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Osteoarthritis (OA) is a chronic joint disease characterized by progressive degeneration and wear of the joint cartilage, leading to increased mechanical friction, synovial inflammation, and irreversible pathological changes. Therefore, enhancing lubrication at the site of cartilage damage and inhibiting inflammation is an effective strategy for treating OA. This study was inspired by the hydration lubrication mechanism of healthy joint cartilage and the exposure of amino groups related to cartilage degeneration. Through the modification of bimodal ionic polymer poly(2-methylacryloyloxyethyl phosphocholine) (PMPC) and aldehyde groups on the surface of biodegradable mesoporous silica nanoparticles (bMSNs), a triple-functional nanosphere (bMSNs@MPC-HBA) was developed. Physical and chemical characterization, in vitro tribology and cell experiments, as well as in vivo animal studies all demonstrated that after pre-loading anti-inflammatory drugs, this nanosphere exhibited enhanced lubrication performance, cartilage-targeted drug delivery, and anti-inflammatory effects. These properties help protect damaged joint cartilage, regulate the joint microenvironment, and improve therapeutic efficacy in OA models. Additionally, this nanosphere shows good biocompatibility and significantly reduces macrophage uptake after intra-articular injection. These multifunctional nanospheres with enhanced lubrication and sustained drug release capabilities represent a promising biomaterial for targeted OA treatment.
Figure 1. Schematic diagram of the synthesis and application of the triple-functional nanosphere (bMSNs@MPC-HBA@DS) designed to enhance lubrication, target drug delivery to damaged cartilage, and exhibit anti-inflammatory effects. Enhanced lubrication is achieved through the hydration lubrication mechanism of the bimodal ionic polymer (PMPC). Targeting is mediated by the aldehyde groups on the nanosphere (−CHO) reacting with the amino groups (−NH₂) exposed on the damaged joint cartilage surface. Anti-inflammatory activity is achieved by the sustained release of the encapsulated drug (DS) at the target site.
[Research Background]
Osteoarthritis (OA) is a chronic joint disease affecting over 650 million people worldwide. The core pathologies include:
Lubrication failure: Degeneration of joint cartilage leads to a reduction in bio-lubricants (such as hyaluronic acid), resulting in a significant increase in the friction coefficient (COF) (healthy joint COF ≈ 0.001, significantly increased in OA joints);
Inflammatory cascade: Mechanical wear releases collagen fragments, triggering a pro-inflammatory factor storm, accelerating cartilage matrix degradation;
Targeting difficulty: Traditional oral anti-inflammatory drugs have a systemic distribution that easily leads to drug resistance, and intra-articular injection of hyaluronic acid is prone to enzymatic degradation and requires repeated punctures, with high complication risks.
Current therapies cannot simultaneously address the issues of lubrication, targeting, and anti-inflammatory effects, and thus a multifunctional integrated strategy is urgently needed.
[Innovations and Highlights]
This study designed the bMSNs@MPC-HBA@DS nanosphere, which achieves the synergistic functions of three elements through the biomimetic "hydration lubrication" mechanism of the healthy joint cartilage:
1. Enhanced hydration lubrication
Biomimetic design: Surface grafting of bimodal ionic polymer PMPC (poly(methylacryloyloxyethyl phosphocholine)), with the phosphocholine groups (-N⁺(CH₃)₃ / -PO₄⁻) forming sub-nanometer-sized hydration layers, maintaining ultra-low friction (COF = 0.026, 85% lower than unmodified nanospheres under high shear);
Newtonian fluid properties: The suspension of the nanosphere has stable viscosity, suitable for dynamic joint environments.
2. Precise targeting of damaged cartilage
Intelligent anchoring: Surface aldehyde groups (−CHO) specifically bind to the amino groups (−NH₂) exposed on the OA cartilage surface through the Schiff base reaction, with a 4-fold higher targeting efficiency compared to non-targeted nanospheres (verified in vitro/ in vitro experiments);
Microenvironment response: The acidic OA joint microenvironment (pH ≈ 6.0) accelerates nanosphere degradation, promoting targeted drug release.
3. Integrated anti-inflammatory-immune regulation
Drug loading optimization: Mesoporous silica nanospheres (bMSNs) loaded with diclofenac sodium (DS), with the PMPC shell enhancing the drug loading rate (LC = 12.97%, EE = 88.09%);
Immune evasion: The hydrated layer of PMPC reduces protein adsorption, and the macrophage uptake rate decreases by 80%, prolonging the retention time in the joint cavity;
Regulation of inflammation: Sustained-release of DS downregulates the expression of TNF-α/IL-6/IL-1β and promotes the polarization of macrophages towards the anti-inflammatory M2 type (M2 proportion: 86.9% vs 0.79%).
Original link：https://doi.org/10.1002/adfm.202501235
