To create a drug delivery system that allows the controlled release of
proteins, such as
growth factors, over a long-term period, cholesteryl group- and acryloyl group-bearing
pullulan (CHPOA)
nanogels were aggregated to form fast-degradable
hydrogels (CHPOA/
hydrogels) by cross-linking with
thiol-bearing
polyethylene glycol. The gold standard of clinical bone reconstruction
therapy with a physiologically active material is treatment with recombinant human
bone morphogenetic protein 2 (BMP2); however, this approach has limitations, such as
inflammation, poor cost-efficiency, and varying interindividual susceptibility. In this study, two distinct
growth factors, BMP2 and recombinant human
fibroblast growth factor 18 (FGF18), were applied to a critical-size skull bone defect for bone repair by the CHPOA/
hydrogel system. The CHPOA-FGF18/
hydrogel displayed identical results to the control CHPOA-PBS/
hydrogel, and the CHPOA-BMP2/
hydrogel treatment imperfectly induced bone repair. By contrast, the CHPOA-FGF18 + BMP2/
hydrogel treatment strongly enhanced and stabilized the BMP2-dependent bone repair, inducing osteoprogenitor cell infiltration inside and around the
hydrogel. This report indicates that the CHPOA/
hydrogel system can successfully deliver two different
proteins to the bone defect to induce effective bone repair. The combination of the CHPOA/
hydrogel system with the
growth factors FGF18 and BMP2 might be a step towards efficient bone tissue engineering.