Hierarchical assembly of nanostructured coating for siRNA-based dual therapy of bone regeneration and revascularization

Advancing bone implant engineering offers the opportunity to overcome crucial medical challenges and improve clinical outcomes. Although the establishment of a functional vascular network is crucial for bone development, its regeneration inside bone tissue has only received limited attention to date. Herein, we utilize siRNA-decorated particles to engineer a hierarchical nanostructured coating on clinically used titanium implants for the synergistic regeneration of skeletal and vascular tissues. Specifically, an siRNA was designed to target the regulation of cathepsin K and conjugated on nanoparticles. The functionalized nanoparticles were assembled onto the bone implant to form a hierarchical nanostructured coating. By regulating mRNA transcription, the coating significantly promotes cell viability and growth factor release related to vascularization. Moreover, microchip-based experiments demonstrate that the nanostructured coating facilitates macrophage-induced synergy in up-regulation of at least seven bone and vascular growth factors. Ovariectomized rat and comprehensive beagle dog models highlight that this siRNA-integrated nanostructured coating possesses all the key traits of a clinically promising candidate to address the myriad of challenges associated with bone regeneration.

Keywords

Bone regeneration, Colloidal assembly, Revascularization, siRNA, Surface functionalization

DOI

10.1016/j.biomaterials.2020.119784

Citation

Xing, H, Wang, X, Xiao, G, Zhao, Z, Zou, S, Li, M, Richardson, J J, Tardy, B L, Xie, L, Komasa, S, Okazaki, J, Jiang, Q, Yang, G & Guo, J 2020, ' Hierarchical assembly of nanostructured coating for siRNA-based dual therapy of bone regeneration and revascularization ', Biomaterials, vol. 235, 119784 . https://doi.org/10.1016/j.biomaterials.2020.119784

Permanent link to this item

https://urn.fi/URN:NBN:fi:aalto-202002122211

Collections

[article-cris] Kemian tekniikan korkeakoulu / CHEM

Show all metadata