Background In diabetes, delayed wound healing was considered as the result of excessive recruitment and retention of pro-inflammatory cells and factors. Hematopoietic prostaglandin D synthase (HPGDS) was identified from differently expressed genes of diabetic human foot skin. HPGDS is responsible for the production of prostaglandin D2 (PGD2), an inflammatory mediator. Therefore, we aim to explore whether HPGDS could be a therapeutic target in the diabetic wound (DW). Method In this study, we compared gene expression profilings of diabetic human foot skin and non-diabetic human foot skin from the Gene Expression Omnibus database. We detected the characteristics of immune components in diabetic mice wound and investigated the role and underlying mechanism of the differently expressed Hpgds for the diabetic wound healing. For in vivo studies, we engineered ADSC to overexpress Hpgds (ADSCHpgds) and evaluated its effects on diabetic wound healing using a full-thickness skin wound model. For in vitro studies, we evaluated the role of ADSCHpgds conditioned medium and PGD2 on Lipopolysaccharide (LPS) induced macrophage. Results Hpgds was significantly down-regulated in type 2 diabetic mice wound and its deficiency delayed normal wound healing. ADSCHpgds accelerated DW healing by reducing neutrophil and CD8T cell recruitment, promoting M2 macrophage polarization and increasing the production of growth factors. ADSCHpgds conditioned medium showed superior capability in promoting M2 macrophage transition than conditioned medium derived from ADSC alone. Conclusion Our results demonstrated that Hpgds is required for wound healing, and ADSCHpgds could accelerate DW healing by improving anti-inflammatory state and normalizing the proliferation phase of wound healing in mice. These findings provide a new insight in the therapeutic strategy of diabetic wound.

Autologous bone marrow mononuclear cell (BMMNC) transplantation has been widely studied in recent years. The fresh cell cocktail in BMMNCs, without going through the in vitro culture process, helps to establish a stable microenvironment for osteogenesis, and each cell type may play a unique role in bone regeneration. Our study compared the efficacy of concentrated fresh BMMNCs and cultured bone marrow-derived mesenchymal stem cells (BMSCs) in Beagle dogs for the first time. Fifteen-millimeter segmental bone defects were created in the animals' tibia bones. In BMMNCs group, the defects were repaired with concentrated fresh BMMNCs combined with β-TCP (n = 5); in cultured BMSC group, with in vitro cultured and osteo-induced BMSCs combined with β-TCP (n = 5); in scaffold-only group, with a β-TCP graft alone (n = 5); and in blank group, nothing was grafted (n = 3). The healing process was monitored by X-rays and single photon emission computed tomography. The animals were sacrificed 12 months after surgery and their tibias were harvested and analyzed by microcomputed tomography and hard tissue histology. Moreover, the microstructure, chemical components, and microbiomechanical properties of the regenerated bone tissue were explored by multiphoton microscopy, Raman spectroscopy and nanoindentation. The results showed that BMMNCs group promoted much more bone regeneration than cultured BMSC group. The grafts in BMMNCs group were better mineralized, and they had collagen arrangement and microbiomechanical properties similar to the contralateral native tibia bone. These results indicate that concentrated fresh bone marrow mononuclear cells may be superior to in vitro expanded stem cells in segmental bone defect repair.

With the continuous development of bone tissue engineering, the importance of immune response in bone tissue regeneration is gradually recognized. The new bone tissue engineering products should possess immunoregulatory functions, harmonizing the interactions between the bone's immune defense and regeneration systems, and promoting tissue regeneration. This article will interpret the relationship between the bone immune system, bone tissue regeneration, as well as the immunoregulatory function of bone biomaterials and seed stem cells in bone tissue engineering. This review locates arears for foucusing efforts at providing novel designs ideas about the development of immune-mediation targeted bone tissue engineering products and the evaluation strategy for the osteoimmunomodulation property of bone biomaterials.