Title
Nanoparticle-driven self-assembling injectable hydrogels provide a multi-factorial approach for chronic wound treatment
Date Issued
15 October 2021
Access level
open access
Resource Type
journal article
Author(s)
Pérez-Rafael S.
Ivanova K.
Stefanov I.
PuiggalĂ J.
Todorova K.
Dimitrov P.
Hinojosa-Caballero D.
Tzanov T.
Universidad Politécnica de Cataluña
Publisher(s)
Acta Materialia Inc
Abstract
Chronic wounds represent a major health burden and drain on medical system. Efficient wound repair is only possible if the dressing materials target simultaneously multiple factors involved in wound chronicity, such as deleterious proteolytic and oxidative enzymes and high bacterial load. Here we develop multifunctional hydrogels for chronic wound management through self-assembling of thiolated hyaluronic acid (HA-SH) and bioactive silver-lignin nanoparticles (Ag@Lig NPs). Dynamic and reversible interactions between the polymer and Ag@Lig NPs yield hybrid nanocomposite hydrogels with shear-thinning and self-healing properties, coupled to zero-order kinetics release of antimicrobial silver in response to infection-related hyalurodinase. The hydrogels inhibit the major enzymes myeloperoxidase and matrix metalloproteinases responsible for wound chronicity in a patient's wound exudate. Furthermore, the lignin-capped AgNPs provide the hydrogel with antioxidant properties and strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The nanocomposite hydrogels are not toxic to human keratinocytes after 7 days of direct contact. Complete tissue remodeling and restoration of skin integrity is demonstrated in vivo in a diabetic mouse model. Hematological analysis reveals lack of wound inflammation due to bacterial infection or toxicity, confirming the potential of HA-SH/Ag@Lig NPs hydrogels for chronic wound management. Statement of significance: Multifunctional hydrogels are promising materials to promote healing of complex wounds. Herein, we report simple and versatile route to prepare biocompatible and multifunctional self-assembled hydrogels for efficient chronic wound treatment utilizing polymer-nanoparticle interactions. Hybrid silver-lignin nanoparticles (Ag@Lig NPs) played both: i) structural role, acting as crosslinking nodes in the hydrogel and endowing it with shear-thinning (ability to flow under applied shear stress) and self-healing properties, and ii) functional role, imparting strong antibacterial and antioxidant activity. Remarkably, the in situ self-assembling of thiolated hyaluronic acid and Ag@Lig NPs yields nanocomposite hydrogels able to simultaneously inhibits the major factors involved in wound chronicity, namely the overexpressed deleterious proteolytic and oxidative enzymes, and high bacterial load.
Start page
131
End page
143
Volume
134
Language
English
OCDE Knowledge area
Ciencia de los polĂmeros
Nano-tecnologĂa
Subjects
Scopus EID
2-s2.0-85115927746
PubMed ID
Source
Acta Biomaterialia
ISSN of the container
17427061
Sponsor(s)
The work was supported by the European project H2020-BBI-JTI- 2017 (Bio-Based Industries); Reinvent, Grant Agreement No.: 792049 and by the Spanish Ministry of Economy and Competitiveness (MINECO, Spain) funded project CoatToSafe PID2019-104111RB-100.
Sources of information:
Directorio de ProducciĂłn CientĂfica
Scopus