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Sustained spatiotemporal release of TGF‐β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns
Author(s) -
Asen AnnKathrin,
Goebel Lars,
ReyRico Ana,
Sohier Jerome,
Zurakowski David,
Cucchiarini Magali,
Madry Henning
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800105r
Subject(s) - chondrogenesis , transforming growth factor , microbiology and biotechnology , biology , stem cell
The continuous presence of TGF‐β is critically important to induce effective chondrogenesis. To investigate chondrogenesis in a cartilage defect, we tested the hypothesis that the implantation of TGF‐β1‐releasing scaffolds improves very early cartilage repair in vivo. Spatiotemporal controlled release of TGF‐β1 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‐β1 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‐β1 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‐β1 modulates early chon‐ drogenesis 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‐ β1 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‐β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns. FASEB J. 32, 5298–5311 (2018). www.fasebj.org