Promoting osteoblast proliferation on polymer bone substitutes with bone-like structure by combining hydroxyapatite and bioactive glass

Abstract

Mimicking the structural features of natural bone has been demonstrated to bring pronounced advantages for mechanical reinforcement of polymeric orthopedic substitutes that are composed of bioinert polymer matrix and bioactive fillers. However, to trigger effective bone formation and implant integration, the bioactivity of bone substitutes plays a vital role. We hypothesized that the use of hydroxyapatite (HA) and bioactive glass (BG), compared to the use of HA alone, could improve the biological properties of polymer-based bone substitutes. Herein, high-density polyethylene (PE) composites loaded with HA and BG were fabricated using a modified injection molding machine that can provide intense shear flow to regulate the hierarchical structure of the composites. Morphological observation revealed that bone-like structures were formed in both HA/PE and BG/HA/PE composites, showing highly oriented interlocked shish kebabs. In addition, the bioactive fillers were distributed uniformly. Osteoblast proliferation was promoted by the combination of HA and BG. The mechanism was the upregulation of Runx2 expression (1.51 ± 0.17) with BG and the activation of the TAZ/YAP (1.41/0.64) signaling pathway, which accelerated the generation of ossification-related proteins. BG can regulate microRNA to promote the mRNA expression of Runx2. The silencing of Runx2 expression can inhibit BG-induced osteoblast proliferation. These results suggest that the BG/HA/PE composites having a bone-like structure have high potential as bone substitutes to repair large bone defects.

Keywords: Bioactive glass; Bone substitute; Bone-like structure; Hydroxyapatite; Osteoblast proliferation.