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Biomimetic cartilage-lubricating polymers regenerate cartilage in rats with early osteoarthritis

Abstract

The early stages of progressive degeneration of cartilage in articular joints are a hallmark of osteoarthritis. Healthy cartilage is lubricated by brush-like cartilage-binding nanofibres with a hyaluronan backbone and two key side chains (lubricin and lipid). Here, we show that hyaluronan backbones grafted with lubricin-like sulfonate-rich polymers or with lipid-like phosphocholine-rich polymers together enhance cartilage regeneration in a rat model of early osteoarthritis. These biomimetic brush-like nanofibres show a high affinity for cartilage proteins, form a lubrication layer on the cartilage surface and efficiently lubricate damaged human cartilage, lowering its friction coefficient to the low levels typical of native cartilage. Intra-articular injection of the two types of nanofibre into rats with surgically induced osteoarthritic joints led to cartilage regeneration and to the abrogation of osteoarthritis within 8 weeks. Biocompatible injectable lubricants that facilitate cartilage regeneration may offer a translational strategy for the treatment of early osteoarthritis.

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Fig. 1: Illustration of the overall idea.
Fig. 2: Chemical structures of HA/PA and HA/PM.
Fig. 3: Evaluation of the binding modes between HA/PA and HA/PM.
Fig. 4: Evaluation of the retention of Cy5-labelled biomimetic lubricants (HA/PA and HA/PM) in the OA rat joint environment.
Fig. 5: Confirmation of the recognition between the biomimetic lubricants (HA/PA and HA/PM) and the cartilage proteins in the presence of proteins in synovial fluid and the lubrication of human cartilage using the biomimetic lubricants.
Fig. 6: Tissue compatibility of HA/PA and HA/PM determined using an in vitro 3D cartilage model (LhCG) and healthy rats.
Fig. 7: Evaluation of the chondroprotective effect and ability of HA/PA and HA/PM (alone or in combination) to treat OA in rats.
Fig. 8: Evaluation of the ability of HA/PA and HA/PM (alone or in combination) in promoting cartilage regeneration to treat OA in rats.

Data availability

The main data supporting the results of this study are available within the paper and its supplementary information. The raw and analysed datasets generated during the study are too large to be publicly shared; however, they are available for research purposes from the corresponding authors upon reasonable request.

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Acknowledgements

We sincerely thank X. Miao from South China University of Technology for her contributions to the AFM characterizations. We also sincerely appreciate the help and guidance of F. Zhang and S. Jiang from Sun Yat-Sen University for the anterior-cruciate-ligament-transection-induced OA surgery. S.L. and L.R. are thankful for financial support from the National Natural Science Foundation of China (51673071), the Natural Science Foundation of Guangdong Province (2016A030313509), the Guangdong Scientific and Technological Project (2014B090907004), and the National Key Research and Development Program of China (2017YFC1105004). Y.Z. and C.M. would like to acknowledge support from the Institute for Biomedical Engineering, Science and Technology of the University of Oklahoma.

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R.X., S.L., L.R. and C.M. supervised the project. H.Y. carried out the synovial stem cell experiments under the supervision of D.-A.W. R.X., H.Y., A.S.M., Y.Z., Y.J., M.G., Y.C. and L.W. carried out the rest of the experiments and characterization. D.Q. assisted in analysing the confocal results, and K.W. provided fruitful discussion in the results of the animal experiments. A.S.M. designed the illustrations and edited the writing. All the authors contributed to the discussions and writing of the manuscript.

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Correspondence to Sa Liu, Li Ren or Chuanbin Mao.

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Xie, R., Yao, H., Mao, A.S. et al. Biomimetic cartilage-lubricating polymers regenerate cartilage in rats with early osteoarthritis. Nat Biomed Eng 5, 1189–1201 (2021). https://doi.org/10.1038/s41551-021-00785-y

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