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IL-4 Release from a Biomimetic Scaffold for the Temporally Controlled Modulation of Macrophage Response

  • Emerging Trends in Biomaterials Research
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Abstract

The interaction of immune cells with biomaterials has been identified as a possible predictor of either the success or the failure of the implant. Among immune cells, macrophages have been found to contribute to both of these possible scenarios, based on their polarization profile. This proof-of-concept study aimed to investigate if it was possible to affect the response of macrophages to biomaterials, by the release of anti-inflammatory mediators. Towards this end, a collagen scaffold, integrated with poly(lactic-co-glycolic acid)—multistage silicon particles (MSV) composite microspheres (PLGA-MSV) releasing IL-4 was developed (PLGA-MSV/IL-4). Macrophages’ response to the scaffold was evaluated, both in vitro with rat bone-marrow derived macrophages, and in vivo in a rat subcutaneous pouch model. In vitro experiments revealed an overexpression of anti-inflammatory associated genes (Il-10, Mrc1, Arg1) at as soon as 48 h. The analysis of the cells that infiltrated the scaffold, revealed a prevalence of CD206+ macrophages at 24 h. Our strategy demonstrated that it is possible to tune the in vivo early response to biomaterials by the release of an anti-inflammatory cytokine, and that could contribute to accelerate the resolution of the inflammatory phase, benefiting a vast range of tissue engineering applications.

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Abbreviations

BMDM:

Bone marrow-derived macrophages

MSV:

Multistage porous silicon particle vectors

PLGA:

Poly(dl-lactide-co-glycolide) acid

PLGA-MSV:

PLGA-porous silicon particles composite microspheres

PLGA-MSV/IL-4:

PLGA-MSV releasing IL-4

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Acknowledgments

This study was supported by the Brown Foundation (Project ID, 18130011), the Cullen Foundation (Project ID, 18130014). The work was supported by funds from the Houston Methodist Research Institute. Partial funds were acquired from the Ernest Cockrell Jr. Presidential Distinguished Chair (M.F.). We thank Dr. J. Gu, director of the HMRI Microscopy-SEM/AFM core, Dr. K. Cui, director of the HMRI ACTM core and Dr. D. Haviland, director of the HMRI Flow Cytometry core. We thank Dr. Xin Wang for her help troubleshooting the gene expression study.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Avenue, Houston, TX, 77030, USA

    Silvia Minardi, Bruna Corradetti, Francesca Taraballi, Jae Hyuk Byun, Fernando Cabrera & Ennio Tasciotti

  2. Department of Life and Environmental Sciences, Università Politecnica delle Marche, via Brecce Bianche, 60131, Ancona, Italy

    Bruna Corradetti

  3. Department of Nanomedicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Avenue, Houston, TX, 77030, USA

    Xeuwu Liu & Mauro Ferrari

  4. Department of Orthopaedics, Houston Methodist Hospital (HMH), 6550 Fannin St, Houston, TX, 77030, USA

    Bradley K. Weiner

  5. The Surgical Advanced Technology Laboratory, Houston Methodist Research Institute (HMRI), 6670 Bertner Ave, Houston, TX, 77030, USA

    Bradley K. Weiner & Ennio Tasciotti

Authors
  1. Silvia Minardi
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  2. Bruna Corradetti
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  3. Francesca Taraballi
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  4. Jae Hyuk Byun
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  6. Xeuwu Liu
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  7. Mauro Ferrari
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  8. Bradley K. Weiner
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  9. Ennio Tasciotti
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Corresponding author

Correspondence to Ennio Tasciotti.

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Associate Editor Michael S. Detamore oversaw the review of this article.

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Minardi, S., Corradetti, B., Taraballi, F. et al. IL-4 Release from a Biomimetic Scaffold for the Temporally Controlled Modulation of Macrophage Response. Ann Biomed Eng 44, 2008–2019 (2016). https://doi.org/10.1007/s10439-016-1580-z

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  • DOI: https://doi.org/10.1007/s10439-016-1580-z

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