde was used to covalently bind gelatin-HA graded scaffolds. Mechanical properties were measured and correlated as a function of HA volume fraction. SEM-EDX analysis was used to further characterise HA content and its distribution within gelatin-HA cFGMs. Finally gelatin-HA cFGMs scaffold were seeded using periosteum derived progenitor cells, to investigate how the HA gradient modulates cell response. This approach represents an innovative yet simple tool for the fabrication of tailored cFGMs with biologically and physiologically relevant gradients for TE applications.