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RANKL release from self-assembling nanofiber hydrogels for inducing osteoclastogenesis in vitro
James Z Xing1, Lei Lu2, Larry D Unsworth2
1School of Dentistry, University of Alberta, Edmonton, Alberta T6G 1C9, Canada; Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
Acta Biomaterialia
|December 13, 2016
Summary
This study developed a nanofiber hydrogel (NF-hydrogel) for sustained release of receptor activator of NF-kB ligand (RANKL). The NF-hydrogel effectively delivered bioactive RANKL for potential orthodontic applications, demonstrating controlled osteoclastogenesis.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Orthodontics
Background:
- Orthodontic tooth movement (OTM) relies on controlled bone remodeling regulated by RANKL.
- Systemic RANKL administration for accelerated OTM poses risks of skeletal bone loss.
- Local, controlled RANKL delivery is needed to maximize therapeutic benefits and minimize side effects.
Purpose of the Study:
- To develop a nanofiber hydrogel (NF-hydrogel) for sustained and controlled release of RANKL.
- To characterize the release kinetics and bioactivity of RANKL delivered via NF-hydrogel.
Main Methods:
- Fluorescently-labeled RANKL was incorporated into varying concentrations of NF-hydrogels.
- In vitro release rates were measured, and nano-structures were analyzed by AFM.
- Released RANKL structure was assessed using CD and fluorescent emission spectroscopy.
- Bioactivity was confirmed by NFATc1 gene expression and TRAP activity in osteoclasts.
Main Results:
- NF-hydrogel concentration (0.5-2%) dictated sustained RANKL release up to 48h.
- 2% NF-hydrogel showed slow, sustained RANKL release.
- Released RANKL retained its native structure and bioactivity, confirmed by gene expression and enzyme activity.
Conclusions:
- The self-assembling NF-hydrogel system enables sustained, local RANKL release.
- This controlled delivery can induce osteoclastogenesis for orthodontic tooth movement.
- Results support further in vivo investigation of NF-hydrogel RANKL delivery systems.
