Background/Aims: Human bone-marrow mesenchymal stem cells (hBMSCs) are widely transplanted into inflammatory microenvironment to accelerate tissue regeneration. Transplanted hBMSCs recruit host hBMSCs through a poorly understood mechanism. This study was aimed to determine whether and how inflammatory microenvironment influenced the host-hBMSCs-recruiting capability of transplanted hBMSCs. Methods: Pro-inflammatory factors, including IL-1β, IL-6 and TNF-α, were utilized to mimic inflammatory microenvironment. hBMSCs were cultured and conditioned media (CM) were collected. The effects of inflammatory microenvironment on the host-hBMSCs-recruiting capability of cultured hBMSCs were revealed by transwell migration assays. Employing semi-quantitative and quantitative cytokine antibody assays, we examined the secretory profile of cultured hBMSCs. Results: CM from cultured hBMSCs exerted excellent host-hBMSCs-recruiting capability, which was significantly promoted by exposure to inflammatory microenvironment. Within inflammatory microenvironment, hBMSCs secreted more chemokines related to cell migration. Finally, 21 cytokines were verified as potential factors accounting for the enhanced host-hBMSCs-recruiting capability of cultured hBMSCs exposed to inflammatory microenvironment. Conclusion: These results strongly suggested that in clinic, inflammatory microenvironment might promote the host-hBMSCs-recruiting capacity of transplanted hBMSCs by increasing chemokines secretion. Modulation of such characteristics of hBMSCs might provide novel therapeutic ideas in the context of hBMSCs.

Bone defect complicated by infection remains a major challenge in orthopedic surguries, and bone grafting for primary repair often associates with high failure rate. The rapid progress in the research spectrums of tissue-engineered bone and antibiotic delivery systems bring hope to solve this issue. Herein, we evaluated the local anti-infective and osteogenic potential of an injectable anti-infection tissue-engineered construct, which includes a fibrin gel scaffold and vancomycin alginate beads (Vanco-AB) to form composites, in the treatment of chronic osteomyelitis with bone defect in rabbit tibia. The infected bone defect model of rabbit tibia was established. Then, the bone defects in the proximal tibial metaphysis were implanted with the constructed composites, containing different combinations of mesenchymal stem cells and Vanco-AB. The in vivo capacities of anti-infection and local osteogenesis of the grafts were determined using radiographic assessment, histopathological observation, and microorganism cultures. Results showed that the injectable anti-infection tissue-engineered construct, comprising a fibrin gel scaffold and Vanco-AB led to efficient eradication of bacteria. At 1 and 3 months after transplantation, the radiographic assessment and microbiological examination demonstrated that the sustained antibiotic release by Vanco-AB significantly decreased the Norden scores of osteomyelitis, generated negative results for the presence of bacteria, and reduced the relapse of osteomyelitis. Meanwhile, tissue-engineered construct implanted in one-stage promoted local bone repair and reconstruction, and it exhibited more apparent osteogenic potential, compared to the control group (without Vanco-AB). In conclusion, the current study achieved the primary repair of bone defect with infection, thus providing an alternative treatment strategy for infected bone defect, which occurs commonly in chronic osteomyelitis.

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