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In this report, we present an inverse opal scaffold that can enhance the chondrogenic differentiation of human adipose-derived stem cells (hADSCs) without drug, gene, or cytokine supplement. Inverse opal scaffolds based on poly(D,L-lactide-co-glycolide) were formed with uniform 200 µm pores. Due to uniform pore sizes and well-con- trolled interconnectivity of inverse opal scaffold, hADSCs were allowed to distribute homogeneously throughout the scaffolds. As a result, high cell density culture with scaffold was possible. Since the hADSCs cultured in inverse opal scaffolds were subjected to limited supplies of oxygen and nutrients, these cells were naturally preconditioned to a hypoxic environment that stimulated the up-regulation of hypoxia-inducible factor-1α (HIF-1α). As a result, apoptotic activity of hADSCs until 3 weeks after initial cell seeding was significantly reduced and chondrogenic differentiation related molecular signal cascades were up regulated (transforming growth factor-beta, phosphorylated AKT, and phos- phorylated p38 expression). In contrast, hADSCs cultured with small and non-uniform porous scaffolds showed signif- icantly increased apoptotic activity with decreased chondrogenic differentiation. Taken together, inverse opal scaffold could potentially be used as an effective tool for improving chondrogenesis using stem cells.

Enhanced Chondrogenic Differentiation of Human Adipose-derived Stem Cells with Inverse Opal Scaffolds