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. 2024 Feb 22:25:100993.
doi: 10.1016/j.mtbio.2024.100993. eCollection 2024 Apr.

Injectable nanocomposite hydrogels with enhanced lubrication and antioxidant properties for the treatment of osteoarthritis

Qizhu Chen  1 , Yuxin Jin  1 , Tao Chen  2 , Hao Zhou  1 , Xinzhou Wang  1 , Ouqiang Wu  1 , Linjie Chen  1 , Zhiguang Zhang  1 , Zhengyu Guo  1 , Jin Sun  1 , Aimin Wu  1 , Qiuping Qian  3
Affiliations

Injectable nanocomposite hydrogels with enhanced lubrication and antioxidant properties for the treatment of osteoarthritis

Qizhu Chen et al. Mater Today Bio. .

Abstract

Osteoarthritis (OA) is a chronic inflammatory joint disease characterized by progressive cartilage degeneration, synovitis, and osteoid formation. In order to effectively treat OA, it is important to block the harmful feedback caused by reactive oxygen species (ROS) produced during joint wear. To address this challenge, we have developed injectable nanocomposite hydrogels composed of polygallate-Mn (PGA-Mn) nanoparticles, oxidized sodium alginate, and gelatin. The inclusion of PGA-Mn not only enhances the mechanical strength of the biohydrogel through a Schiff base reaction with gelatin but also ensures efficient ROS scavenging ability. Importantly, the nanocomposite hydrogel exhibits excellent biocompatibility, allowing it to effectively remove ROS from chondrocytes and reduce the expression of inflammatory factors within the joint. Additionally, the hygroscopic properties of the hydrogel contribute to reduced intra-articular friction and promote the production of cartilage-related proteins, supporting cartilage synthesis. In vivo experiments involving the injection of nanocomposite hydrogels into rat knee joints with an OA model have demonstrated successful reduction of osteophyte formation and protection of cartilage from wear, highlighting the therapeutic potential of this approach for treating OA.

Keywords: Anti-inflammatory; Extracellular; Gelatin; Matrix; Osteoarthritis; Oxidized alginate.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Scheme 1
Scheme 1
Preparation and action process of nanocomposite hydrogels.
Fig. 1
Fig. 1
Characterization of PGA-Mn and OGPGM. (A) SEM image of the PGA-Mn. (B) Size distribution liposomes. (C) Full scan XPS survey spectrum and the high-resolution spectra of PGA-Mn for (D) C1s (E) O1s (F) and Mn2p. (G) ATR-FTIR analysis of the chemical structures of OGPGM. (H) SEM images of OGPGM. (I) Elemental mapping images of OGPGM (J, K) The homogeneous distribution of red fluorescence from cy5.5-labeled PGA-Mn in the OGPGM.
Fig. 2
Fig. 2
The material properties of the OGPGM. (A) The hygroscopicity of OG, OGPGM(1:5) and OGPGM(1:10) (n = 3). (B) COF–time plots and (C) COF histograms for PBS, OG, OGPGM(1:5), and OGPGM(1:10) under the loading of 2 N (n = 3). (D, E) The storage modulus of Gelatin, OG, OGPGM(1:5), and OGPGM(1:10) (n = 3). (F) The loss modulus of Gelatin, OG, OGPGM(1:5), and OGPGM(1:10). (Data presented as mean ± SD, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant).
Fig. 3
Fig. 3
Biocompatibility and residency of OGPGM. (A) Schematic representation of OG and OGPGM co-cultured with chondrocytes (n = 3). (B) Live-dead staining of OG and OGPGM after 1, 3, and 5 days of co-culture with chondrocytes (n = 3). (C) Quantitative evaluation of live cells. (D) CCK8 detection of chondrocyte proliferation under co-culture with OG and OGPGM (n = 3). (E) HE staining images of various organs at 0, 4, and 8 weeks after local injection of OG and OGPGM (n = 3). (F). Release curve of PGA-Mn from OGPGM (n = 3). (G, H) In vivo imaging of cy5.5-labeled PGA-Mn in rat joints after local injection of PGA-Mn and OGPGM (n = 3). (Data presented as mean ± SD, *P < 0.05, ***P < 0.001, ****P < 0.0001, ns, not significant).
Fig. 4
Fig. 4
ROS scavenging activity of PGA-Mn and OGPGM. (A–D) Clearance of ABTS, ·OH, H2O2, and ·O2− by PGA-Mn with increasing concentration (n = 3). (E–F) UV characteristic absorption of PGA-Mn ABTS, ·OH, H2O2, ·O2− over time (n = 3). (I–K) Fluorescence micrographs (1), flow cytometry (2), and intensity quantification (3) show the activities of OGPGM to scavenge different types of ROS in chondrocytes with H2O2 treatment (n = 3). (H) Live/dead Fluorescence micrographs of chondrocytes under different treatments (n = 3). (Data presented as mean ± SD, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant).
Fig. 5
Fig. 5
OGPGM alleviated chondrocyte inflammation and promoted ECM synthesis (A, B) Representative immunofluorescence staining images display the protein expression level of COL2, MMP13, TNF-α, and IL-1β in the H2O2 treated chondrocytes, which are co-cultured with the OG and OGPGM for 12 h. Green: COL2; Blue: cell nuclei; Red: cell F-actin. (n = 3) (C–F) Relative fluorescence quantitative analysis of TNF-α, IL-1β, MMP13, and COL2 in different groups. (G) Western blot analysis and semi quantification of TNF-α, IL-1β, MMP13, and COL2 proteins (n = 3). (I–K) Relative protein expression of TNF-α, IL-1β, MMP13 and COL2. (Data presented as mean ± SD, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant).
Fig. 6
Fig. 6
The radiological data of animal experiments. (A) Overview of animal experiments. (B) Representative x-ray (n = 5) and (C) micro-CT images in anterior-posterior (AP) and lateral (LAT) view of the knee joint (n = 5). (D) Relative knee joint gap widths on the LAT and (E) AP of the knee in different groups of X-rays (F) The relative osteophyte volume measured from micro-CT images. (Data presented as mean ± SD, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant).
Fig. 7
Fig. 7
The histological data of animal experiments. (A) Macroscopic observation of the femur. (B) Representative images of HE staining and (C) Safranin O-fast green staining from each group at 8 weeks after surgery (n = 5). (D) IHC of COL2 and MMP13 at 8 weeks after surgery (n = 5). (E) OARSI score, (F) and Mankin score of knee joint tissue. (G) Apoptosis level of chondrocytes in the knee joint detected by TUNEL (n = 5). (H) TNF-α characterized by knee joint tissue immunofluorescent staining (n = 5). (I) Quantification of the relative expression of collagen II and (J)MMP -13 (n = 5). (K) Percentage of TUNEL-positive cell nuclei. (L) Relative fluorescence intensity of TNF-α. The white dotted lines point toward the surface of the articular cartilage. (Data presented as mean ± SD, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant).
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