PROMOTION OF WOUND HEALING THROUGH CAZN-RELEASING NANOPARTICLES; IN VITRO STUDIES

Not scheduled
20m
ICE Krakow

ICE Krakow

ul. Marii Konopnickiej 17 30-302 Kraków

Speaker

Ximenes-Carballo, Celia (Institute for Bioengineering of Catalonia (IBEC))

Description

"Introduction: Chronic wounds represent a major burden in human society, and their prevalence is expected to increase due to the upward trend of an aging population, incidence of diabetes, and obesity. In Europe, one out of five hospitalized patients suffers from a pressure ulcer. Moreover, the costs associated with its extensive care treatments are high; about 25 billion dollars are spent annually in the US1. These costs can be reduced by appropriate diagnosis and treatment. However, a device that enables fast-effective closure, low cost, and scalability is still missing.
Ions such as calcium (Ca2+) and zinc (Zn2+) are essential for skin homeostasis. It is well known that calcium regulates platelet aggregation and epidermal stratification. We have shown that calcium phosphate nanoparticles (NPs) stimulated wound healing both in vitro and in vivo 2,3. On the other hand, zinc deficiencies are associated with impaired wound healing and roughened skin. Zinc’s antimicrobial properties have been recently suggested 4,5, making this ion promising for its application on wound dressings.
This work aims to develop an ion releasing platform based on nanocomposites for local and sustained calcium and zinc release at the wound site, to achieve wound closure and prevent microbial growth.

Methods: Submicrometric particles incorporating different amounts of Zn2+ and Ca2+ ions were developed. Ion release was analyzed by colorimetric methods. Particle size was determined by Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM). Particle composition was studied using X-Ray Diffraction and Energy Dispersive X-Ray Spectroscopy (SEM-EDX). Direct and indirect particle toxicity was assessed in vitro in human dermal fibroblasts (hDFs) and human keratinocytes (hKCs) using the MTT assay. Cell migration was studied using the scratch wound assay. Collagen deposition and wound contraction were assessed by hydroxyproline assay and a fibroblasts-populated collagen lattice, respectively. Matrix metalloproteinases (MMP) production was studied by zymography.

Results and Discussion: Calcium and zinc were successfully incorporated into the particles with high reproducibility. Different compositions of Zn2+ and Ca2+ were combined successfully. Particles showed a rounded morphology, with submicronic sizes. Backscattering images show that zinc and calcium are homogeneously mixed. Ion release was sustained for up to 1 month (assay endpoint). Particles with lower Zn content showed better biocompatibility compared to higher ones. In vitro, particles promoted cell migration and collagen deposition. MMPs were not activated in the presence of nanoparticles.

Conclusion: Ion releasing platforms were successfully produced. Their composition, size, and ion release profiles as well as their in vitro performance indicate their potential use in wound healing therapies.

Acknowledgments: This work was supported by the European Commission-Euronanomed nAngioderm Project (JTC2018-103) funded through the Spanish Ministry of Science and Innovation (ref. PCI2019-103648).

References:
1. Frenk, J. Harvard International Review 35, 62–64 (2014).
2. Navarro-Requena, C. & Pérez-Amodio, S. Nanotechnology (2018) doi:10.1088/1361-6528/aad01f.
3. Perez-Amodio, S. et al. Advances in Wound Care 00, 1–3 (2020).
4. Pasquet, J. et al. Colloids and Surfaces A: Physicochemical and Engineering Aspects 457, 263–274 (2014).
5. Chiriac, V. et al. IOP Conference Series: MSE 133, (2016)."
20941851667

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