Comparison of bone graft matrices for human mesenchymal stem cell-directed osteogenesis

Scaffolds to support cell-based tissue engineering are critical determinants of clinical efforts to regenerate and repair the body. Bone tissue engineering requires materials that are biocompatible, well vascularized, mechanically suited for bone function, integrated with the host skeleton, and support osteoinduction of the implanted cells that form new bone. The aim of this study was to compare the osteogenic potential of bone marrow-derived, culture expanded human mesenchymal stem cells (hMSCs) adherent to different scaffolds composed of various calcium phosphates. Cells were loaded onto 2 x 2 mm cubes of coral calcium carbonate-derived apatite, bovine bone-derived apatite, synthetic hydroxyapatite (HA)/tricalcium phosphate (TCP) (60:40%), or synthetic HA/TCP (20:80%) and placed into the dorsum of SCID mice for 5 weeks. Subsequent histomorphometric analysis of bone formation within the cubes revealed the absence of bone formation within the coral-derived apatite and the bovine bone-derived apatite. Bone formation within synthetic HA/TCP scaffolds was measured to be 8.8% (+/-2.7%) and 13.8% (+/-3.6%) of the total tissue present for the 60:40% and 20:80% materials, respectively. Minimal resorption was observed at this early time point. Scanning electron microscopy evaluation of loaded scaffolds indicates that cell loading was not a variable affecting the different bone formation outcomes in these four scaffolds. In this ectopic model, different apatite-containing scaffolds of similar morphology and porosity demonstrated marked differences in their ability to support osteoinduction by implanted hMSCs. The necessary induction of hMSCs along the osteoblastic lineage may be dependent, in part, on the local microenvironment established by the scaffold chemistry and interactions with the host.