Mineralised collagen regulated the secretion of adrenomedullin by macrophages to activate the PI3K/AKT signalling pathway to promote bone defect repair.

Biomaterials can affect the osteogenic process by regulating the function of macrophages and transforming the bone immune microenvironment. Mineralised collagen (MC) is an artificial bone that is highly consistent to the microstructure of the native osseous matrix. The studies have confirmed that MC can achieve effective regeneration of bone defects, but the potential mechanism of MC regulating osteogenesis is still unclear. This study confirmed that MC regulate the high expression of adrenomedullin (ADM) in macrophages and promote the osteogenic differentiation, proliferation and migration of BMSCs. Moreover, ADM activated the PI3K/Akt pathway, while the inhibition of PI3K/Akt hindered the proliferation, migration and osteogenic differentiation of BMSCs promoted by ADM. Additionally, the rat mandibular defect model confirmed that ADM promote the repair of mandibular defects, and the inhibition of PI3K/Akt pathway hinders the osteogenic effect of ADM. Our study suggests that MC regulates ADM secretion by macrophages, creates an ideal bone immune microenvironment, activates the PI3K/AKT signalling pathway, and promotes osteogenesis.

Inflammation and immunity gene expression profiling of macrophages on mineralized collagen.

Mineralized collagen (MC) is a biomaterial that is commonly used in the treatment of bone defects. However, the inflammatory response after biomaterial implantation is a recurrent problem that requires urgent attention. Our previous studies on MC-macrophage interactions were descriptive but we did not perform an in-depth analysis on a genetic level to investigate the underlying mechanisms. In this study, we cultured RAW264.7 cells on MC or collagen and examined the proliferation of the macrophages by Cell Counting Kit-8 assay. We sequenced the RNA of the cultured cells to discover differential gene expression patterns and found that a total of 1183 genes were differentially expressed between the MC- and collagen-cultured groups, of which 396 genes were upregulated and 787 were downregulated. Gene ontology analysis revealed that biological processes in MC-cultured cells, such as inflammation and innate immunity, were downregulated; whereas nucleosome assembly, megakaryocyte differentiation, and chromatin assembly were upregulated. We identified several pathways associated with immunity that were significantly enriched using the Kyoto Encyclopedia of Genes and Genomes. Furthermore, we validated the differentially expressed genes from RNA sequencing by quantitative real-time polymerase chain reaction. This study provides insight into the macrophage phenotype based on the microenvironment, which is the foundation for the clinical application of MC-based interventions.

Corrigendum to: Enhancement of BMP-2 and VEGF Carried by Mineralized Collagen for Mandibular Bone Regeneration.

[This corrects the article DOI: 10.1093/rb/rbaa022.].

Enhancement of BMP-2 and VEGF carried by mineralized collagen for mandibular bone regeneration.

Repairing damage in the craniofacial skeleton is challenging. Craniofacial bones require intramembranous ossification to generate tissue-engineered bone grafts via angiogenesis and osteogenesis. Here, we designed a mineralized collagen delivery system for BMP-2 and vascular endothelial growth factor (VEGF) for implantation into animal models of mandibular defects. BMP-2/VEGF were mixed with mineralized collagen which was implanted into the rabbit mandibular. Animals were divided into (i) controls with no growth factors; (ii) BMP-2 alone; or (iii) BMP-2 and VEGF combined. CT and hisomputed tomography and histological staining were performed to assess bone repair. New bone formation was higher in BMP-2 and BMP-2-VEGF groups in which angiogenesis and osteogenesis were enhanced. This highlights the use of mineralized collagen with BMP-2/VEGF as an effective alternative for bone regeneration.