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

Helin Xing, Xing Wang, Gao Xiao, Zongmin Zhao, Shiquan Zou, Man Li, Joseph J. Richardson, Blaise L. Tardy, Liangxia Xie, Satoshi Komasa, Joji Okazaki, Qingsong Jiang, Guodong Yang, Junling Guo*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number119784
JournalBiomaterials
Volume235
DOIs
Publication statusPublished - 1 Mar 2020
MoE publication typeA1 Journal article-refereed

Keywords

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

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    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, 235, [119784]. https://doi.org/10.1016/j.biomaterials.2020.119784