Glypican-based drug releasing titania implants to regulate BMP2 bioactivity as a potential approach for craniosynostosis therapy

Advances in molecular biology and nanomedicine based therapies hold promise to obviate the need of multiple surgical interventions (associated with current management) in craniosynostosis by preventing bone re-ossification. One such adjunctive therapy involves application of glypicans 1 and 3 (GPC1 and GPC3) that are BMP inhibitors implicated in downregulating the BMP2 activity in prematurely fusing sutures. Electrochemically anodized Titania nanotube (TNT) arrays have been recognized as a promising localized, long-term drug delivery platform for bone-related therapies. This study presents the application of nanoengineered TNT/Ti implants loaded with recombinant glypicans for craniosynostosis therapy. By using Dual luciferase Reporter assay, we tested the biofunctionality of eluted glypicans from the TNT/Ti implants for BMP2 bioactivity regulation in C2C12 murine myoblast cell line. BMP2 activity was inhibited significantly for up to 15days by the glypicans released from polymer-coated TNT/Ti implants, indicating their potential application in adjunctive craniosynostosis treatment. Titania nanotube- based protein delivery implants have been assessed in vitro to provide a sustained release of bone inhibiting glypicans (rGPC1 and rGPC3). The bioactivity of released glypicans was confirmed by downregulation of BMP2 expression in transfected C2C12 cells. [Display omitted] •Titania nanotubes (TNTs) implants have been engineered by electrochemical process.•TNTs glypican releasing implants have been prepared and evaluated.•BMP2 activity was inhibited significantly for up to 15days by these implants.•The potential for craniosynostosis therapy is proposed by this approach.