Subcutaneous Application of a Gelatin/Hyaluronic Acid Hydrogel Induces the Production of Skin Extracellular Matrix

The development of injectable hydrogels with natural biopolymers such as gelatin (Ge) and hyaluronic acid (Ha) is widely performed due to their biocompatibility and biodegradability. The combination of both polymers crosslinked with N-Ethyl-N′-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC...

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Main Authors: Katia Jarquín-Yáñez, Miguel Ángel Herrera-Enríquez, Diego Ivan Benítez-Barrera, Francisco M. Sánchez-Arévalo, Jorge Alejandro Benítez-Martínez, Gabriela Piñón-Zárate, Beatriz Hernández-Téllez, Diana M. Aguilar Sandoval, Andrés E. Castell-Rodríguez
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Polymers
Subjects:
Online Access:https://www.mdpi.com/2073-4360/16/5/573
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author Katia Jarquín-Yáñez
Miguel Ángel Herrera-Enríquez
Diego Ivan Benítez-Barrera
Francisco M. Sánchez-Arévalo
Jorge Alejandro Benítez-Martínez
Gabriela Piñón-Zárate
Beatriz Hernández-Téllez
Diana M. Aguilar Sandoval
Andrés E. Castell-Rodríguez
author_facet Katia Jarquín-Yáñez
Miguel Ángel Herrera-Enríquez
Diego Ivan Benítez-Barrera
Francisco M. Sánchez-Arévalo
Jorge Alejandro Benítez-Martínez
Gabriela Piñón-Zárate
Beatriz Hernández-Téllez
Diana M. Aguilar Sandoval
Andrés E. Castell-Rodríguez
author_sort Katia Jarquín-Yáñez
collection DOAJ
description The development of injectable hydrogels with natural biopolymers such as gelatin (Ge) and hyaluronic acid (Ha) is widely performed due to their biocompatibility and biodegradability. The combination of both polymers crosslinked with N-Ethyl-N′-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) can be used as an innovative dermal filler that stimulates fibroblast activity and increases skin elasticity and tightness. Thus, crosslinked Ge/Ha hydrogels with different concentrations of EDC were administered subcutaneously to test their efficacy in young and old rats. At higher EDC concentrations, the viscosity decreases while the particle size of the hydrogels increases. At all concentrations of EDC, amino and carboxyl groups are present. The histological analysis shows an acute inflammatory response, which disappears seven days after application. At one and three months post-treatment, no remains of the hydrogels are found, and the number of fibroblasts increases in all groups in comparison with the control. In addition, the elastic modulus of the skin increases after three months of treatment. Because EDC-crosslinked Ge/Ha hydrogels are biocompatible and induce increased skin tension, fibroblast proliferation, and de novo extracellular matrix production, we propose their use as a treatment to attenuate wrinkles and expression lines.
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spelling doaj.art-ddd6dcf9031b4911bc0a1dedf35806662024-03-12T16:53:16ZengMDPI AGPolymers2073-43602024-02-0116557310.3390/polym16050573Subcutaneous Application of a Gelatin/Hyaluronic Acid Hydrogel Induces the Production of Skin Extracellular MatrixKatia Jarquín-Yáñez0Miguel Ángel Herrera-Enríquez1Diego Ivan Benítez-Barrera2Francisco M. Sánchez-Arévalo3Jorge Alejandro Benítez-Martínez4Gabriela Piñón-Zárate5Beatriz Hernández-Téllez6Diana M. Aguilar Sandoval7Andrés E. Castell-Rodríguez8Facultad de Medicina, National Autonomous University of Mexico, Mexico City 04510, MexicoFacultad de Medicina, National Autonomous University of Mexico, Mexico City 04510, MexicoMaterials Research Institute, National Autonomous University of Mexico, Mexico City 04510, MexicoMaterials Research Institute, National Autonomous University of Mexico, Mexico City 04510, MexicoMaterials Research Institute, National Autonomous University of Mexico, Mexico City 04510, MexicoFacultad de Medicina, National Autonomous University of Mexico, Mexico City 04510, MexicoFacultad de Medicina, National Autonomous University of Mexico, Mexico City 04510, MexicoFacultad de Medicina, National Autonomous University of Mexico, Mexico City 04510, MexicoFacultad de Medicina, National Autonomous University of Mexico, Mexico City 04510, MexicoThe development of injectable hydrogels with natural biopolymers such as gelatin (Ge) and hyaluronic acid (Ha) is widely performed due to their biocompatibility and biodegradability. The combination of both polymers crosslinked with N-Ethyl-N′-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) can be used as an innovative dermal filler that stimulates fibroblast activity and increases skin elasticity and tightness. Thus, crosslinked Ge/Ha hydrogels with different concentrations of EDC were administered subcutaneously to test their efficacy in young and old rats. At higher EDC concentrations, the viscosity decreases while the particle size of the hydrogels increases. At all concentrations of EDC, amino and carboxyl groups are present. The histological analysis shows an acute inflammatory response, which disappears seven days after application. At one and three months post-treatment, no remains of the hydrogels are found, and the number of fibroblasts increases in all groups in comparison with the control. In addition, the elastic modulus of the skin increases after three months of treatment. Because EDC-crosslinked Ge/Ha hydrogels are biocompatible and induce increased skin tension, fibroblast proliferation, and de novo extracellular matrix production, we propose their use as a treatment to attenuate wrinkles and expression lines.https://www.mdpi.com/2073-4360/16/5/573hydrogelsEDCskin fillersbiocompatible materialstissue engineering
spellingShingle Katia Jarquín-Yáñez
Miguel Ángel Herrera-Enríquez
Diego Ivan Benítez-Barrera
Francisco M. Sánchez-Arévalo
Jorge Alejandro Benítez-Martínez
Gabriela Piñón-Zárate
Beatriz Hernández-Téllez
Diana M. Aguilar Sandoval
Andrés E. Castell-Rodríguez
Subcutaneous Application of a Gelatin/Hyaluronic Acid Hydrogel Induces the Production of Skin Extracellular Matrix
Polymers
hydrogels
EDC
skin fillers
biocompatible materials
tissue engineering
title Subcutaneous Application of a Gelatin/Hyaluronic Acid Hydrogel Induces the Production of Skin Extracellular Matrix
title_full Subcutaneous Application of a Gelatin/Hyaluronic Acid Hydrogel Induces the Production of Skin Extracellular Matrix
title_fullStr Subcutaneous Application of a Gelatin/Hyaluronic Acid Hydrogel Induces the Production of Skin Extracellular Matrix
title_full_unstemmed Subcutaneous Application of a Gelatin/Hyaluronic Acid Hydrogel Induces the Production of Skin Extracellular Matrix
title_short Subcutaneous Application of a Gelatin/Hyaluronic Acid Hydrogel Induces the Production of Skin Extracellular Matrix
title_sort subcutaneous application of a gelatin hyaluronic acid hydrogel induces the production of skin extracellular matrix
topic hydrogels
EDC
skin fillers
biocompatible materials
tissue engineering
url https://www.mdpi.com/2073-4360/16/5/573
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