, Hockin H. Xu, Michael D. Weir, WahWah Thein-Han
Human umbilical cord mesenchymal stem cells (hUCMSCs) are a promising alternative to bone marrow MSCs, which require invasive procedures to harvest. The objectives of this study were to develop a novel non-rigid and tough calcium phosphate cement (CPC), and to investigate hUCMSC proliferation, osteodifferentiation and mineralization on non-rigid CPC for the first time. Non-rigid CPC scaffold was fabricated using extra tetracalcium phosphate in the CPC powder, chitosan, absorbable fibers and alginate microbeads. The non-rigid CPC-microbead scaffold possessed a strain-at-failure of 10.7%, higher than conventional CPCs strain of 0.05%, which is typical for brittle bioceramics. The flexural strength of non-rigid CPC-microbead scaffold was 4-fold that of rigid CPC-mircobead scaffold. Work-of-fracture (toughness) was increased by 20-fold. The non-rigid CPC-microbead-fiber scaffold matched the strength of cancellous bone. hUCMSCs on non-rigid CPC increased from about 100 cells/mm2 at 1 d, to 600 cells/mm2 at 8 d. Alkaline phosphatase, osteocalcin, and collagen gene expressions of hUCMSCs were greatly increased, and the cells successfully synthesized bone minerals. hUCMSCs on non-rigid CPC-microbead-fiber construct had higher bone marker expressions and more mineralization than those on rigid CPC. Non-rigid CPC could potentially provide compliance for micro-motions within the tissues, with load-supporting strength for periodontal bone repair, spinal fusion and other repairs. In conclusion, this study developed the first non-rigid, self-setting calcium phosphate-microbead scaffold with a strain-at-failure exceeding 10%. hUCMSCs showed excellent proliferation, osteodifferentiation, and mineral synthesis on non-rigid CPC scaffolds. The hUCMSC-CPC construct with excellent cell proliferation, osteodifferentiation and mineral synthesis is promising for bone regeneration.
Calcium phosphate cement, non-rigid scaffold, human umbilical cord stem cells, osteogenic differentiation, bone tissue engineering