Research ArticleTissue Engineering

Long-term mechanical function and integration of an implanted tissue-engineered intervertebral disc

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Science Translational Medicine  21 Nov 2018:
Vol. 10, Issue 468, eaau0670
DOI: 10.1126/scitranslmed.aau0670

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Dependable discs

Intervertebral disc degeneration causes back and neck pain, sometimes necessitating disc fusion surgery. Although fusion may alleviate symptoms, it does not address the underlying cause of degeneration. As an alternative to fusion, Gullbrand and colleagues developed tissue-engineered discs for disc replacement by sandwiching hydrogel and polymer materials seeded with cartilage or mesenchymal stem cells between acellular polymer endplates. Engineered discs integrated with native discs, maintaining their structure and showing near-native mechanical properties 5 months after implantation in a rodent disc replacement model. Similar results were seen 2 months after implantation in a goat model, demonstrating the translational feasibility of this tissue engineering approach.

Abstract

Tissue engineering holds great promise for the treatment of advanced intervertebral disc degeneration. However, assessment of in vivo integration and mechanical function of tissue-engineered disc replacements over the long term, in large animal models, will be necessary to advance clinical translation. To that end, we developed tissue-engineered, endplate-modified disc-like angle ply structures (eDAPS) sized for the rat caudal and goat cervical spines that recapitulate the hierarchical structure of the native disc. Here, we demonstrate functional maturation and integration of these eDAPS in a rat caudal disc replacement model, with compressive mechanical properties reaching native values after 20 weeks in vivo and evidence of functional integration under physiological loads. To further this therapy toward clinical translation, we implanted eDAPS sized for the human cervical disc space in a goat cervical disc replacement model. Our results demonstrate maintenance of eDAPS composition and structure up to 8 weeks in vivo in the goat cervical disc space and maturation of compressive mechanical properties to match native levels. These results demonstrate the translational feasibility of disc replacement with a tissue-engineered construct for the treatment of advanced disc degeneration.

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