Self-healing injectable N-succinyl chitosan-hyaluronic dialdehyde hydrogel with chitosan-coated poly(D,l-lactide-co-glycolide) nanoparticles for kartogenin loading

Paveena Tikakosol; Paul D. Topham; Matthew J. Derry; Runglawan Somsunan; Patnarin Worajittiphon; Chawan Manaspon; Winita Punyodom

doi:10.1016/j.ijbiomac.2026.151062

Self-healing injectable N-succinyl chitosan-hyaluronic dialdehyde hydrogel with chitosan-coated poly(D,l-lactide-co-glycolide) nanoparticles for kartogenin loading

Paveena Tikakosol
, Paul D. Topham
, Matthew J. Derry
, Runglawan Somsunan
, Patnarin Worajittiphon
, Chawan Manaspon
, Winita Punyodom^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Sustained intra-articular delivery is crucial for effective osteoarthritis (OA) therapy. We developed a dual-encapsulation platform by embedding kartogenin (KGN)-loaded chitosan-coated PLGA nanoparticles (PLGA-CS NPs) into a self-healing N-succinyl chitosan (NSC)-hyaluronic dialdehyde (HAD) hydrogel. Chitosan coating reversed the zeta potential of the NPs from −23.1 mV to +35.4 mV, enhancing electrostatic affinity for anionic cartilage. The NSC–HAD hydrogel rapidly gelled via Schiff-base linkages, maintained injectability, and retained self-healing capabilities following NPs incorporation. Rheology showed shear-thinning behavior; PLGA NPs increased the flow point (τf), whereas PLGA-CS NPs decreased τf via stronger physical interactions. Hydrogels exhibited 60–80% recovery of G′ after undergoing 1000% strain. KGN release reached ∼70% in 3 h from uncoated PLGA NPs, ∼40% with CS coating, and ∼ 18% over 28 days when embedded in hydrogel. The composite hydrogel exhibited high biocompatibility and supported mMSC viability in vitro. Based on the established release kinetics and structural integrity, this platform provides a tunable framework for sustained intra-articular drug delivery. This work serves as a physicochemical foundation for future biological studies aimed at evaluating its therapeutic retention and regenerative potential in osteoarthritis models.

Original language	English
Article number	151062
Number of pages	16
Journal	International Journal of Biological Macromolecules
Volume	353
Early online date	24 Feb 2026
DOIs	https://doi.org/10.1016/j.ijbiomac.2026.151062
Publication status	Published - Apr 2026

Bibliographical note

Copyright © 2026, Published by Elsevier B.V.. This accepted manuscript version is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International https://creativecommons.org/licenses/by-nc-nd/4.0/

Funding

This research project was supported by the Fundamental Fund, Chiang Mai University , and Thailand Science Research and Innovation (TSRI) , as well as the Hub of Talents in Bioplastics for Use in Medical Applications (BioMED HUB). Researcher-exchange support was provided through the European Union's Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie Grant Agreement No. 871650 (MEDIPOL). The Aston Institute for Membrane Excellence (AIME) is funded by UKRI Research England under the Expanding Excellence in England (E3) scheme. P. Tikakosol gratefully acknowledges the Science Achievement Scholarship of Thailand (SAST) for graduate funding.

Funders	Funder number
Thailand Science Research and Innovation
Science Achievement Scholarship of Thailand
UK Research and Innovation
Chiang Mai University
Horizon 2020 Framework Programme	871650

Keywords

Self-healing hydrogel
Nanoparticles
Drug delivery
Dual-encapsulation
Injectable hydrogel

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10.1016/j.ijbiomac.2026.151062

Cite this

Tikakosol, P., Topham, P. D., Derry, M. J., Somsunan, R., Worajittiphon, P., Manaspon, C., & Punyodom, W. (2026). Self-healing injectable N-succinyl chitosan-hyaluronic dialdehyde hydrogel with chitosan-coated poly(D,l-lactide-co-glycolide) nanoparticles for kartogenin loading. International Journal of Biological Macromolecules, 353, Article 151062. https://doi.org/10.1016/j.ijbiomac.2026.151062

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abstract = "Sustained intra-articular delivery is crucial for effective osteoarthritis (OA) therapy. We developed a dual-encapsulation platform by embedding kartogenin (KGN)-loaded chitosan-coated PLGA nanoparticles (PLGA-CS NPs) into a self-healing N-succinyl chitosan (NSC)-hyaluronic dialdehyde (HAD) hydrogel. Chitosan coating reversed the zeta potential of the NPs from −23.1 mV to +35.4 mV, enhancing electrostatic affinity for anionic cartilage. The NSC–HAD hydrogel rapidly gelled via Schiff-base linkages, maintained injectability, and retained self-healing capabilities following NPs incorporation. Rheology showed shear-thinning behavior; PLGA NPs increased the flow point (τf), whereas PLGA-CS NPs decreased τf via stronger physical interactions. Hydrogels exhibited 60–80\% recovery of G′ after undergoing 1000\% strain. KGN release reached ∼70\% in 3 h from uncoated PLGA NPs, ∼40\% with CS coating, and ∼ 18\% over 28 days when embedded in hydrogel. The composite hydrogel exhibited high biocompatibility and supported mMSC viability in vitro. Based on the established release kinetics and structural integrity, this platform provides a tunable framework for sustained intra-articular drug delivery. This work serves as a physicochemical foundation for future biological studies aimed at evaluating its therapeutic retention and regenerative potential in osteoarthritis models.",

keywords = "Self-healing hydrogel, Nanoparticles, Drug delivery, Dual-encapsulation, Injectable hydrogel",

author = "Paveena Tikakosol and Topham, \{Paul D.\} and Derry, \{Matthew J.\} and Runglawan Somsunan and Patnarin Worajittiphon and Chawan Manaspon and Winita Punyodom",

note = "Copyright {\textcopyright} 2026, Published by Elsevier B.V.. This accepted manuscript version is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International https://creativecommons.org/licenses/by-nc-nd/4.0/",

year = "2026",

month = apr,

doi = "10.1016/j.ijbiomac.2026.151062",

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Tikakosol, P, Topham, PD , Derry, MJ, Somsunan, R, Worajittiphon, P, Manaspon, C & Punyodom, W 2026, 'Self-healing injectable N-succinyl chitosan-hyaluronic dialdehyde hydrogel with chitosan-coated poly(D,l-lactide-co-glycolide) nanoparticles for kartogenin loading', International Journal of Biological Macromolecules, vol. 353, 151062. https://doi.org/10.1016/j.ijbiomac.2026.151062

Self-healing injectable N-succinyl chitosan-hyaluronic dialdehyde hydrogel with chitosan-coated poly(D,l-lactide-co-glycolide) nanoparticles for kartogenin loading. / Tikakosol, Paveena; Topham, Paul D.; Derry, Matthew J. et al.
In: International Journal of Biological Macromolecules, Vol. 353, 151062, 04.2026.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Self-healing injectable N-succinyl chitosan-hyaluronic dialdehyde hydrogel with chitosan-coated poly(D,l-lactide-co-glycolide) nanoparticles for kartogenin loading

AU - Tikakosol, Paveena

AU - Topham, Paul D.

AU - Derry, Matthew J.

AU - Somsunan, Runglawan

AU - Worajittiphon, Patnarin

AU - Manaspon, Chawan

AU - Punyodom, Winita

N1 - Copyright © 2026, Published by Elsevier B.V.. This accepted manuscript version is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International https://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2026/4

Y1 - 2026/4

N2 - Sustained intra-articular delivery is crucial for effective osteoarthritis (OA) therapy. We developed a dual-encapsulation platform by embedding kartogenin (KGN)-loaded chitosan-coated PLGA nanoparticles (PLGA-CS NPs) into a self-healing N-succinyl chitosan (NSC)-hyaluronic dialdehyde (HAD) hydrogel. Chitosan coating reversed the zeta potential of the NPs from −23.1 mV to +35.4 mV, enhancing electrostatic affinity for anionic cartilage. The NSC–HAD hydrogel rapidly gelled via Schiff-base linkages, maintained injectability, and retained self-healing capabilities following NPs incorporation. Rheology showed shear-thinning behavior; PLGA NPs increased the flow point (τf), whereas PLGA-CS NPs decreased τf via stronger physical interactions. Hydrogels exhibited 60–80% recovery of G′ after undergoing 1000% strain. KGN release reached ∼70% in 3 h from uncoated PLGA NPs, ∼40% with CS coating, and ∼ 18% over 28 days when embedded in hydrogel. The composite hydrogel exhibited high biocompatibility and supported mMSC viability in vitro. Based on the established release kinetics and structural integrity, this platform provides a tunable framework for sustained intra-articular drug delivery. This work serves as a physicochemical foundation for future biological studies aimed at evaluating its therapeutic retention and regenerative potential in osteoarthritis models.

AB - Sustained intra-articular delivery is crucial for effective osteoarthritis (OA) therapy. We developed a dual-encapsulation platform by embedding kartogenin (KGN)-loaded chitosan-coated PLGA nanoparticles (PLGA-CS NPs) into a self-healing N-succinyl chitosan (NSC)-hyaluronic dialdehyde (HAD) hydrogel. Chitosan coating reversed the zeta potential of the NPs from −23.1 mV to +35.4 mV, enhancing electrostatic affinity for anionic cartilage. The NSC–HAD hydrogel rapidly gelled via Schiff-base linkages, maintained injectability, and retained self-healing capabilities following NPs incorporation. Rheology showed shear-thinning behavior; PLGA NPs increased the flow point (τf), whereas PLGA-CS NPs decreased τf via stronger physical interactions. Hydrogels exhibited 60–80% recovery of G′ after undergoing 1000% strain. KGN release reached ∼70% in 3 h from uncoated PLGA NPs, ∼40% with CS coating, and ∼ 18% over 28 days when embedded in hydrogel. The composite hydrogel exhibited high biocompatibility and supported mMSC viability in vitro. Based on the established release kinetics and structural integrity, this platform provides a tunable framework for sustained intra-articular drug delivery. This work serves as a physicochemical foundation for future biological studies aimed at evaluating its therapeutic retention and regenerative potential in osteoarthritis models.

KW - Self-healing hydrogel

KW - Nanoparticles

KW - Drug delivery

KW - Dual-encapsulation

KW - Injectable hydrogel

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UR - https://www.scopus.com/pages/publications/105034268537

U2 - 10.1016/j.ijbiomac.2026.151062

DO - 10.1016/j.ijbiomac.2026.151062

M3 - Article

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JO - International Journal of Biological Macromolecules

JF - International Journal of Biological Macromolecules

M1 - 151062

ER -

Tikakosol P, Topham PD , Derry MJ, Somsunan R, Worajittiphon P, Manaspon C et al. Self-healing injectable N-succinyl chitosan-hyaluronic dialdehyde hydrogel with chitosan-coated poly(D,l-lactide-co-glycolide) nanoparticles for kartogenin loading. International Journal of Biological Macromolecules. 2026 Apr;353:151062. Epub 2026 Feb 24. doi: 10.1016/j.ijbiomac.2026.151062

Self-healing injectable N-succinyl chitosan-hyaluronic dialdehyde hydrogel with chitosan-coated poly(D,l-lactide-co-glycolide) nanoparticles for kartogenin loading

Abstract

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Keywords

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