Gelatin-/Alginate-Based Hydrogel Scaffolds Reinforced with TiO<sub>2</sub> Nanoparticles for Simultaneous Release of Allantoin, Caffeic Acid, and Quercetin as Multi-Target Wound Therapy Platform

This study proposes synthesis and evaluation of gelatin-/alginate-based hydrogel scaffolds reinforced with titanium dioxide (TiO<sub>2</sub>) nanoparticles which, through their combination with allantoin, quercetin, and caffeic acid, provide multi-target therapy directed on all phases of...

Full description

Bibliographic Details
Main Authors: Marija M. Babić Radić, Marija Vukomanović, Jasmina Nikodinović-Runić, Simonida Tomić
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/16/3/372
_version_ 1797239663793012736
author Marija M. Babić Radić
Marija Vukomanović
Jasmina Nikodinović-Runić
Simonida Tomić
author_facet Marija M. Babić Radić
Marija Vukomanović
Jasmina Nikodinović-Runić
Simonida Tomić
author_sort Marija M. Babić Radić
collection DOAJ
description This study proposes synthesis and evaluation of gelatin-/alginate-based hydrogel scaffolds reinforced with titanium dioxide (TiO<sub>2</sub>) nanoparticles which, through their combination with allantoin, quercetin, and caffeic acid, provide multi-target therapy directed on all phases of the wound healing process. These scaffolds provide the simultaneous release of bioactive agents and concurrently support cell/tissue repair through the replicated structure of a native extracellular matrix. The hydrogel scaffolds were synthesized via a crosslinking reaction using EDC as a crosslinker for gelatin. Synthesized hydrogel scaffolds and the effect of TiO<sub>2</sub> on their properties were characterized by structural, mechanical, morphological, and swelling properties, and the porosity, wettability, adhesion to skin tissue, and simultaneous release features. The biocompatibility of the scaffolds was tested in vitro on fibroblasts (MRC5 cells) and in vivo (<i>Caenorhabditis elegans</i>) in a survival probe. The scaffolds revealed porous interconnected morphology, porosity of 88.33 to 96.76%, elastic modulus of 1.53 to 4.29 MPa, full hydrophilicity, favorable skin adhesivity, and biocompatibility. The simultaneous release was investigated in vitro indicating dependence on the scaffold’s composition and type of bioactive agents. The novel scaffolds designed as multi-target therapy have significant promise for improved wound healing in a beneficial and non-invasive manner.
first_indexed 2024-04-24T17:55:07Z
format Article
id doaj.art-76eb5c3f673f4f109b40a18f571144e8
institution Directory Open Access Journal
issn 1999-4923
language English
last_indexed 2024-04-24T17:55:07Z
publishDate 2024-03-01
publisher MDPI AG
record_format Article
series Pharmaceutics
spelling doaj.art-76eb5c3f673f4f109b40a18f571144e82024-03-27T13:59:44ZengMDPI AGPharmaceutics1999-49232024-03-0116337210.3390/pharmaceutics16030372Gelatin-/Alginate-Based Hydrogel Scaffolds Reinforced with TiO<sub>2</sub> Nanoparticles for Simultaneous Release of Allantoin, Caffeic Acid, and Quercetin as Multi-Target Wound Therapy PlatformMarija M. Babić Radić0Marija Vukomanović1Jasmina Nikodinović-Runić2Simonida Tomić3University of Belgrade, Faculty of Technology and Metallurgy, Karnegijeva 4, 11000 Belgrade, SerbiaAdvanced 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, Faculty of Technology and Metallurgy, Karnegijeva 4, 11000 Belgrade, SerbiaThis study proposes synthesis and evaluation of gelatin-/alginate-based hydrogel scaffolds reinforced with titanium dioxide (TiO<sub>2</sub>) nanoparticles which, through their combination with allantoin, quercetin, and caffeic acid, provide multi-target therapy directed on all phases of the wound healing process. These scaffolds provide the simultaneous release of bioactive agents and concurrently support cell/tissue repair through the replicated structure of a native extracellular matrix. The hydrogel scaffolds were synthesized via a crosslinking reaction using EDC as a crosslinker for gelatin. Synthesized hydrogel scaffolds and the effect of TiO<sub>2</sub> on their properties were characterized by structural, mechanical, morphological, and swelling properties, and the porosity, wettability, adhesion to skin tissue, and simultaneous release features. The biocompatibility of the scaffolds was tested in vitro on fibroblasts (MRC5 cells) and in vivo (<i>Caenorhabditis elegans</i>) in a survival probe. The scaffolds revealed porous interconnected morphology, porosity of 88.33 to 96.76%, elastic modulus of 1.53 to 4.29 MPa, full hydrophilicity, favorable skin adhesivity, and biocompatibility. The simultaneous release was investigated in vitro indicating dependence on the scaffold’s composition and type of bioactive agents. The novel scaffolds designed as multi-target therapy have significant promise for improved wound healing in a beneficial and non-invasive manner.https://www.mdpi.com/1999-4923/16/3/372hydrogel scaffoldsgelatin-/alginate-based scaffoldssustained releasewound healingallantoincaffeic acid
spellingShingle Marija M. Babić Radić
Marija Vukomanović
Jasmina Nikodinović-Runić
Simonida Tomić
Gelatin-/Alginate-Based Hydrogel Scaffolds Reinforced with TiO<sub>2</sub> Nanoparticles for Simultaneous Release of Allantoin, Caffeic Acid, and Quercetin as Multi-Target Wound Therapy Platform
Pharmaceutics
hydrogel scaffolds
gelatin-/alginate-based scaffolds
sustained release
wound healing
allantoin
caffeic acid
title Gelatin-/Alginate-Based Hydrogel Scaffolds Reinforced with TiO<sub>2</sub> Nanoparticles for Simultaneous Release of Allantoin, Caffeic Acid, and Quercetin as Multi-Target Wound Therapy Platform
title_full Gelatin-/Alginate-Based Hydrogel Scaffolds Reinforced with TiO<sub>2</sub> Nanoparticles for Simultaneous Release of Allantoin, Caffeic Acid, and Quercetin as Multi-Target Wound Therapy Platform
title_fullStr Gelatin-/Alginate-Based Hydrogel Scaffolds Reinforced with TiO<sub>2</sub> Nanoparticles for Simultaneous Release of Allantoin, Caffeic Acid, and Quercetin as Multi-Target Wound Therapy Platform
title_full_unstemmed Gelatin-/Alginate-Based Hydrogel Scaffolds Reinforced with TiO<sub>2</sub> Nanoparticles for Simultaneous Release of Allantoin, Caffeic Acid, and Quercetin as Multi-Target Wound Therapy Platform
title_short Gelatin-/Alginate-Based Hydrogel Scaffolds Reinforced with TiO<sub>2</sub> Nanoparticles for Simultaneous Release of Allantoin, Caffeic Acid, and Quercetin as Multi-Target Wound Therapy Platform
title_sort gelatin alginate based hydrogel scaffolds reinforced with tio sub 2 sub nanoparticles for simultaneous release of allantoin caffeic acid and quercetin as multi target wound therapy platform
topic hydrogel scaffolds
gelatin-/alginate-based scaffolds
sustained release
wound healing
allantoin
caffeic acid
url https://www.mdpi.com/1999-4923/16/3/372
work_keys_str_mv AT marijambabicradic gelatinalginatebasedhydrogelscaffoldsreinforcedwithtiosub2subnanoparticlesforsimultaneousreleaseofallantoincaffeicacidandquercetinasmultitargetwoundtherapyplatform
AT marijavukomanovic gelatinalginatebasedhydrogelscaffoldsreinforcedwithtiosub2subnanoparticlesforsimultaneousreleaseofallantoincaffeicacidandquercetinasmultitargetwoundtherapyplatform
AT jasminanikodinovicrunic gelatinalginatebasedhydrogelscaffoldsreinforcedwithtiosub2subnanoparticlesforsimultaneousreleaseofallantoincaffeicacidandquercetinasmultitargetwoundtherapyplatform
AT simonidatomic gelatinalginatebasedhydrogelscaffoldsreinforcedwithtiosub2subnanoparticlesforsimultaneousreleaseofallantoincaffeicacidandquercetinasmultitargetwoundtherapyplatform