Sustained localized presentation of RNA interfering molecules from in situ forming hydrogels to guide stem cell osteogenic differentiation.
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.
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44016, USA.
Minh K
MK
Nguyen
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44016, USA.
Oju
O
Jeon
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44016, USA.|Chemical and Biological Engineering Department, Colorado School of Mines, 1500 Illinois Street, Golden, Colorado 80401, USA.
Melissa D
MD
Krebs
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44016, USA.
Daniel
D
Schapira
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44016, USA.|Department of Orthopeadic Surgery, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44016, USA.
Eben
E
Alsberg
D000469:Alkaline Phosphatase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012212:Rheology; D013997:Time Factors
D020100:Hydrogels; D034741:RNA, Small Interfering; D000469:Alkaline Phosphatase; D002118:Calcium
Biomaterials; Bone regeneration; Gene delivery; Mesenchymal stem cells; Tissue engineering