Overcoming Intra-Articular Delivery Barriers in Cartilage Regeneration: Emerging Controlled-Release Strategies
- 1Department of Surgery, Division of Surgical and Interventional Sciences, McGill University, Montreal, QC H3G 1A4, Canada
- 2Orthopaedic Research Laboratory, Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montreal, QC H3T 1E2, Canada
Abstract
Articular cartilage has a limited capacity for self-repair due to its avascular nature, dense extracellular matrix, and low cellularity. Current treatments for cartilage injury and osteoarthritis (OA) often provide temporary symptom relief but do not restore native tissue structure or function. Intra-articular (IA) administration enables localized delivery of therapeutic agents; however, its effectiveness is limited by rapid clearance from the joint, poor cartilage penetration, and insufficient tissue retention. Controlled-release systems, including scaffolds, hydrogels, nanoparticles, and stimuli-responsive platforms, have been developed to address these barriers by prolonging local therapeutic exposure and enabling sustained or targeted delivery. Preclinical studies have demonstrated the potential of these systems to reduce inflammation and support cartilage protection and repair. However, clinical evidence remains limited, and further studies are required to determine whether these delivery advantages translate into sustained disease-modifying or regenerative outcomes in patients. This review discusses the biological barriers that limit effective IA delivery and summarizes recent advances in controlled-release strategies, with particular attention to their ability to improve joint retention, cartilage penetration, and sustained therapeutic exposure. The advantages and limitations of the different delivery platforms are critically discussed, together with the translational challenges that currently limit their progression from preclinical studies to clinical application.
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BibTeX
@article{yousef2026overcoming,
title = {{Overcoming Intra-Articular Delivery Barriers in Cartilage Regeneration: Emerging Controlled-Release Strategies}},
author = {Fajer Yousef and Muskan Alad and Laura M. Epure and Angelina Lui and Michael P. Grant and Nicoletta Eliopoulos and John Antoniou and Fackson Mwale},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101457},
url = {https://www.mdpi.com/2218-273X/16/10/1457},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Overcoming Intra-Articular Delivery Barriers in Cartilage Regeneration: Emerging Controlled-Release Strategies
AU - Fajer Yousef
AU - Muskan Alad
AU - Laura M. Epure
AU - Angelina Lui
AU - Michael P. Grant
AU - Nicoletta Eliopoulos
AU - John Antoniou
AU - Fackson Mwale
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101457
UR - https://www.mdpi.com/2218-273X/16/10/1457
AB - Articular cartilage has a limited capacity for self-repair due to its avascular nature, dense extracellular matrix, and low cellularity. Current treatments for cartilage injury and osteoarthritis (OA) often provide temporary symptom relief but do not restore native tissue structure or function. Intra-articular (IA) administration enables localized delivery of therapeutic agents; however, its effectiveness is limited by rapid clearance from the joint, poor cartilage penetration, and insufficient tissue retention. Controlled-release systems, including scaffolds, hydrogels, nanoparticles, and stimuli-responsive platforms, have been developed to address these barriers by prolonging local therapeutic exposure and enabling sustained or targeted delivery. Preclinical studies have demonstrated the potential of these systems to reduce inflammation and support cartilage protection and repair. However, clinical evidence remains limited, and further studies are required to determine whether these delivery advantages translate into sustained disease-modifying or regenerative outcomes in patients. This review discusses the biological barriers that limit effective IA delivery and summarizes recent advances in controlled-release strategies, with particular attention to their ability to improve joint retention, cartilage penetration, and sustained therapeutic exposure. The advantages and limitations of the different delivery platforms are critically discussed, together with the translational challenges that currently limit their progression from preclinical studies to clinical application.
SN - 2218-273X
ER -