Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov 30;13(50):34958-34971.
doi: 10.1039/d3ra06222h.

In situ fabrication of an anisotropic double-layer hydrogel as a bio-scaffold for repairing articular cartilage and subchondral bone injuries

Affiliations

In situ fabrication of an anisotropic double-layer hydrogel as a bio-scaffold for repairing articular cartilage and subchondral bone injuries

Xiaotian Yu et al. RSC Adv. .

Abstract

Articular cartilage is a smooth and elastic connective tissue playing load-bearing and lubricating roles in the human body. Normal articular cartilage comprises no blood vessels, lymphatic vessels, nerves, or undifferentiated cells, so damage self-repair is very unlikely. The injuries of articular cartilage are often accompanied by damage to the subchondral bone. The subchondral bone mainly provides mechanical support for the joint, and the successful repair of articular cartilage depends on the ability of the subchondral bone to provide a suitable environment. Currently, conventional repair treatments for articular cartilage and subchondral bone defects can hardly achieve good results due to the poor self-repairing ability of the cartilage Here, we propose a bioactive injectable double-layer hydrogel to repair articular cartilage and subchondral bone. The hydrogel scaffold mimics the multilayer structure of articular cartilage and subchondral bone. Agarose was used as a common base material for the double-layer hydrogel scaffold, in which a sodium alginate (SA)/agarose layer was used for the repair of artificially produced subchondral bone defects, while a decellularized extracellular matrix (dECM)/agarose layer was used for the repair of articular cartilage defects. The double-layer hydrogel scaffold is injectable, easy to use, and can fill in the damaged area. The hydrogel scaffold is also anisotropic both chemically and structurally. Animal experiments showed that the surface of the new cartilage tissue in the double-layer hydrogel scaffold group was closest to normal articular cartilage, with a structure similar to that of hyaline cartilage and a preliminary calcified layer. Moreover, the new subchondral bone in this group exhibited many regular bone trabeculae, and the new cartilage and subchondral bone were mechanically bound without mutual intrusion and tightly integrated with the surrounding tissue. The continuous double-layer hydrogel scaffold prepared in this study mimics the multilayer structure of articular cartilage and subchondral bone and promotes the functional repair of articular cartilage and subchondral bone, favoring close integration between the newborn tissue and the original tissue.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Fig. 1
Fig. 1. Changes in the content of various components before and after decellularization of cartilage tissue: (a) collagen; (b) GAG; (c) dsDNA; (d) α-Gal. The HE staining images of (e) normal cartilage tissue; (f) dECM.
Fig. 2
Fig. 2. SEM images of (a) SA/agarose hydrogel; (b) DECM/agarose hydrogel. cryogenic SEM images of (c) double-layer hydrogel (longitudinal cutting); (d) double-layer hydrogel (cross-sectional cutting).
Fig. 3
Fig. 3. (a) Storage modulus and (b) swelling ratio of three as-synthesized hydrogels. (c) The biodegradation efficiency of SA/agarose/dECM hydrogel.
Fig. 4
Fig. 4. The proliferation level of cells cultured in (a) SA/agarose hydrogel, (b) dECM/agarose hydrogel, and (c) double-layer hydrogel.
Fig. 5
Fig. 5. Gene expression levels of cells in different hydrogels: (a) ALP; (b) collagen I; (c) Acan; (d) collagen II.
Fig. 6
Fig. 6. The appearance of articular cartilage injury samples with different hydrogels at week 4 and week 8.
Fig. 7
Fig. 7. HE staining images of the samples at different conditions.
Fig. 8
Fig. 8. Safranine O-fast green staining images of the samples at different conditions.
Fig. 9
Fig. 9. Type II collagen IHC staining images of the samples at different conditions.

Similar articles

Cited by

References

    1. Cole B. J. Redondo M. L. Cotter E. J. Cartilage. 2021;12:139–145. - PMC - PubMed
    1. Huang B. J. Hu J. C. Athanasiou K. A. Biomaterials. 2016;98:1–22. - PMC - PubMed
    1. Zhang Q. Hu Y. Long X. Hu L. Wu Y. Wu J. Shi X. Xie R. Bi Y. Yu F. Li P. Yang Y. Front. Bioeng. Biotechnol. 2022;10:908082. - PMC - PubMed
    1. Goldberg A. Mitchell K. Soans J. Kim L. Zaidi R. J. Orthop. Surg. Res. 2017;12:39. - PMC - PubMed
    1. Murphy M. P. Koepke L. S. Lopez M. T. Tong X. Ambrosi T. H. Gulati G. S. Marecic O. Wang Y. Ransom R. C. Hoover M. Y. Steininger H. Zhao L. Walkiewicz M. P. Quarto N. Levi B. Wan D. C. Weissman I. L. Goodman S. B. Yang F. Longaker M. T. Chan C. K. F. Nat. Med. 2020;26:1583–1592. - PMC - PubMed