Irradiated bone has a greater risk of implant failure than nonirradiated bone. The purpose of this study was to investigate the influence of cell sheets composed of co-cultured bone marrow mesenchymal stromal cells (BMSCs) and endothelial progenitor cells (EPCs) on implant osseointegration in irradiated bone. Cell sheets (EPCs, BMSCs or co-cultured EPCs and BMSCs) were wrapped around titanium implants to make cell sheet-implant complexes. The co-cultured group showed the highest osteogenic differentiation potential in vitro, as indicated by the extracellular matrix mineralization and the expression of osteogenesis related genes at both mRNA and protein levels. The co-cultured cells promoted ectopic bone formation as indicated by micro-computed tomography (Micro-CT) and histological analysis. In the irradiated tibias of rats, implants of the co-cultured group showed enhanced osseointegration by Micro-CT evaluation and histological observation. Co-cultured EPCs and BMSCs also up-regulated the expression of osteogenesis related genes in bone fragments in close contact with implants. In conclusion, cell sheets of co-cultured EPCs and BMSCs could promote osseous healing around implants and are potentially useful to improve osseointegration process for patients after radiotherapy.

The dysregulation of immune system plays a crucial function in periodontitis development. Pro-inflammatory cytokines are thought to be critical for the generation and development of periodontitis. The enhanced activity of osteoclasts contributes to periodontitis pathogenesis. Nuclear factor-κB (NF-κB) signaling pathway directly enhances osteoclast differentiation and maturation. 2-[(aminocarbonyl)amino]-5-(4fluorophenyl)-3-thiophenecarboxamide (TPCA-1) is a IκB kinases (IKK) inhibitor. This research aimed to investigate whether TPCA-1 had influence on the pathogenesis of chronic periodontitis. Mouse chronic periodontitis was induced by an in vivo ligatureinduced periodontitis model. TPCA-1 was intravenously injected into mice after chronic periodontitis induction. Bone marrow-derived macrophages were cultured in macrophage colony-stimulating factor (M-CSF)-conditioned media with receptor activator of nuclear factor-kappa B ligand (RANKL) induce in vitro osteoclast differentiation. Western blot was used to analyze protein levels and mRNA levels were analyzed through qRT-PCR. TPCA-1 promoted osteoclastogenesis and osteoclastrelated gene expression in vitro. The production of pro-inflammatory cytokines in osteoclasts induced by lipopolysaccharides was inhibited by TPCA-1 in vitro. In vitro TPCA-1 treatment inhibited Aggregatibacter actinomycetemcomitans (A.a)-induced expression of pro-inflammatory cytokines and NF-κB signal activation in osteoclasts. The induction of chronic periodontitis was inhibited by the absence of IKKb in mice.This research demonstrates that the treatment of TPCA-1 negatively regulates inflammation response and inhibits the osteoclastogenesis through the inactivation of NF-κB pathway in mouse chronic periodontitis model.

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