Porous Scaffolds Derived from Devitalized Tissue Engineered Cartilaginous Matrix Support Chondrogenesis of Adult Stem Cells

ECM-derived scaffolds have previously been developed from devitalized native cartilage and successfully used in tissue engineering. Such ECM-based biomaterials are commonly derived from animal tissue, which may not represent the ideal source for applications in human. Native human ECM can be used as an alternative to xenogeneic tissue; however, its supply may be limited, leading to the need for a more readily available source of such biomaterials. The objective of this study was to compare devitalized native and tissue engineered cartilaginous ECM as chondro-permissive scaffolds for tissue engineering. To this end, porous scaffolds were produced using ECM derived from porcine articular cartilage and cartilaginous sheets engineered using human bone marrow stem cells. An identical process was used to produce scaffolds from three different types of devitalized ECMs, namely that derived from porcine cartilage (Native), human engineered cartilaginous sheets (Eng), and human engineered cartilaginous sheets generated in the presence of growth factor releasing microspheres (Eng-MS). Scaffolds produced using both devitalized engineered and native ECM possessed similar mechanical properties, pore size and GAG content, although were compositionally distinct. After being seeded with human infrapatellar fat pad stem cells, the engineered ECM-derived scaffolds (no Microspheres) supported less robust cartilage matrix deposition than native ECM scaffolds. However, more chondro-permissive scaffolds could be generated using cartilaginous ECM engineered in the presence of TGF-β1 releasing microspheres. Eng-MS scaffolds supported comparable levels of GAG synthesis to native ECM scaffolds. These results demonstrate that engineered ECM can be used to produce scaffolds for cartilage tissue engineering, overcoming stock limitations and other barriers associated with native autogeneic, allogeneic, and xenogeneic tissues. Such engineered ECM holds significant promise as an off-the-shelf chondro-permissive scaffold for articular cartilage repair.