Overcoming the Inflammatory Stage of Non-Healing Wounds: In Vitro Mechanism of Action of Negatively Charged Microspheres (NCMs)

Santos-Vizcaino, Edorta; Salvador, Aiala; Vairo, Claudia; Igartua, Manoli; Hernandez, Rosa Maria; Correa, Luis; Villullas, Silvia; Gainza, Garazi

doi:10.3390/nano10061108

Open AccessArticle

Overcoming the Inflammatory Stage of Non-Healing Wounds: In Vitro Mechanism of Action of Negatively Charged Microspheres (NCMs)

by

Edorta Santos-Vizcaino

^1,2,†

,

Aiala Salvador

^1,2,†,

Claudia Vairo

^1,3,*,

Manoli Igartua

^1,2

,

Rosa Maria Hernandez

^1,2

,

Luis Correa

⁴,

Silvia Villullas

³ and

Garazi Gainza

^3,*

¹

NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain

²

Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 01006 Vitoria-Gasteiz, Spain

³

BioKeralty Research Institute AIE, Albert Einstein, 25-E3, 01510 Miñano, Spain

⁴

Praxis Pharmaceutical, San Fernando de Henares Business Park, Avenida de Castilla 2, Dublin Building 2nd floor, San Fernando de Henares, 28830 Madrid, Spain

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Nanomaterials 2020, 10(6), 1108; https://doi.org/10.3390/nano10061108

Submission received: 9 May 2020 / Revised: 23 May 2020 / Accepted: 1 June 2020 / Published: 3 June 2020

(This article belongs to the Special Issue Nanoparticle-Macrophage Interactions: Implications for Nanosafety and Nanomedicine)

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Abstract

Negatively charged microspheres (NCMs) represent a new therapeutic approach for wound healing since recent clinical trials have shown NCM efficacy in the recovery of hard-to-heal wounds that tend to stay in the inflammatory phase, unlocking the healing process. The aim of this study was to elucidate the NCM mechanism of action. NCMs were extracted from a commercial microsphere formulation (PolyHeal^® Micro) and cytotoxicity, attachment, proliferation and viability assays were performed in keratinocytes and dermal fibroblasts, while macrophages were used for the phagocytosis and polarization assays. We demonstrated that cells tend to attach to the microsphere surface, and that NCMs are biocompatible and promote cell proliferation at specific concentrations (50 and 10 NCM/cell) by a minimum of 3 fold compared to the control group. Furthermore, NCM internalization by macrophages seemed to drive these cells to a noninflammatory condition, as demonstrated by the over-expression of CD206 and the under-expression of CD64, M2 and M1 markers, respectively. NCMs are an effective approach for reverting the chronic inflammatory state of stagnant wounds (such as diabetic wounds) and thus for improving wound healing.

Keywords: chronic wound; device; foot ulcer; inflammation; wound healing; macrophage

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MDPI and ACS Style

Santos-Vizcaino, E.; Salvador, A.; Vairo, C.; Igartua, M.; Hernandez, R.M.; Correa, L.; Villullas, S.; Gainza, G. Overcoming the Inflammatory Stage of Non-Healing Wounds: In Vitro Mechanism of Action of Negatively Charged Microspheres (NCMs). Nanomaterials 2020, 10, 1108. https://doi.org/10.3390/nano10061108

AMA Style

Santos-Vizcaino E, Salvador A, Vairo C, Igartua M, Hernandez RM, Correa L, Villullas S, Gainza G. Overcoming the Inflammatory Stage of Non-Healing Wounds: In Vitro Mechanism of Action of Negatively Charged Microspheres (NCMs). Nanomaterials. 2020; 10(6):1108. https://doi.org/10.3390/nano10061108

Chicago/Turabian Style

Santos-Vizcaino, Edorta, Aiala Salvador, Claudia Vairo, Manoli Igartua, Rosa Maria Hernandez, Luis Correa, Silvia Villullas, and Garazi Gainza. 2020. "Overcoming the Inflammatory Stage of Non-Healing Wounds: In Vitro Mechanism of Action of Negatively Charged Microspheres (NCMs)" Nanomaterials 10, no. 6: 1108. https://doi.org/10.3390/nano10061108

APA Style

Santos-Vizcaino, E., Salvador, A., Vairo, C., Igartua, M., Hernandez, R. M., Correa, L., Villullas, S., & Gainza, G. (2020). Overcoming the Inflammatory Stage of Non-Healing Wounds: In Vitro Mechanism of Action of Negatively Charged Microspheres (NCMs). Nanomaterials, 10(6), 1108. https://doi.org/10.3390/nano10061108

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Overcoming the Inflammatory Stage of Non-Healing Wounds: In Vitro Mechanism of Action of Negatively Charged Microspheres (NCMs)

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