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

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.

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.

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

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

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

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

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

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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