Sustained localized presentation of RNA interfering molecules from in situ forming hydrogels to guide stem cell osteogenic differentiation

Abstract To date, RNA interfering molecules have been used to differentiate stem cells on two-dimensional (2D) substrates that do not mimic three-dimensional (3D) microenvironments in the body. Here, in situ forming poly(ethylene glycol) (PEG) hydrogels were engineered for controlled, localized and...

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Bibliographic Details
Published in:Biomaterials 2014-08, Vol.35 (24), p.6278-6286
Main Authors: Nguyen, Minh K, Jeon, Oju, Krebs, Melissa D, Schapira, Daniel, Alsberg, Eben
Format: Article
Language:English
Subjects:
Advanced Basic Science
Alkaline Phosphatase - metabolism
bioactive properties
Biomaterials
bone formation
Bone regeneration
Calcium - metabolism
Cell Differentiation
Dentistry
encapsulation
Gene delivery
Humans
hydrogels
Hydrogels - chemical synthesis
Hydrogels - chemistry
Kinetics
Magnetic Resonance Spectroscopy
medicine
Mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - drug effects
Mesenchymal Stromal Cells - metabolism
microRNA
Osteogenesis
polyethylene glycol
Rheology
RNA Interference
RNA, Small Interfering - metabolism
small interfering RNA
stem cells
Time Factors
Tissue engineering
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Summary:Abstract To date, RNA interfering molecules have been used to differentiate stem cells on two-dimensional (2D) substrates that do not mimic three-dimensional (3D) microenvironments in the body. Here, in situ forming poly(ethylene glycol) (PEG) hydrogels were engineered for controlled, localized and sustained delivery of RNA interfering molecules to differentiate stem cells encapsulated within the 3D polymer network. RNA interfering molecules were released from the hydrogels in a sustained and controlled manner over the course of 3–6 weeks, and exhibited high bioactivity. Importantly, it was demonstrated that the delivery of siRNA and/or miRNA from the hydrogel constructs enhanced the osteogenic differentiation of encapsulated stem cells. Prolonged delivery of siRNA and/or miRNA from this polymeric scaffold permitted extended regulation of cell behavior, unlike traditional siRNA experiments performed in vitro . This approach presents a powerful new methodology for controlling cell fate, and is promising for multiple applications in tissue engineering and regenerative medicine.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2014.04.048