Hierarchical assembly of nanostructured coating for siRNA-based dual therapy of bone regeneration and revascularization. (March 2020)

• Record Type: Journal Article
• Authors: Xing, Helin; Wang, Xing; Xiao, Gao; Zhao, Zongmin; Zou, Shiquan; Li, Man; Richardson, Joseph J.; Tardy, Blaise L.; Xie, Liangxia; Komasa, Satoshi; Okazaki, Joji; Jiang, Qingsong; Yang, Guodong; Guo, Junling
• Is Part Of: Biomaterials. Volume 235(2020)
• Publication Date: 2020-03
• Subjects: Colloidal assembly -- Surface functionalization -- siRNA -- Revascularization -- Bone regeneration; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2020.119784
• Languages: English
• ISSNs: 0142-9612

Abstract

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. Graphical abstract: siRNA-decorated nanoparticles were assembled to engineer a hierarchical nanostructured coating on clinically used titanium implants for the synergistic regeneration of skeletal and vascular tissues. The release of siRNA targeted the regulation of cathepsin K and enhanced bone-implant interfacial interaction. siRNA- CTSK could be released and internalized by the adjacent macrophages, demonstrating a therapeutic improvement on the osteointegration with synergetic effects on bone regeneration and blood vessel system repair in vitro and in vivo . The use of multi-scaled bio-functional coatings as presented herein may find applications in regenerative medicine for other tissue due to their ability to favor complex stem cell differentiation paths. Image 1