Cartilage repair remains a significant challenge in orthopedics due to the limited self-healing capacity of articular cartilage, with conventional treatments for osteoarthritis and other joint diseases often yielding suboptimal outcomes. This review highlights a groundbreaking study published in International Journal of Biological Macromolecules, exploring the role of modified citrus pectin (MCP) in 3D printing-based cartilage tissue engineering. By integrating MCP into bioinks and 3D-printed scaffolds, researchers demonstrate its potential to enhance chondrocyte proliferation, maintain cellular phenotype, and modulate key molecular pathways, offering a promising paradigm for cartilage regeneration.
The Unmet Need in Cartilage Repair
Arthritis and joint injuries affect millions worldwide, imposing substantial physical and socioeconomic burdens. Central to these challenges is the intrinsic inability of articular cartilage to regenerate, as its avascular nature and low cellularity hinder natural healing. Traditional interventions, such as microfracture and autologous chondrocyte implantation, often fail to restore functional cartilage, necessitating innovative strategies. Cartilage tissue engineering—combining biomaterials, cells, and scaffolds—has emerged as a transformative approach, with 3D printing offering unprecedented precision in creating anatomically tailored constructs.
Against this backdrop, a recent study by Su et al. (2025) delves into the therapeutic potential of modified citrus pectin (MCP), a low-molecular-weight, low-esterified polysaccharide with FDA GRAS status. Renowned for its anti-inflammatory, antifibrotic, and immunomodulatory properties via galectin-3 (Gal-3) binding, MCP has shown promise in preclinical models of cartilage injury. However, its mechanism of action and applicability in 3D bioprinting remain underexplored.
Key Findings: MCP’s Multifaceted Role in Cartilage Regeneration
Using a rabbit knee cartilage defect model, researchers first validated MCP’s protective effects. While full defect resolution was not achieved, MCP treatment dose-dependently preserved chondrocytes and enhanced glycosaminoglycan (GAG) deposition compared to controls. Mechanistically, fluorescently labeled MCP penetrated cartilage tissue within 24 hours, accumulating in chondrocyte lysosomes and co-localizing with Gal-3. Notably, MCP reduced injury-induced chondrocyte apoptosis without affecting basal proliferation but significantly boosted proliferation in passaged chondrocytes, with up to 5-fold higher rates in late passages (6–7) versus controls.
Figure 1: Effects of modified citrus pectin (MCP) on partial thickness articular cartilage (AC) defects
MCP also mitigated chondrocyte dedifferentiation, maintaining polygonal morphology and upregulating cartilage-specific genes (COL2A1, SOX9) while suppressing Gal-3 and IL-1β expression. These effects underscore MCP’s dual role in promoting cellular viability and preserving phenotypic stability.
Figure 2: Effects of MCP on proliferation and gene expression of chondrocytes in continuous culture from the 2nd to the 8th generation
To translate these findings into tissue engineering, MCP was integrated into GelMA/HAMA (gelatin methacryloyl/hyaluronic acid methacryloyl) bioinks. Rheological analyses revealed shear-thinning behavior suitable for 3D printing, with temperature-responsive viscosity transitions (high at ≤27°C, sol-like at ~36°C) and favorable viscoelastic properties (G’ > G’’), ensuring structural integrity during printing.
The resulting 3D-printed scaffolds exhibited ~500-μm porous architectures ideal for cell infiltration, confirmed by scanning electron microscopy. Fourier transform infrared spectroscopy validated MCP incorporation, while compression tests showed mechanical properties within the physiological range for cartilage, despite reduced modulus with higher MCP content. Swelling ratios and degradation rates increased with MCP loading, with ~85% degradation over 5 days, and sustained release kinetics featuring an initial burst followed by gradual dissipation.
In vitro studies confirmed the scaffolds’ cytocompatibility and robust chondroproliferative effects. Transcriptomic analysis revealed MCP-driven upregulation of pathways linked to cartilage formation and autophagy, alongside downregulation of inflammatory and catabolic genes (e.g., Gal-3, MMP13). Histological and immunofluorescent staining further demonstrated enhanced chondrocyte density and type II collagen deposition in GelMA/HAMA/MCP scaffolds versus controls, highlighting their superior regenerative potential.
Figure 4: Schematic diagram of the potential mechanism of MCP in tissue engineering cartilage construction and articular cartilage defect repair
Conclusion: Bridging Bench to Bedside
This study establishes MCP as a versatile biomaterial in 3D printing for cartilage repair, combining anti-inflammatory actions, chondroprotective effects, and scaffold-enhancing properties. By modulating Gal-3 signaling and promoting functional matrix synthesis, MCP-based constructs offer a holistic approach to addressing cartilage degeneration. While preclinical success is promising, translating these findings to clinical use requires rigorous validation in larger animal models, optimization of dosing strategies, and long-term safety assessments.
As 3D bioprinting continues to revolutionize regenerative medicine, the integration of natural polymers like MCP could pave the way for personalized, off-the-shelf cartilage repair solutions, ultimately restoring mobility and quality of life for millions affected by joint disease.
