Additive manufacturing of cartilage-mimetic scaffolds as off-the-shelf implants for joint regeneration.

Biomimetic scaffolds that provide a tissue-specific environment to cells are particularly promising for tissue engineering and regenerative medicine applications. The goal of this study was to integrate emerging additive manufacturing and biomaterial design strategies to produce articular cartilage (AC) mimetic scaffolds that could be used as 'off-the-shelf' implants for joint regeneration. To this end alginate sulfate, a sulfated glycosaminoglycan (sGAG) mimic, was used to functionalize porous alginate-based scaffolds and to support the sustained release of transforming growth factor-β3 (TGF-β3). Covalent crosslinking dramatically improved the elasticity of the alginate/alginate sulfate scaffolds, while scaffold architecture could be tailored using a directional freezing technique. Introducing such an anisotropic architecture was found to promote mesenchymal stem cell (MSC) infiltration into the scaffold and to direct the orientation of the deposited extracellular matrix, leading to the development of cartilage tissue with a biomimetic zonal architecture. In vitro experiments also demonstrated the capacity of the sulfated scaffolds to both enhance chondrogenesis of MSCs and to control the release of TGF-β3, leading to the development of a tissue rich in sGAG and type II collagen. The scaffolds were further reinforced with a 3D printed PLCL framework, leading to composite implants that were more elastic than those reinforced with PCL, and which better mimicked the bulk mechanical properties of native cartilage tissue. The ability of this composite scaffold to support chondrogenesis was then confirmed within a dynamic culture system. Altogether, these findings demonstrate the potential of such biomimetic scaffolds as putative 'single-stage' or 'off-the-shelf' strategies for articular cartilage regeneration.