Platelet-Activating Biominerals Enhanced Injectable Hydrogels With Superior Bioactivity for Bone Regeneration.

Xin Chen,Yunshan Fan,Zhengran Ying,Jiajun Yan,Yingying Jiang,Feng Chen,Shuo Tan,Shisheng He,Zhi Zhou,Junjian Liu

doi:10.3389/fbioe.2022.826855

Abstract

Refractory bone fracture, which is difficult to be treated, is a common clinical disease. Taking inspiration from the natural process of bone regeneration, we provide a biomimetic strategy to develop a new injectable biomaterial for repairing bone defects, which is mainly composed of platelets, fibrins, and biominerals. Biomineral nanoparticles (EACPNs) with an amorphous phase are prepared by an enzyme-catalyzed route and display a platelet-activating property. The composite hydrogel (EPH) of EACPNs, fibrins, and platelets is injectable, and has similar chemical properties to natural materials in bone regeneration. The dried EPH samples display a highly porous structure, which would be favorable for cell attachment and growth. The results from in vitro studies indicate that EPH has high biocompatibility and superior bioactivity in promoting the osteogenic differentiation of rat bone marrow stem cells (rBMSCs). Furthermore, the results from in vivo studies clearly indicate that EPH can induce the formation of new collagen and vessels in the defect area, thus leading to faster regeneration of bone defects at 2 weeks. Our study provides a strategy for designing new biomimetic materials, which may be favorable in the treatment of refractory bone fracture.

Highlights

Refractory bone fracture disease is a constant problem among orthopedic patients in hospitals that leads to a serious impact on the health and quality of life
The scanning electron microscopy (SEM) micrographs (Figures 1D,E) of EACPNs display a spherical morphology, which is consistent with the transmission electron microscopy (TEM) results
The alkaline phosphatase (ALP) enzyme acts as a cleaver to hydrolyze phosphate ions, which react with calcium ions to form EACPNs from ATP molecules

Summary

INTRODUCTION

Refractory bone fracture disease is a constant problem among orthopedic patients in hospitals that leads to a serious impact on the health and quality of life. Through the understanding of the bone formation process, we think that the combined use of calcium phosphate-based biominerals with natural constituents in bone regeneration may provide a new strategy to design functional biomaterials. We developed a strategy to prepare injectable composite hydrogels for bone defect repair by combining the use of EACBN biominerals and platelets. To evaluate whether the ACPN–platelet composite hydrogel has the ability to induce chemotaxis of cells, human umbilical vein endothelial cells (HUVECs, Cell Bank of the Chinese Academy of Sciences, Shanghai, China) were seeded into a 6-well plate at a concentration of 2×104 cells per well and co-cultured with the extracted supernatant of FH, PH, and EPH (at 24 h). To assess the ALP activity of the supernatant-treated rBMSCs at Days 7 and 14, the co-cultured cells were washed with PBS, fixed in 4% paraformaldehyde for 20 min and stained with an Alkaline Phosphatase Kit (Beyotime Biotechnology, Shanghai, China). When *p < 0.05, **p < 0.01, and ***p < 0.001, the difference was regarded as statistically significant

RESULTS AND DISCUSSION

CONCLUSION

ETHICS STATEMENT