Research ArticleTissue Engineering

Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep

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Science Translational Medicine  10 Dec 2014:
Vol. 6, Issue 266, pp. 266ra171
DOI: 10.1126/scitranslmed.3009696

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Bioprinting Cartilage Scaffolds

Weak in the knees? You may need more cartilage. Because donor cartilage as well as synthetic products are scarce, Lee et al. devised a way to regenerate the knee meniscus, using the native tissue from sheep knees as inspiration. The authors three-dimensionally (3D) printed poly-ε-caprolactone (PCL) scaffolds based on the anatomically correct dimensions of the native meniscus. These scaffolds were loaded at specific locations with polymeric microspheres containing one of two growth factors, to be released sequentially. Connective tissue growth factor (CTGF) was released first, followed by transforming growth factor–β3 (TGFβ3). Control over both spatial and temporal protein release allowed for zone-specific matrix development: type I collagen in the outer zone and type II collagen in the inner zone, similar to the native meniscus. It is believed that such growth factor release induced endogenous stem cells to differentiate into fibrochondrocytes—the cells that make up the meniscus. In vivo in a large animal (sheep) model, the implanted scaffolds led to tissue regeneration with desired mechanical properties. If translated to humans, this acellular biomaterial would fulfill the major unmet need of repairing deteriorated cartilage in not only the knees but also tendon-bone junctions, the intervertebral discs of the spine, and the temporomandibular joint.

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