Engineered Chimeric Peptides with IGF-1 and Titanium-Binding Functions to Enhance Osteogenic Differentiation In Vitro under T2DM Condition

Abstract

Due to the complexity of the biomolecules and titanium (Ti) combination, it is a challenge to modify the implant surface with biological cytokines. The study proposed a new method for immobilizing cytokines on implant surface to solve the problem of low osseointegration under type 2 diabetes mellitus (T2DM) condition. This new modified protein that connected Ti-binding artificial aptamer minTBP-1 with Insulin-like growth factor I (IGF-I), had a special strong affinity with Ti and a therapeutic effect on diabetic bone loss. According to the copies of minTBP-1, three proteins were prepared, namely minTBP-1-IGF-1, 2minTBP-1-IGF-1 and 3minTBP-1-IGF-1. Compared with the other modified proteins, 3minTBP-1-IGF-1 adsorbed most on the Ti surface. Additionally, this biointerface demonstrated the most uniform state and the strongest hydrophilicity. In vitro results showed that the 3minTBP-1-IGF-1 significantly increased the adhesion, proliferation, and mineralization activity of osteoblasts under T2DM conditions when compared with the control group and the other modified IGF-1s groups. Real-time PCR assay results confirmed that 3minTBP-1-IGF-1 could effectively promote the expression of osteogenic genes, that is, ALP, BMP-2, OCN, OPG, and Runx2. All these data indicated that the 3minTBP-1-IGF-1 had the most efficacious effect in promoting osteoblasts osteogenesis in diabetic conditions, and may be a promising option for further clinical use.