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Nanofibrous hollow microspheres self-assembled from star-shaped polymers as injectable cell carriers for knee repair

Nature Materials volume 10, pages 398–406 (2011)Cite this article

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Abstract

To repair complexly shaped tissue defects, an injectable cell carrier is desirable to achieve an accurate fit and to minimize surgical intervention. However, the injectable carriers available at present have limitations, and are not used clinically for cartilage regeneration. Here, we report nanofibrous hollow microspheres self-assembled from star-shaped biodegradable polymers as an injectable cell carrier. The nanofibrous hollow microspheres, integrating the extracellular-matrix-mimicking architecture with a highly porous injectable form, were shown to efficiently accommodate cells and enhance cartilage regeneration, compared with control microspheres. The nanofibrous hollow microspheres also supported a significantly larger amount of, and higher-quality, cartilage regeneration than the chondrocytes-alone group in an ectopic implantation model. In a critical-size rabbit osteochondral defect-repair model, the nanofibrous hollow microspheres/chondrocytes group achieved substantially better cartilage repair than the chondrocytes-alone group that simulates the clinically available autologous chondrocyte implantation procedure. These results indicate that the nanofibrous hollow microspheres are an excellent injectable cell carrier for cartilage regeneration.

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Figure 1: A schematic of SS-PLLA synthesis and nanofibrous hollow microsphere fabrication.
Figure 2: Characterization of nanofibrous hollow microspheres, nanofibrous microspheres and solid-interior microspheres.
Figure 3: Assessment of chondrocyte adhesion and in vitro cartilage tissue formation on different microspheres.
Figure 4: Comparison of various microspheres as cell carriers for ectopic cartilage regeneration in vivo.
Figure 5: Comparison between neo-cartilage tissues regenerated from nanofibrous hollow microspheres/chondrocytes and PEG/chondrocytes constructs after eight weeks of subcutaneous implantation in nude mice.
Figure 6: Evaluation of critical-size rabbit osteochondral defect repair eight weeks after injection.

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Acknowledgements

The authors would like to acknowledge the financial support from the National Institutes of Health (Research Grants DE015384 and DE017689: P.X.M.). The authors would also like to acknowledge the assistance from J. Hu in the animal experiments.

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Author notes

  1. Xiaohua Liu and Xiaobing Jin: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Biologic and Materials Sciences, 1011 North University Ave., Room 2211, University of Michigan, Ann Arbor, Michigan 48109-1078, USA

    Xiaohua Liu, Xiaobing Jin & Peter X. Ma

  2. Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109-1078, USA

    Peter X. Ma

  3. Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, Michigan 48109-1078, USA

    Peter X. Ma

  4. Department of Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109-1078, USA

    Peter X. Ma

Authors
  1. Xiaohua Liu
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  3. Peter X. Ma
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Contributions

X.L. and X.J. contributed overall equally to the experimental work. X.L. carried out the polymer synthesis, fabrication of microspheres and structural characterization. X.J. carried out the cell culture, animal studies and tissue analyses. P.X.M. was responsible for the overall project design and manuscript organization. All authors contributed to the scientific planning, data analysis and interpretation.

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Correspondence to Peter X. Ma.

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The authors declare no competing financial interests.

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Liu, X., Jin, X. & Ma, P. Nanofibrous hollow microspheres self-assembled from star-shaped polymers as injectable cell carriers for knee repair. Nature Mater 10, 398–406 (2011). https://doi.org/10.1038/nmat2999

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