Design of the Multi-Bioactive Graphene-Oxide/Gelatin/Alginate Scaffolds as Dual ECM-Mimetic and Specific Wound Healing Phase-Target Therapeutic Concept for Advanced Wound Healing

<b>Objectives:</b> To develop and evaluate graphene oxide/gelatin/alginate scaffolds for advanced wound therapy capable of mimicking the native extracellular matrix (ECM) and bio-stimulating all specific phases of the wound healing process, from inflammation and proliferation to the remo...

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Main Authors: Marko Demenj, Martina Žabčić, Marija Vukomanović, Tatjana Ilić-Tomić, Dušan Milivojević, Simonida Tomić, Dubravka Živanović, Marija M. Babić Radić
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Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/1/89
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author Marko Demenj
Martina Žabčić
Marija Vukomanović
Tatjana Ilić-Tomić
Dušan Milivojević
Simonida Tomić
Dubravka Živanović
Marija M. Babić Radić
author_facet Marko Demenj
Martina Žabčić
Marija Vukomanović
Tatjana Ilić-Tomić
Dušan Milivojević
Simonida Tomić
Dubravka Živanović
Marija M. Babić Radić
author_sort Marko Demenj
collection DOAJ
description <b>Objectives:</b> To develop and evaluate graphene oxide/gelatin/alginate scaffolds for advanced wound therapy capable of mimicking the native extracellular matrix (ECM) and bio-stimulating all specific phases of the wound healing process, from inflammation and proliferation to the remodeling of damaged skin tissue in three dimensions. <b>Methods:</b> The scaffolds were engineered as interpenetrating polymeric networks by the crosslinking reaction of gelatin in the presence of alginate and characterized by structural, morphological, mechanical, swelling properties, porosity, adhesion to the skin tissue, wettability, and in vitro simultaneous release of the active agents. Biocompatibility of the scaffolds were evaluated in vitro by MTT test on fibroblasts (MRC5 cells) and in vivo using <i>Caenorhabditis elegans</i> assay. <b>Results:</b> The scaffolds exhibited a highly porous interconnected morphology with adjustable porosity (93–96%) and mechanical strength (1.10–2.90 MPa), hydrophilic nature with high capacity to absorb physiological fluids, and stable adhesion to the skin tissue. The obtained results of MRC5 cell viability indicate that the scaffolds are safe for biomedical applications. No mortality was detected among the <i>Caenorhabditis elegans</i> throughout the incubation period, indicating that the scaffolds are not toxic. The results of in vitro release study of allantoin, quercetin, and caffeic acid confirm the scaffolds’ significant potential for simultaneous release. <b>Conclusion:</b> The graphene oxide/gelatin/alginate scaffolds are promising candidates for non-invasive, dual ECM-mimetic, and multi-target wound therapy, offering an innovative strategy to address the complexities of wound healing process.
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spelling doaj-art-a3f626d90791432abde5c5beec36fd302025-01-24T13:45:54ZengMDPI AGPharmaceutics1999-49232025-01-011718910.3390/pharmaceutics17010089Design of the Multi-Bioactive Graphene-Oxide/Gelatin/Alginate Scaffolds as Dual ECM-Mimetic and Specific Wound Healing Phase-Target Therapeutic Concept for Advanced Wound HealingMarko Demenj0Martina Žabčić1Marija Vukomanović2Tatjana Ilić-Tomić3Dušan Milivojević4Simonida Tomić5Dubravka Živanović6Marija M. Babić Radić7University of Belgrade, University Clinical Center of Serbia, Clinic of Dermatology and Venereology, Pasterova 2, 11000 Belgrade, SerbiaAdvanced Materials Department, Jožef Stefan Institute, Jamova Cesta 39, 1000 Ljubljana, SloveniaAdvanced Materials Department, Jožef Stefan Institute, Jamova Cesta 39, 1000 Ljubljana, SloveniaUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11000 Belgrade, SerbiaUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11000 Belgrade, SerbiaUniversity of Belgrade, Faculty of Technology and Metallurgy, Karnegijeva 4, 11000 Belgrade, SerbiaUniversity of Belgrade, University Clinical Center of Serbia, Clinic of Dermatology and Venereology, Pasterova 2, 11000 Belgrade, SerbiaUniversity of Belgrade, Faculty of Technology and Metallurgy, Karnegijeva 4, 11000 Belgrade, Serbia<b>Objectives:</b> To develop and evaluate graphene oxide/gelatin/alginate scaffolds for advanced wound therapy capable of mimicking the native extracellular matrix (ECM) and bio-stimulating all specific phases of the wound healing process, from inflammation and proliferation to the remodeling of damaged skin tissue in three dimensions. <b>Methods:</b> The scaffolds were engineered as interpenetrating polymeric networks by the crosslinking reaction of gelatin in the presence of alginate and characterized by structural, morphological, mechanical, swelling properties, porosity, adhesion to the skin tissue, wettability, and in vitro simultaneous release of the active agents. Biocompatibility of the scaffolds were evaluated in vitro by MTT test on fibroblasts (MRC5 cells) and in vivo using <i>Caenorhabditis elegans</i> assay. <b>Results:</b> The scaffolds exhibited a highly porous interconnected morphology with adjustable porosity (93–96%) and mechanical strength (1.10–2.90 MPa), hydrophilic nature with high capacity to absorb physiological fluids, and stable adhesion to the skin tissue. The obtained results of MRC5 cell viability indicate that the scaffolds are safe for biomedical applications. No mortality was detected among the <i>Caenorhabditis elegans</i> throughout the incubation period, indicating that the scaffolds are not toxic. The results of in vitro release study of allantoin, quercetin, and caffeic acid confirm the scaffolds’ significant potential for simultaneous release. <b>Conclusion:</b> The graphene oxide/gelatin/alginate scaffolds are promising candidates for non-invasive, dual ECM-mimetic, and multi-target wound therapy, offering an innovative strategy to address the complexities of wound healing process.https://www.mdpi.com/1999-4923/17/1/89polymeric scaffoldsgelatin/alinate based scaffoldsECM-mimetic wound therapymulti-target wound therapyallantoincaffeic acid
spellingShingle Marko Demenj
Martina Žabčić
Marija Vukomanović
Tatjana Ilić-Tomić
Dušan Milivojević
Simonida Tomić
Dubravka Živanović
Marija M. Babić Radić
Design of the Multi-Bioactive Graphene-Oxide/Gelatin/Alginate Scaffolds as Dual ECM-Mimetic and Specific Wound Healing Phase-Target Therapeutic Concept for Advanced Wound Healing
Pharmaceutics
polymeric scaffolds
gelatin/alinate based scaffolds
ECM-mimetic wound therapy
multi-target wound therapy
allantoin
caffeic acid
title Design of the Multi-Bioactive Graphene-Oxide/Gelatin/Alginate Scaffolds as Dual ECM-Mimetic and Specific Wound Healing Phase-Target Therapeutic Concept for Advanced Wound Healing
title_full Design of the Multi-Bioactive Graphene-Oxide/Gelatin/Alginate Scaffolds as Dual ECM-Mimetic and Specific Wound Healing Phase-Target Therapeutic Concept for Advanced Wound Healing
title_fullStr Design of the Multi-Bioactive Graphene-Oxide/Gelatin/Alginate Scaffolds as Dual ECM-Mimetic and Specific Wound Healing Phase-Target Therapeutic Concept for Advanced Wound Healing
title_full_unstemmed Design of the Multi-Bioactive Graphene-Oxide/Gelatin/Alginate Scaffolds as Dual ECM-Mimetic and Specific Wound Healing Phase-Target Therapeutic Concept for Advanced Wound Healing
title_short Design of the Multi-Bioactive Graphene-Oxide/Gelatin/Alginate Scaffolds as Dual ECM-Mimetic and Specific Wound Healing Phase-Target Therapeutic Concept for Advanced Wound Healing
title_sort design of the multi bioactive graphene oxide gelatin alginate scaffolds as dual ecm mimetic and specific wound healing phase target therapeutic concept for advanced wound healing
topic polymeric scaffolds
gelatin/alinate based scaffolds
ECM-mimetic wound therapy
multi-target wound therapy
allantoin
caffeic acid
url https://www.mdpi.com/1999-4923/17/1/89
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