Highly Open Porous Gelatin Microspheres with MC3T3-E1 Cells for the Repair of Skull Defect

To address nondegradable or slowly degradable scaffolds for open skull surgery, microspheres (MSs)-based cell scaffolds have been used to repair skull defects. However, most MSs-based cell scaffolds show poor cell adherence, differentiation and tissue infiltration. Consequently, gelatin, a macromolecular hydrophilic colloid, has been employed to prepare highly open porous microspheres with particle sizes of 100–300 µm. Highly open porous gelatin microspheres (HOPG-MSs) have 2–70 µm of open pores and interconnected paths. HOPG-MSs has the advantage of MSs and scaffolds, and could be used as a carrier for osteoblast transplantation. In addition to convenient transplantation into defective tissue and in contrast to the poor performances of covalently crosslinked gelatin microspheres (CCG-MSs) and open porous gelatin/hydroxyapatite composite microspheres (HA-OPG-MSs), HOPG-MSs present suitable surface pores and interconnected passages, thereby promoting cell adhesion and cell proliferation in vitro, and improving the differentiation of mouse embryonic osteoblast precursor cells (MC3T3-E1 cells). HOPG-MSs also greatly promote osteoblast regeneration compared with traditional CCG-MSs and HA-OPG-MSs in ectopic bone formation mouse models. HOPG-MSs can not only absorb nutrients from outside the scaffold but also protect cells during transplantation so that more live cells are allowed to proliferate and migrate to the damaged tissue. The results of this study suggest that cell-laden HOPG-MSs scaffolds can promote bone growth and integration, laying a foundation for further research on the reconstruction of skull defects. Funding: This work was supported by the National Natural Science Foundation of China, China (Grant No. 21604045, 81671305 and 81470059), the Natural Science Foundation of Shandong Province, China (Grant No. ZR2016BQ36), the Applied Basic Research Program of Qingdao, China (Grant No. 16-5-1-91-jch). Declaration of Interest: None to declare. Ethical Approval: The in vivo study was approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University, and under its guidance, all animal experiments were carried out.