A thermo-responsive chitosan-based injectable hydrogel for delivery of curcumin-loaded polycaprolactone microspheres to articular cartilage: in-vitro and in-vivo assessments

Articular cartilage has limited regenerative capacity, posing a significant challenge in healing cartilage-related disorders. While injectable hydrogels have shown potential as a treatment, achieving an optimal balance between bio-compatibility, mechanical properties, and drug delivery remains a cha...

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Main Authors: Farnoosh Kalantarnia, Sasan Maleki, Amir Shamloo, Kazem Akbarnataj, Sayed Navid Tavoosi
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Carbohydrate Polymer Technologies and Applications
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666893925000180
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author Farnoosh Kalantarnia
Sasan Maleki
Amir Shamloo
Kazem Akbarnataj
Sayed Navid Tavoosi
author_facet Farnoosh Kalantarnia
Sasan Maleki
Amir Shamloo
Kazem Akbarnataj
Sayed Navid Tavoosi
author_sort Farnoosh Kalantarnia
collection DOAJ
description Articular cartilage has limited regenerative capacity, posing a significant challenge in healing cartilage-related disorders. While injectable hydrogels have shown potential as a treatment, achieving an optimal balance between bio-compatibility, mechanical properties, and drug delivery remains a challenge. This study developed a chitosan-based injectable hydrogel reinforced with bacterial cellulose nanofibers to enhance mechanical stability and biological functionality. The hydrogel exhibited great porosity (∼57.96 %) with a mean pore diameter of ∼104.30 µm, and a compressive modulus of ∼4.65 kPa, offering an encouraging micro-environment for cell proliferation and tissue regeneration. The degradation rate of ∼55 % over 30 days was tailored to match the timeline of cartilage repair. Additionally, polycaprolactone microspheres, prepared by solid/oil/water method, were used to enhance the bio-availability of curcumin and its sustained delivery. The hydrogel system containing drug-loaded microspheres showed ∼23.55 % drug released by day 7. Moreover, anti-bacterial assays confirmed the hydrogel's effectiveness against S. aureus and E. coli. Also, bio-compatibility assessments showed high fibroblast viability over 7 days. In-vivo evaluations on rabbit models indicated significant cartilage regeneration, evidenced by improved locomotion behavior and accelerated cartilage formation with minimized defect boundaries. Similarly, histological analysis revealed enhanced chondrocyte density compared to the control group. These findings highlight the synergistic role of scaffold composition, mechanical properties, and controlled drug delivery in promoting cartilage regeneration, underscoring the potential clinical applications of this multifaceted hydrogel for cartilage repair.
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spelling doaj-art-e953f227b68b452284c1fde14930a6c12025-02-02T05:29:27ZengElsevierCarbohydrate Polymer Technologies and Applications2666-89392025-03-019100678A thermo-responsive chitosan-based injectable hydrogel for delivery of curcumin-loaded polycaprolactone microspheres to articular cartilage: in-vitro and in-vivo assessmentsFarnoosh Kalantarnia0Sasan Maleki1Amir Shamloo2Kazem Akbarnataj3Sayed Navid Tavoosi4Department of Mechanical Engineering, Sharif University of Technology, Tehran, IranDepartment of Mechanical Engineering, Sharif University of Technology, Tehran, Iran; Stem Cell and Regenerative Medicine Institute, Sharif University of Technology, Tehran, IranDepartment of Mechanical Engineering, Sharif University of Technology, Tehran, Iran; Stem Cell and Regenerative Medicine Institute, Sharif University of Technology, Tehran, Iran; Correspondence author at: School of Mechanical Engineering, Sharif University of Technology, Azadi Ave., Tehran, Iran.Department of Mechanical Engineering, Isfahan University of Technology, Isfahan, IranDepartment of Mechanical Engineering, Sharif University of Technology, Tehran, Iran; Stem Cell and Regenerative Medicine Institute, Sharif University of Technology, Tehran, IranArticular cartilage has limited regenerative capacity, posing a significant challenge in healing cartilage-related disorders. While injectable hydrogels have shown potential as a treatment, achieving an optimal balance between bio-compatibility, mechanical properties, and drug delivery remains a challenge. This study developed a chitosan-based injectable hydrogel reinforced with bacterial cellulose nanofibers to enhance mechanical stability and biological functionality. The hydrogel exhibited great porosity (∼57.96 %) with a mean pore diameter of ∼104.30 µm, and a compressive modulus of ∼4.65 kPa, offering an encouraging micro-environment for cell proliferation and tissue regeneration. The degradation rate of ∼55 % over 30 days was tailored to match the timeline of cartilage repair. Additionally, polycaprolactone microspheres, prepared by solid/oil/water method, were used to enhance the bio-availability of curcumin and its sustained delivery. The hydrogel system containing drug-loaded microspheres showed ∼23.55 % drug released by day 7. Moreover, anti-bacterial assays confirmed the hydrogel's effectiveness against S. aureus and E. coli. Also, bio-compatibility assessments showed high fibroblast viability over 7 days. In-vivo evaluations on rabbit models indicated significant cartilage regeneration, evidenced by improved locomotion behavior and accelerated cartilage formation with minimized defect boundaries. Similarly, histological analysis revealed enhanced chondrocyte density compared to the control group. These findings highlight the synergistic role of scaffold composition, mechanical properties, and controlled drug delivery in promoting cartilage regeneration, underscoring the potential clinical applications of this multifaceted hydrogel for cartilage repair.http://www.sciencedirect.com/science/article/pii/S2666893925000180Thermo-responsive hydrogelTissue engineeringCurcuminMicrospheres
spellingShingle Farnoosh Kalantarnia
Sasan Maleki
Amir Shamloo
Kazem Akbarnataj
Sayed Navid Tavoosi
A thermo-responsive chitosan-based injectable hydrogel for delivery of curcumin-loaded polycaprolactone microspheres to articular cartilage: in-vitro and in-vivo assessments
Carbohydrate Polymer Technologies and Applications
Thermo-responsive hydrogel
Tissue engineering
Curcumin
Microspheres
title A thermo-responsive chitosan-based injectable hydrogel for delivery of curcumin-loaded polycaprolactone microspheres to articular cartilage: in-vitro and in-vivo assessments
title_full A thermo-responsive chitosan-based injectable hydrogel for delivery of curcumin-loaded polycaprolactone microspheres to articular cartilage: in-vitro and in-vivo assessments
title_fullStr A thermo-responsive chitosan-based injectable hydrogel for delivery of curcumin-loaded polycaprolactone microspheres to articular cartilage: in-vitro and in-vivo assessments
title_full_unstemmed A thermo-responsive chitosan-based injectable hydrogel for delivery of curcumin-loaded polycaprolactone microspheres to articular cartilage: in-vitro and in-vivo assessments
title_short A thermo-responsive chitosan-based injectable hydrogel for delivery of curcumin-loaded polycaprolactone microspheres to articular cartilage: in-vitro and in-vivo assessments
title_sort thermo responsive chitosan based injectable hydrogel for delivery of curcumin loaded polycaprolactone microspheres to articular cartilage in vitro and in vivo assessments
topic Thermo-responsive hydrogel
Tissue engineering
Curcumin
Microspheres
url http://www.sciencedirect.com/science/article/pii/S2666893925000180
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