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Incorporation of resident macrophages in engineered tissues: Multiple cell type response to microenvironment controlled macrophage-laden gelatine hydrogels

Dollinger, Camille; Ciftci, Sait; Knopf-Marques, Helena; Ghaemmaghami, Amir M.; Debry, Christian; Barthes, Julien; Vrana, Nihal Engin

Authors

Camille Dollinger

Sait Ciftci

Helena Knopf-Marques helenamarque@gmail.com

Christian Debry

Julien Barthes

Nihal Engin Vrana



Abstract

The success of tissue engineering strategy is strongly related to the inflammatory response, mainly through the activity of macrophages that are key cells in initial immune response to implants. For engineered tissues, the presence of resident macrophages can be beneficial for maintenance of homeostasis and healing. Thus, incorporation of macrophages in engineered tissues can facilitate the integration upon implantation. In this study, we developed an in-vitro model of interaction between encapsulated naive monocytes, macrophages induced with M1/M2 stimulation and incoming cells for immune assisted tissue engineering applications. To mimic the wound healing cascade, Naive THP-1 monocytes, endothelial cells, and fibroblasts were seeded on the gels as incoming cells. The interaction was first monitored in the absence of the gels. In order to mimic resident macrophages, THP-1 cells were encapsulated in the presence or absence of IL-4 to control their phenotype and then these hydrogels were seeded with incoming cells. Without encapsulation, activated macrophages induce apoptosis in endothelial cells. Once encapsulated no adverse effects were seen. Macrophage-laden hydrogels attracted more endothelial cells and fibroblasts compared to monocytes-laden hydrogels. The induction (M2 stimulation) of encapsulated macrophages did not change the overall number of attracted cells; but significantly affected their morphology. M1 stimulation by a defined media resulted in secretion of both pro and anti-inflammatory cytokines compared to M2 stimulation. We demonstrated that there is a distinct effect of encapsulated macrophages on the behavior of the incoming cells; this effect can be harnessed to establish a microenvironment more prone to regeneration upon implantation.

Citation

Dollinger, C., Ciftci, S., Knopf-Marques, H., Ghaemmaghami, A. M., Debry, C., Barthes, J., & Vrana, N. E. (2018). Incorporation of resident macrophages in engineered tissues: Multiple cell type response to microenvironment controlled macrophage-laden gelatine hydrogels. Journal of Tissue Engineering and Regenerative Medicine, 12(2), 330-340. https://doi.org/10.1002/term.2458

Journal Article Type Article
Acceptance Date May 3, 2017
Online Publication Date May 8, 2017
Publication Date Feb 15, 2018
Deposit Date May 9, 2017
Publicly Available Date May 9, 2017
Journal Journal of Tissue Engineering and Regenerative Medicine
Print ISSN 1932-6254
Electronic ISSN 1932-7005
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 12
Issue 2
Pages 330-340
DOI https://doi.org/10.1002/term.2458
Keywords Macrophage, Hydrogel, Cell/Cell interactions, Foreign Body Response, Gelatin, Microenvironment
Public URL http://eprints.nottingham.ac.uk/id/eprint/42662
Publisher URL http://onlinelibrary.wiley.com/doi/10.1002/term.2458/abstract
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf
Additional Information This is the peer reviewed version of the following article: Incorporation of Resident Macrophages in Engineered Tissues: Multiple Cell Type Response to Microenvironment Controlled Macrophage-laden Gelatin Hydrogels / Authors Camille Dollinger, Sait Ciftci, Helena Knopf-Marques, Rabia Guner, Amir M. Ghaemmaghami, Christian Debry, Julien Barth├Ęs, Nihal Engin Vran, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/term.2458. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf


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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf

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