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

doi:10.1016/j.biomaterials.2020.119784

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

Biomaterials. 2020 Mar:235:119784. doi: 10.1016/j.biomaterials.2020.119784. Epub 2020 Jan 14.

Authors

Helin Xing¹, Xing Wang², Gao Xiao³, Zongmin Zhao⁴, Shiquan Zou¹, Man Li¹, Joseph J Richardson⁵, Blaise L Tardy⁶, Liangxia Xie⁷, Satoshi Komasa⁸, Joji Okazaki⁸, Qingsong Jiang⁹, Guodong Yang¹⁰, Junling Guo¹¹

Affiliations

¹ Department of Prosthodontics, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, 100050, China.
² Hospital of Stomatology, Shanxi Medical University, Taiyuan, 030001, China.
³ School of Biomass Science and Engineering, Sichuan University, Chengdu, 610065, China; Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, 02115, United States.
⁴ Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, 02115, United States.
⁵ ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria, 3010, Australia.
⁶ Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, P. O. Box 16300, 00076, Finland.
⁷ Department of Pathology, Brigham and Women's Hospital, Harvard University, Boston, MA, 02115, United States.
⁸ Department of Removable Prosthodontics and Occlusion, Osaka Dental University, Hirakata, Osaka, 540-8570, Japan.
⁹ Department of Prosthodontics, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, 100050, China. Electronic address: qsjiang@ccmu.edu.cn.
¹⁰ The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, 710032, China. Electronic address: yanggd@fmmu.edu.cn.
¹¹ School of Biomass Science and Engineering, Sichuan University, Chengdu, 610065, China; Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, 02115, United States. Electronic address: junling.guo@scu.edu.cn.

PMID: 31981763
DOI: 10.1016/j.biomaterials.2020.119784

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.

Keywords: Bone regeneration; Colloidal assembly; Revascularization; Surface functionalization; siRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Regeneration
Coated Materials, Biocompatible*
Dogs
Nanostructures*
RNA, Small Interfering
Rats
Surface Properties
Titanium

Substances

Coated Materials, Biocompatible
RNA, Small Interfering
Titanium