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There is an increasing demand for biomaterials with skull regeneration for clinical application. However, most of the current skull repair materials still have limitations, such as inadequate sources, poor cell adherence, differentiation, tissue infiltration, and foreign body sensation. Therefore, this study developed porous microsphere-based scaffolds containing mouse embryonic osteoblast precursor cells (MC3T3-E1 cells) and calcitriol (Cal) using gelatin and gelatin/hydroxyapatite through green freeze-crosslinking and freeze-drying. Gelatin was employed to prepare porous microspheres with a particle size of 100-300 μm, containing open pores of 2-70 μm and interconnected paths. Furthermore, the addition of Cal to porous gelatin microsphere-based scaffolds containing MC3T3-E1 cells (PGMSs-MC) and porous gelatin/hydroxyapatite composite microspheres containing MC3T3-E1 cells (HPGMSs-MC) improved their osteoinductivity and cell proliferation and promoted the formation of mature and well-organized bone. The developed Cal-HPGMSs-MC and Cal-PGMSs-MC displayed a good porous structure and cytocompatibility, histocompatibility, osteoconductivity, and osteoinduction. Thus, the designed scaffolds provide a promising prospect for tissue-engineered constructs with skull growth and integration, laying a foundation for further research on the reconstruction of skull defects., (Copyright © 2022. Published by Elsevier B.V.)

Gelatin has various attractive features as biomedical materials, for instance, biocompatibility, low immunogenicity, biodegradability, and ease of manipulation. In recent years, various gelatin-based microspheres (GMSs) have been fabricated with innovative technologies to serve as sustained delivery vehicles of drugs and genetic materials as well as beneficial bacteria. Moreover, GMSs have exhibited promising potentials to act as both cell carriers and 3D scaffold components in tissue engineering and regenerative medicine, which not only exhibit excellent injectability but also could be integrated into a macroscale construct with the laden cells. Herein, we aim to thoroughly summarize the recent progress in the preparations and biomedical applications of GMSs and then to point out the research direction in future. First, various methods for the fabrication of GMSs will be described. Second, the recent use of GMSs in tumor embolization and in the delivery of cells, drugs, and genetic material as well as bacteria will be presented. Finally, several key factors that may enhance the improvement of GMSs were suggested as delivery vehicles. • Various existing methods for the fabrication of gelatin-based microspheres (GMSs); • Recent uses of GMSs in delivery of cells, drugs, and genetic material as well as bacteria; • Applications of GMSs in tumor embolization; • The key factors and advantages of GMSs as delivery vehicles. [ABSTRACT FROM AUTHOR]