The effective healing of a bone defect is dependent on the careful coordination of inflammatory and bone-forming cells. In the current work, pro-inflammatory M1 and anti-inflammatory M2 macrophages were co-cultured with primary murine bone mesenchymal stem cells (BMSCs), in vitro, to establish the cross-talk among polarized macrophages and BMSCs, and as well as their effects on osteogenesis. Meanwhile, macrophages influence the osteogenesis of BMSCs through paracrine forms such as exosomes. We focused on whether exosomes of macrophages promote osteogenic differentiation. The results indicated that M1 and M2 polarized macrophage exosomes all can promote osteogenesis of BMSCs. Especially, M1 macrophage-derived exosomes promote osteogenesis of BMSCs through microRNA-21a-5p at the early stage of inflammation. This research helps to develop an understanding of the intricate interactions among BMSCs and macrophages, which can help to improve the process of bone healing as well as additional regenerative processes by local sustained release of exosomes.

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In order to establish and standardize the rabbit rib segmental bone defect model, it is of vital importance to determine rabbit rib critical size defect (CSD). According to the general time needed for spontaneous long-bone regeneration, three-month observation period was set to determine the CSD. The rabbit rib segmental bone defects with different sizes from 1 to 5 cm with or without periosteum were performed in the eighth rib of 4-month-old male New Zealand rabbits and underwent X-ray examinations at the 4th, 8th and 12th weeks postoperatively. The gross and histological examinations at postoperative week 12 were evaluated, which showed that the critical sizes in the rabbit rib models with and without periosteum were 5 and 2 cm, respectively. This study provides prerequisite data for establishing rabbit rib CSD model and evaluating bone materials using this model.