Sustained spatiotemporal release of TGF-ß1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns.

ABSTRACT

The continuous presence of TGF-ß is critically important to induce effective chondrogenesis. To investigate chondrogenesis in a cartilage defect, we tested the hypothesis that the implantation of TGF-ß1-releasing scaffolds improves very early cartilage repair in vivo. Spatiotemporal controlled release of TGF-ß1 was achieved from multiblock scaffolds that were implanted in osteochondral defects in the medial femoral condyles of adult minipigs. We observed a sustained presence of TGF-ß1 at 4 wk in vivo, which significantly promoted structural aspects of early overall cartilage repair, especially cellularity, cellular morphology, and safranin O staining intensity. Furthermore, early aggrecan and type II collagen production were both increased in specific topographic patterns in cartilaginous repair tissue. Sustained release of TGF-ß1 also increased cell numbers and proliferation, staining intensities for the stem cell surface marker, CD105, and number of stromal cell-derived factor-1 (SDF-1) -positive cells within cartilaginous repair tissue. These data identify a mechanism by which TGF-ß1 modulates early chondrogenesis by primarily increasing the number of progenitor cells arising from the subchondral bone marrow compartment via the SDF-1/chemokine (CXC motif) receptor 4 pathway, their proliferation, differentiation, and extracellular matrix deposition in specific topographic patterns, highlighting the pivotal role played by TGF-ß1 during this crucial phase.-Asen, A.-K., Goebel, L., Rey-Rico, A., Sohier, J., Zurakowski, D., Cucchiarini, M., Madry, H. Sustained spatiotemporal release of TGF-ß1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns.