Design and Evaluation of a Crosslinked Chitosan-Based Scaffold Containing Hyaluronic Acid for Articular Cartilage Reconstruction

Polymeric scaffolds are promising in tissue engineering due to their structural similarity to extracellular matrix components. This study aimed to design freeze-dried hydrogels based on chitosan (CHT) and hyaluronic acid (HA). Chitosan-based gels were crosslinked with oxidized maltodextrin (MDo) bef...

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Main Authors: Salim Hamidi, Mickael Maton, Feng Hildebrand, Valérie Gaucher, Cédric Bossard, Frédéric Cazaux, Jean Noel Staelens, Nicolas Blanchemain, Bernard Martel
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/10/2202
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author Salim Hamidi
Mickael Maton
Feng Hildebrand
Valérie Gaucher
Cédric Bossard
Frédéric Cazaux
Jean Noel Staelens
Nicolas Blanchemain
Bernard Martel
author_facet Salim Hamidi
Mickael Maton
Feng Hildebrand
Valérie Gaucher
Cédric Bossard
Frédéric Cazaux
Jean Noel Staelens
Nicolas Blanchemain
Bernard Martel
author_sort Salim Hamidi
collection DOAJ
description Polymeric scaffolds are promising in tissue engineering due to their structural similarity to extracellular matrix components. This study aimed to design freeze-dried hydrogels based on chitosan (CHT) and hyaluronic acid (HA). Chitosan-based gels were crosslinked with oxidized maltodextrin (MDo) before the freeze-drying step, resulting in spongy porous scaffolds. Based on the state-of-the-art, our hypothesis was that crosslinking would increase scaffold stiffness and delay the degradation of the CHT:HA resorbable scaffolds swelled in a hydrated physiological environment. The physicochemical and mechanical properties of crosslinked CHT- and CHT:HA-based scaffolds were analyzed. Hygroscopic and swelling behavior were assessed using dynamic vapor sorption analysis and batch studies. Degradation was evaluated under different conditions, including in phosphate-buffered saline (PBS), PBS with lysozyme, and lactic acid solutions, to investigate scaffold resistance against enzymatic and acidic degradation. The porosity of the spongy materials was characterized using scanning electron microscopy, while dynamic mechanical analysis provided information on the mechanical properties. Crosslinked scaffolds showed reduced swelling, slower degradation rates, and increased stiffness, confirming MDo as an effective crosslinking agent. Scaffolds loaded with ciprofloxacin (CFX) demonstrated their ability to deliver therapeutic agents, as the CFX loading capacity was promoted by CHT–CFX interactions. Microbiologic investigation confirmed the results. Finally, cytotoxicity tests displayed no toxicity. In conclusion, MDo-crosslinked CHT and CHT:HA scaffolds exhibit enhanced stability, functionality, and mechanical performance, making them promising for cartilage tissue engineering.
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spelling doaj-art-2f0231de38324aba824fa80b10fcb9d92025-08-20T03:47:58ZengMDPI AGMolecules1420-30492025-05-013010220210.3390/molecules30102202Design and Evaluation of a Crosslinked Chitosan-Based Scaffold Containing Hyaluronic Acid for Articular Cartilage ReconstructionSalim Hamidi0Mickael Maton1Feng Hildebrand2Valérie Gaucher3Cédric Bossard4Frédéric Cazaux5Jean Noel Staelens6Nicolas Blanchemain7Bernard Martel8Univ. Lille, INSERM, CHU Lille, U1008-Advanced Drug Delivery Systems and Biomaterials, F-59000 Lille, FranceUniv. Lille, INSERM, CHU Lille, U1008-Advanced Drug Delivery Systems and Biomaterials, F-59000 Lille, FranceUniv. Lille, INSERM, CHU Lille, U1008-Advanced Drug Delivery Systems and Biomaterials, F-59000 Lille, FranceUniv. Lille, CNRS, INRAE, Centrale Lille, UMR 8207—UMET—Unité Matériaux et Transformations, F-59000 Lille, FranceUniv. Lille, INSERM, CHU Lille, U1008-Advanced Drug Delivery Systems and Biomaterials, F-59000 Lille, FranceUniv. Lille, CNRS, INRAE, Centrale Lille, UMR 8207—UMET—Unité Matériaux et Transformations, F-59000 Lille, FranceUniv. Lille, CNRS, INRAE, Centrale Lille, UMR 8207—UMET—Unité Matériaux et Transformations, F-59000 Lille, FranceUniv. Lille, INSERM, CHU Lille, U1008-Advanced Drug Delivery Systems and Biomaterials, F-59000 Lille, FranceUniv. Lille, CNRS, INRAE, Centrale Lille, UMR 8207—UMET—Unité Matériaux et Transformations, F-59000 Lille, FrancePolymeric scaffolds are promising in tissue engineering due to their structural similarity to extracellular matrix components. This study aimed to design freeze-dried hydrogels based on chitosan (CHT) and hyaluronic acid (HA). Chitosan-based gels were crosslinked with oxidized maltodextrin (MDo) before the freeze-drying step, resulting in spongy porous scaffolds. Based on the state-of-the-art, our hypothesis was that crosslinking would increase scaffold stiffness and delay the degradation of the CHT:HA resorbable scaffolds swelled in a hydrated physiological environment. The physicochemical and mechanical properties of crosslinked CHT- and CHT:HA-based scaffolds were analyzed. Hygroscopic and swelling behavior were assessed using dynamic vapor sorption analysis and batch studies. Degradation was evaluated under different conditions, including in phosphate-buffered saline (PBS), PBS with lysozyme, and lactic acid solutions, to investigate scaffold resistance against enzymatic and acidic degradation. The porosity of the spongy materials was characterized using scanning electron microscopy, while dynamic mechanical analysis provided information on the mechanical properties. Crosslinked scaffolds showed reduced swelling, slower degradation rates, and increased stiffness, confirming MDo as an effective crosslinking agent. Scaffolds loaded with ciprofloxacin (CFX) demonstrated their ability to deliver therapeutic agents, as the CFX loading capacity was promoted by CHT–CFX interactions. Microbiologic investigation confirmed the results. Finally, cytotoxicity tests displayed no toxicity. In conclusion, MDo-crosslinked CHT and CHT:HA scaffolds exhibit enhanced stability, functionality, and mechanical performance, making them promising for cartilage tissue engineering.https://www.mdpi.com/1420-3049/30/10/2202polymeric scaffoldschitosanhyaluronic acidcrosslinking hydrogelscartilage tissue engineeringporous morphology
spellingShingle Salim Hamidi
Mickael Maton
Feng Hildebrand
Valérie Gaucher
Cédric Bossard
Frédéric Cazaux
Jean Noel Staelens
Nicolas Blanchemain
Bernard Martel
Design and Evaluation of a Crosslinked Chitosan-Based Scaffold Containing Hyaluronic Acid for Articular Cartilage Reconstruction
Molecules
polymeric scaffolds
chitosan
hyaluronic acid
crosslinking hydrogels
cartilage tissue engineering
porous morphology
title Design and Evaluation of a Crosslinked Chitosan-Based Scaffold Containing Hyaluronic Acid for Articular Cartilage Reconstruction
title_full Design and Evaluation of a Crosslinked Chitosan-Based Scaffold Containing Hyaluronic Acid for Articular Cartilage Reconstruction
title_fullStr Design and Evaluation of a Crosslinked Chitosan-Based Scaffold Containing Hyaluronic Acid for Articular Cartilage Reconstruction
title_full_unstemmed Design and Evaluation of a Crosslinked Chitosan-Based Scaffold Containing Hyaluronic Acid for Articular Cartilage Reconstruction
title_short Design and Evaluation of a Crosslinked Chitosan-Based Scaffold Containing Hyaluronic Acid for Articular Cartilage Reconstruction
title_sort design and evaluation of a crosslinked chitosan based scaffold containing hyaluronic acid for articular cartilage reconstruction
topic polymeric scaffolds
chitosan
hyaluronic acid
crosslinking hydrogels
cartilage tissue engineering
porous morphology
url https://www.mdpi.com/1420-3049/30/10/2202
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