Martínez Ledo, AdrianaSenra, AnaRilo Álvarez, HéctorBorrajo Alonso, EreaVidal Figueroa, AnxoAlonso Fernández, María JoséGarcía Fuentes, Marcos2020-07-312022-03-312020Ledo, A. M., Senra, A., Rilo-Alvarez, H., Borrajo, E., Vidal, A., Alonso, M. J., & Garcia-Fuentes, M. (2020). mRNA-activated matrices encoding transcription factors as primers of cell differentiation in tissue engineering. Biomaterials, 247, 120016-120016.0142-9612http://hdl.handle.net/10347/23240Gene-activated matrices (GAMs) encoding pivotal transcription factors (TFs) represent a powerful tool to direct stem cell specification for tissue engineering applications. However, current TF-based GAMs activated with pDNA, are challenged by their low transfection efficiency and delayed transgene expression. Here, we report a GAM technology activated with mRNAs encoding TFs SOX9 (cartilage) and MYOD (muscle). We find that these mRNA-GAMs induce a higher and faster TF expression compared to pDNA-GAMs, especially in the case of RNase resistant mRNA sequences. This potent TF expression was translated into a high synthesis of cartilage- and muscle-specific markers, and ultimately, into successful tissue specification in vitro. Additionally, we show that the expression of tissue-specific markers can be further modulated by altering the properties of the mRNA-GAM environment. These results highlight the value of this GAM technology for priming cell lineage specification, a key centerpiece for future tissue engineering devices.eng© 2020 Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (http://creativecommons.org/licenses/by-nc-nd/4.0/)http://creativecommons.org/licenses/by-nc-nd/4.0/http://creativecommons.org/licenses/by-nc-nd/4.0/GAMs3D transfectionmRNATranscription factorsLineage primingTissue engineeringjournal article10.1016/j.biomaterials.2020.120016open access