Free and copolymerized gamma-cyclodextrins regulate performance of dexamethasone-loaded dextran microspheres for bone regeneration

Polymeric particles acting as source of biological cues to promote tissue regeneration are currently an interesting topic in bone tissue engineering research. In this study, microspheres of dextran-methacrylated (dextran-MA) and γ-cyclodextrins (γ-CD) for the delivery of osteogenic agents were prepared by means of photopolymerization on biomimetic superhydrophobic surfaces. The effects of the incorporation of the γ-CD units as free entities or as structural monomers (acrylamidomethyl-γ-cyclodextrin, γ-CD-NMA) on dexamethasone loading and release performance were evaluated in detail in order to achieve osteogenic differentiation of human stem cells. The copolymerization of dextran-MA with γ-CD-NMA improved the loading capacity of the particles and also provided a sustained release of dexamethasone for several days. The biological studies revealed that such microspheres were cytocompatible and capable to induce the differentiation of human adipose-derived stem cells (hASCs) to osteoblasts, as determined from an increase of alkaline phosphatase (ALP) activity between days 3 and 7. Such results were also confirmed using ALP staining. Therefore, immobilization of γ-CDs onto dextran-MA network may be particularly useful for the development of cytocompatible implantable spherical biomaterials for bone tissue engineering purposes.