Pro-Regenerative Fibroblasts Induced by Bioactive Ceramics Promote Bone Formation

Objectives: Heterogeneity of fibroblast have been reported to influence the tissue regeneration, however, whether the phenotype of fibroblast induced by bioactive ceramics regulate bone formation is unclear.
Methods: Ectopic bone formation model with biphasic calcium phosphate ceramics (BCP) was used to investigate the temporal and spatial distribution of fibroblasts and fibrosis. The effect of BCP on fibroblast cell line L929 was evaluated by EdU kit, transwell assay and rt-PCR. Further, the effect of its conditioned media on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was confirmed by ALP and ARS staining.
Results: SEM and X-RD showed that BCP contained micro- and macro-pores and consisted of hydrogen-apatite and β-tricalcium phosphate. And then, BCP implanted into mice muscle successfully induced osteoblast-like cell and bone-like formation. Fibroblast labelled by vimentin marker gathered around materials after 7d post implantation but fibrosis was not clear. In vitro, BCP inhibited growth of L929 fibroblast but promoted its migration. Moreover, Col-1a1 and Pcna genes were increased significantly but Tgf-β in L929 did not changed. ALP and ARS staining showed the conditioned media from L929 stimulated by BCP could enhance osteogenic differentiation of BMSCs.
Conclusions: In conclusion, phenotype of fibroblast colud be regulated by bioactive ceramics to enhance bone formation.