Diatom silica frustules-doped fibers for controlled release of melatonin for bone regeneration

Abstract

Sustained release of a bioactive agent from a tissue engineering scaffold is one of the most common strategies to improve regenerative potential of the construct. However, depending on the chemistry of the agent, achieving high enough loading and controlled release can be challenging depending on the scaffold materials. These shortcomings can be solved by novel scaffold design fabricated by appropriate techniques and materials for the target tissue. In this study, an electrospun scaffold was designed to improve osteogenic activity of cells and diatom silica frustules were used to sustain loading and controlled release of a hydrophilic molecule, melatonin. Fibrous scaffolds were produced via wet electrospinning of the polymer blend solution poly(hydroxybutyrate-co- hydroxyvalerate (PHBV)/poly(epsilon-caprolactone) (PCL) which contains melatonin loaded diatom frustules. In the 3D fiber matrix diatom frustules were covered with a polymer coat which successfully lowered melatonin release more than half through 7 days achieving a controlled release. Melatonin had a concentration dependent effect on ALP activity of cells, while scaffolds bearing melatonin loaded frustules have significantly improved ALP activity of Saos-2 cells. Developed scaffold system has successfully induced osteogenic activity by controlled melatonin delivery and silica nature of diatom frustules which hold potential use for bone tissue engineering.