Immunoregenerative Microenvironment Modulation in Tendon-Ligament Regeneration: Evolution of Chitosan-Based Composite Biomaterials.
- 1Doctoral Program, Faculty of Medicine, Lambung Mangkurat University, Banjarbaru 70714, Indonesia.
- 2Department of Orthopaedics and Traumatology, Faculty of Medicine, Lambung Mangkurat University, Banjarmasin 70233, Indonesia.
- 3Department of Orthopaedics and Traumatology, Faculty of Medicine, Airlangga University, Surabaya 60286, Indonesia.
Abstract
Tendon and ligament injuries remain challenging to treat because healing may result in fibrosis, incomplete tendon-bone integration, impaired biomechanical properties, and reinjury. This review critically synthesizes preclinical evidence on chitosan-based composite biomaterials for tendon-ligament regeneration, focusing on their evolution from structural scaffolds toward multifunctional immunoregenerative platforms. Evidence across immune regulation, inflammatory signaling, angiogenesis, progenitor-cell activity, extracellular matrix remodeling, fibrocartilage formation, enthesis regeneration, tendon-bone healing, and biomechanical recovery was evaluated, while distinguishing direct chitosan-related evidence from contextual evidence derived from broader biomaterial systems. Chitosan-based platforms may support multiple regenerative domains through structural guidance, bioadhesion, localized delivery of bioactive components, and formulation-dependent immunomodulatory activity. However, heterogeneity in chitosan physicochemical properties, composite formulations, experimental models, and outcome measures limits direct comparison and prevents definitive attribution of multicomponent effects to chitosan alone. We propose the Immunoregenerative Cascade Theory and Immunoregenerative Tendon-Ligament Unit as complementary, hypothesis-generating frameworks for organizing temporal and spatial-functional interactions during regeneration. These frameworks are not validated causal or predictive models. Future research should prioritize standardized biomaterial characterization, longitudinal molecular-histological-biomechanical assessment, emerging multi-omics approaches, clinically relevant large-animal validation, and mechanism-guided biomaterial design to establish whether immunoregulatory effects translate into durable structural and functional tendon-ligament regeneration with long-term reproducible clinically meaningful recovery outcomes.
Related
- Breaking the degenerative triad: Microenvironment reprogramming biomaterials for intervertebral disc regeneration
- A 3D-printed composite scaffold with sequential delivery of QK and osteogenic growth peptides promotes diabetic bone regeneration through angiogenic and osteogenic modulation
- Therapeutic potential of natural product polysaccharides in hepatocellular carcinoma: from microenvironment modulation to combination strategies
- p38α orchestrates BRAFV600E-melanoma progression and immunotherapy response via tumor fitness and immune microenvironment modulation.
- Mechanistic insights on mogrosides as bifunctional regulators of metabolic reprogramming and immune modulation in tumor microenvironment
BibTeX
@article{ariyanto2026immunoregenerative,
title = {{Immunoregenerative Microenvironment Modulation in Tendon-Ligament Regeneration: Evolution of Chitosan-Based Composite Biomaterials.}},
author = {Muhammad Wibowo Ariyanto and Zairin Noor and Dwikora Novembri Utomo and Oski Illiandri},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198546},
url = {https://europepmc.org/article/MED/42883792},
note = {CC BY},
}
RIS
TY - JOUR
TI - Immunoregenerative Microenvironment Modulation in Tendon-Ligament Regeneration: Evolution of Chitosan-Based Composite Biomaterials.
AU - Muhammad Wibowo Ariyanto
AU - Zairin Noor
AU - Dwikora Novembri Utomo
AU - Oski Illiandri
PY - 2026
DA - 2026/09/24
JO - International journal of molecular sciences
DO - 10.3390/ijms27198546
UR - https://europepmc.org/article/MED/42883792
AB - Tendon and ligament injuries remain challenging to treat because healing may result in fibrosis, incomplete tendon-bone integration, impaired biomechanical properties, and reinjury. This review critically synthesizes preclinical evidence on chitosan-based composite biomaterials for tendon-ligament regeneration, focusing on their evolution from structural scaffolds toward multifunctional immunoregenerative platforms. Evidence across immune regulation, inflammatory signaling, angiogenesis, progenitor-cell activity, extracellular matrix remodeling, fibrocartilage formation, enthesis regeneration, tendon-bone healing, and biomechanical recovery was evaluated, while distinguishing direct chitosan-related evidence from contextual evidence derived from broader biomaterial systems. Chitosan-based platforms may support multiple regenerative domains through structural guidance, bioadhesion, localized delivery of bioactive components, and formulation-dependent immunomodulatory activity. However, heterogeneity in chitosan physicochemical properties, composite formulations, experimental models, and outcome measures limits direct comparison and prevents definitive attribution of multicomponent effects to chitosan alone. We propose the Immunoregenerative Cascade Theory and Immunoregenerative Tendon-Ligament Unit as complementary, hypothesis-generating frameworks for organizing temporal and spatial-functional interactions during regeneration. These frameworks are not validated causal or predictive models. Future research should prioritize standardized biomaterial characterization, longitudinal molecular-histological-biomechanical assessment, emerging multi-omics approaches, clinically relevant large-animal validation, and mechanism-guided biomaterial design to establish whether immunoregulatory effects translate into durable structural and functional tendon-ligament regeneration with long-term reproducible clinically meaningful recovery outcomes.
SN - 1422-0067
ER -