Bioinspired mineralization of engineered living materials to promote osteogenic differentiation

Parra-Torrejón, B., Jayawarna, V., Rodrigo-Navarro, A. , Gonzalez, J., Dobre, O. , Ramírez-Rodríguez, G. B., Salmeron-Sanchez, M. and Delgado-López, J. M. (2023) Bioinspired mineralization of engineered living materials to promote osteogenic differentiation. Biomaterials Advances, 154, 213587. (doi: 10.1016/j.bioadv.2023.213587) (PMID:37633007)

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Abstract

In this work, Engineered Living Materials (ELMs), based on the combination of genetically-modified bacteria and mineral-reinforced organic matrices, and endowed with self-healing or regenerative properties and adaptation to specific biological environments were developed. Concretely, we produced ELMs combining human mesenchymal stem cells (hMSCs) and Lactococcus lactis, which was specifically programmed to deliver bone morphogenetic protein (BMP-2) upon external stimulation using nisin, into mineralized alginate matrices. The hybrid organic/inorganic matrix was built through a protocol, inspired by bone mineralization, in which alginate (Alg) assembly and apatite (HA) mineralization occurred simultaneously driven by calcium ions. Chemical composition, structure and reologhical properties of the hybrid 3D matrices were dedicately optimized prior the incorportation of the living entities. Then, the same protocol was reproduced in the presence of hMSC and engineered L. lactis that secrete BMP-2 resulting in 3D hybrid living hydrogels. hMSC viability and osteogenic differentiation in the absence and presence of the bacteria were evaluated by live/dead and quantitative real-time polymerase chain reaction (qPCR) and immunofluorescence assays, respectively. Results demonstrate that these 3D engineered living material support osteogenic differentiation of hMSCs due to the synergistic effect between HA and the growth factors BMP-2 delivered by L. lactis.

Item Type:Articles
Additional Information:This study was supported by EPSRC (EP/P001114/1) and a grant from the U.K. Regenerative Medicine Platform “Acellular/Smart Materials-3D Architecture” (MR/R015651/1), Junta de Andalucía through the collaborative project NanoFERTI (P18-TP-0969) and the Spanish MCIN/AEI/10.13039/501100011033 and by the “European Union” NextGenerationEU/PRTR (project number PDC2022-133191-I00). BPT and GBRR acknowledge the funding from the EMBO Scientific Exchange Grant (SEG number 9741) and RYC2021-032734-I funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”, respectively.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Rodrigo-Navarro, Mr Aleixandre and Dobre, Dr Oana and Jayawarna, Dr Vineetha and Gonzalez, Dr Juan
Authors: Parra-Torrejón, B., Jayawarna, V., Rodrigo-Navarro, A., Gonzalez, J., Dobre, O., Ramírez-Rodríguez, G. B., Salmeron-Sanchez, M., and Delgado-López, J. M.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Biomaterials Advances
Publisher:Elsevier
ISSN:2772-9516
ISSN (Online):2772-9508
Published Online:14 August 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Biomaterials Advances 154:213587
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173192Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - Biomedical Engineering
301095UKRMP2 Acellular/Smart Materials 3D Architecture HubManuel Salmeron-SanchezMedical Research Council (MRC)MMRE_P75176 (MR/R015651/1ENG - Biomedical Engineering