Sustained localized presentation of RNA interfering molecules from in situ forming hydrogels to guide stem cell osteogenic differentiation |
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Authors: | Minh K Nguyen Oju Jeon Melissa D Krebs Daniel Schapira Eben Alsberg |
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Institution: | 1. Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44016, USA;2. Department of Orthopaedic Surgery, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44016, USA;3. National Center for Regenerative Medicine, Division of General Medical Sciences, Case Western Reserve University, Cleveland, OH, USA |
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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. |
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Keywords: | Biomaterials Mesenchymal stem cells Tissue engineering Gene delivery Bone regeneration |
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