Minh K Nguyen1, Oju Jeon1, Melissa D Krebs1,2, Daniel Schapira1, Eben Alsberg1,3. 1. Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44016, USA. 2. Chemical and Biological Engineering Department, Colorado School of Mines, 1500 Illinois Street, Golden, Colorado 80401, USA. 3. Department of Orthopeadic Surgery, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44016, USA.
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.
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 pan class="Chemical">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.
Authors: Gajadhar Bhakta; Bina Rai; Zophia X H Lim; James H Hui; Gary S Stein; Andre J van Wijnen; Victor Nurcombe; Glenn D Prestwich; Simon M Cool Journal: Biomaterials Date: 2012-06-09 Impact factor: 12.479
Authors: Ahmed Fawzy Ibrahim; Ulrike Weirauch; Maren Thomas; Arnold Grünweller; Roland K Hartmann; Achim Aigner Journal: Cancer Res Date: 2011-06-20 Impact factor: 12.701
Authors: Michelle F Griffin; Peter E Butler; Alexander M Seifalian; Deepak M Kalaskar Journal: World J Stem Cells Date: 2015-01-26 Impact factor: 5.326
Authors: Siddharth Patel; Avathamsa Athirasala; Paula P Menezes; N Ashwanikumar; Ting Zou; Gaurav Sahay; Luiz E Bertassoni Journal: Tissue Eng Part A Date: 2018-06-07 Impact factor: 3.845