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Multifunctional chondroitin sulphate for cartilage tissue–biomaterial integration

Abstract

A biologically active, high-strength tissue adhesive is needed for numerous medical applications in tissue engineering and regenerative medicine. Integration of biomaterials or implants with surrounding native tissue is crucial for both immediate functionality and long-term performance of the tissue. Here, we use the biopolymer chondroitin sulphate (CS), one of the major components of cartilage extracellular matrix, to develop a novel bioadhesive that is readily applied and acts quickly. CS was chemically functionalized with methacrylate and aldehyde groups on the polysaccharide backbone to chemically bridge biomaterials and tissue proteins via a twofold covalent link. Three-dimensional hydrogels (with and without cells) bonded to articular cartilage defects. In in vitro and in vivo functional studies this approach led to mechanical stability of the hydrogel and tissue repair in cartilage defects.

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Figure 1: Synthesis and characterization of CS adhesive.
Figure 2: Schematic diagram of CS-adhesive application and hydrogel integration.
Figure 3: Integration of hydrogels and developing tissue to the cartilage surface with CS adhesive.
Figure 4: CS-adhesive mechanical properties and in vivo durability.
Figure 5: CS adhesive and cartilage repair in a large-animal model.

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Acknowledgements

We acknowledge S. Ramaswamy and R. Spencer for MRI access; J. Cooper and S.-h. Moon for use of mechanical analysis facilities; and N. Marcus for assistance in the animal studies and critical review of the manuscript. The authors would like to acknowledge the Materials Science Department at Johns Hopkins University for use of the surface analysis laboratory. This research was financially supported by NIH Grant No. R21 EB002369-01, R01 EB05517-01, the State of Maryland University Technology Development Fund and Cartilix.

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D.W. was responsible for synthesis. S.V., I.S., J.G. and D.F. were responsible for chemical analysis. B.S., S.F. and B.C. were responsible for rabbit and goat studies. J.H.E. was responsible for design, data analysis and manuscript preparation.

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Correspondence to Jennifer H. Elisseeff.

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Competing interests

J.E. is a founder of and consultant to Cartilix.

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Supplementary figure 1 and supplementary methods (PDF 156 kb)

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Wang, DA., Varghese, S., Sharma, B. et al. Multifunctional chondroitin sulphate for cartilage tissue–biomaterial integration. Nature Mater 6, 385–392 (2007). https://doi.org/10.1038/nmat1890

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