Injectable Trimethyl Chitosan Hydrogel with Capsaicin Mitigates Functional Pain and Angio-Osteogenic Coupling in an Animal Model of Osteoarthritis
7 affiliations
- 1Department of Orthopaedic Surgery, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Republic of Korea.
- 2Department of Orthopedic Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
- 3Beckman Laser Institute Korea, Dankook University College of Medicine, Cheonan, Republic of Korea.
- 4Dankook Institute of Medicine & Optics, Dankook University, Cheonan, Republic of Korea.
- 5Medical Laser Research Center, Dankook University, Cheonan, Republic of Korea.
- 6Department of Plastic and Reconstructive Surgery, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Republic of Korea.
- 7Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Republic of Korea.
Abstract
Osteoarthritis (OA) remains a leading cause of disability worldwide, with current therapies limited to symptomatic relief. In this study, we developed and evaluated a thermoresponsive hydrogel system based on N,N,N-trimethyl chitosan (TMC) for the sustained intra-articular delivery of capsaicin, an established analgesic. This study focused on assessing the system's biocompatibility, anti-inflammatory effects, and its impact on functional recovery in an animal model. A thermoresponsive hydrogel (1% TMC, 10% β-glycerophosphate) was formulated for stable gelation at 37 °C. Biocompatibility was assessed via cell count assays on rat articular chondrocytes and macrophages. Therapeutic impact was evaluated through rotarod performance and histological assessment of cartilage integrity in monoiodoacetate-induced OA in rats. Macrophage polarization was analyzed via immunofluorescence. In vitro, the TMC hydrogel successfully enhanced the biocompatibility of capsaicin while indicating a shift away from proinflammatory (M1) macrophage polarization, reflected in a 25% reduction of CD86⁺ cells while increasing CD206⁺ cells by 30%. Furthermore, this group exhibited consistent improvement in rotarod latency for up to 4 weeks post-treatment. Histopathological grading scores corroborated these functional improvements, with OA animal models treated with the TMC hydrogel loaded with capsaicin reaching only an average score of 2 compared to untreated control group's 6. Immunofluorescence analysis revealed marked reduction in angiogenic and interleukin-6 inflammatory markers compared to control groups. The TMC-capsaicin hydrogel system shows promise as a biocompatible localized injectable treatment for OA. This system was associated with improved functional performance and joint protection, along with reduced inflammatory marker expression and preservation of cartilage tissue integrity.
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BibTeX
@article{kim2026injectable,
title = {{Injectable Trimethyl Chitosan Hydrogel with Capsaicin Mitigates Functional Pain and Angio-Osteogenic Coupling in an Animal Model of Osteoarthritis}},
author = {Kyung Wook Kim and Andrew Reyes Padalhin and Hyun Seok Ryu and Celine Abueva and Jun Sang Bae and So Young Park and Hong Bae Jeon and Ji-Hun Mo and Phil-Sang Chung and Hyun Sik Gong and Seung Hoon Woo},
journal = {Biomaterials research},
year = {2026},
month = oct,
doi = {10.34133/bmr.0424},
url = {https://europepmc.org/article/PMC/PMC13716988},
note = {CC BY},
}
RIS
TY - JOUR
TI - Injectable Trimethyl Chitosan Hydrogel with Capsaicin Mitigates Functional Pain and Angio-Osteogenic Coupling in an Animal Model of Osteoarthritis
AU - Kyung Wook Kim
AU - Andrew Reyes Padalhin
AU - Hyun Seok Ryu
AU - Celine Abueva
AU - Jun Sang Bae
AU - So Young Park
AU - Hong Bae Jeon
AU - Ji-Hun Mo
AU - Phil-Sang Chung
AU - Hyun Sik Gong
AU - Seung Hoon Woo
PY - 2026
DA - 2026/10/29
JO - Biomaterials research
DO - 10.34133/bmr.0424
UR - https://europepmc.org/article/PMC/PMC13716988
AB - Osteoarthritis (OA) remains a leading cause of disability worldwide, with current therapies limited to symptomatic relief. In this study, we developed and evaluated a thermoresponsive hydrogel system based on N,N,N-trimethyl chitosan (TMC) for the sustained intra-articular delivery of capsaicin, an established analgesic. This study focused on assessing the system's biocompatibility, anti-inflammatory effects, and its impact on functional recovery in an animal model. A thermoresponsive hydrogel (1% TMC, 10% β-glycerophosphate) was formulated for stable gelation at 37 °C. Biocompatibility was assessed via cell count assays on rat articular chondrocytes and macrophages. Therapeutic impact was evaluated through rotarod performance and histological assessment of cartilage integrity in monoiodoacetate-induced OA in rats. Macrophage polarization was analyzed via immunofluorescence. In vitro, the TMC hydrogel successfully enhanced the biocompatibility of capsaicin while indicating a shift away from proinflammatory (M1) macrophage polarization, reflected in a 25% reduction of CD86⁺ cells while increasing CD206⁺ cells by 30%. Furthermore, this group exhibited consistent improvement in rotarod latency for up to 4 weeks post-treatment. Histopathological grading scores corroborated these functional improvements, with OA animal models treated with the TMC hydrogel loaded with capsaicin reaching only an average score of 2 compared to untreated control group's 6. Immunofluorescence analysis revealed marked reduction in angiogenic and interleukin-6 inflammatory markers compared to control groups. The TMC-capsaicin hydrogel system shows promise as a biocompatible localized injectable treatment for OA. This system was associated with improved functional performance and joint protection, along with reduced inflammatory marker expression and preservation of cartilage tissue integrity.
SN - 1226-4601
SN - 2055-7124
ER -