In vivo functionalization of diatom biosilica with sodium alendronate as osteoactive material

Bisphosphonates are a class of drugs widely used in the clinical treatment of disorders of bone metabolism, such as osteoporosis, fibrous dysplasia, myeloma and bone metastases. Because of the negative side effects caused by oral administration of bisphosphonates, various silica mesoporous materials have been investigated for a confined and controlled release of these drugs. Here, we propose biosilica from diatoms as suitable substrate for alendronate local activation of bone cells. Following a novel strategy, sodium alendronate can be in vivo incorporated into biosilica shells of cultured Thalassiosira weissflogii diatoms, by feeding the algae with an aqueous solution of the drug. After acid/oxidative treatments for removing organic matter, the resulting bisphosphonate-functionalized mesoporous biosilica was characterized and tested as osteoinductive support. Effects on osteoblast growth and anti-osteoclast activity have been examined by evaluating SaOS-2, BMSC, J774 cell viability on the alendronate-"doped" biosilica. The loading percentage of sodium alendronate into biosilica, estimated as 1.45% w/w via TGA, was able to decrease metabolic activity of J774 osteoclasts-like cells till 5% over glass control. We demonstrated a good osteoconductive ability and activation of a tissue regeneration model together with osteoclasts inhibition of the functionalized biosilica, opening the way to interesting applications for diatom microalgae as a bioinspired mesoporous material for tissue engineering.