The multidirectional in-situ osteogenesis pattern based on biomimetic mineralized dual-crosslinked Fibrinogen-GelMA microspheres in the maxillary sinus region

Dental defects in the posterior maxillary region seriously affect facial contours, as well as physiological functions. When bone height in the maxillary posterior region is extremely insufficient, the difficulty of dental prosthodontics is greatly increased. Autogenous bone replacement of exogenous bone grafting materials is often inadequate, resulting in the insufficient alveolar bone height. It is still necessary to study the mechanism of bone regeneration in this region and explore new treatment methods to ensure the quality of bone reconstruction. The development of mesenchymal stem cell (MSCs) biology and bioengineering has greatly advanced the field of regenerative medicine. MSCs from different tissue sources have different biological processes and differentiation abilities. Our previous studies confirmed that MSCs derived from human maxillary sinus membrane (hMSM) can be cultured in vitro. The lamina propria layer derived MSCs (hLMSCs) and periosteum layer derived MSCs (hPMSCs) from hMSM were isolated and expanded using explant cell culture method. In this study, further study about the biological characteristics of hLMSCs and hPMSCs under the three dimensional biomimetic microenviroment based on biomimetic mineralized dual-crosslinked Fibrinogen-GelMA microspheres are compared using RNA sequencing. According to RNA sequencing and subsequent functional verification, Both hLMSCs and hPMSCs were up-regulated the osteo-related signaling pathways, such as TGF-ß signaling pathway. The osteogenetic functions of hLMSCs could be improved by hPMSCs, and the most related signaling pathway pointed to PI3K-AKT signaling pathway. It seems that both hLMSCs and hPMSCs serve as good MSCs potential candidates for bone regeneration. And It also indicates that hLMSCs and hPMSCs are valuable in vitro tools for preclinical studies and future exploration of the origin osteogenesis machenism in maxillary sinus region. Overall design: To discover the biological characteristics of hLMSCs and hPMSCs and evaluate their osteogenic capabilities, we isolated and cultured the two cells in vitro, and processed osteogenic induction on them in the three dimensional biomimetic microenviroment based on biomimetic mineralized dual-crosslinked Fibrinogen-GelMA microspheres . We performed gene expression profiling analysis using data obtained from RNA-seq of hLMSCs and hPMSCs. Each group contained three samples. We then compared the differential expression genes between the RNA-seq data of hLMSCs and hPMSCs-induced hLMSCs, and their osteogenic induced patterns, respectively. Each group contained three samples.