The Investigation of LRP5-Loaded Composite with Sustained Release Behavior and Its Application in Bone Repair

Yanhai Xi,Tingwang Jiang,Ning Xu,Xiaojian Ye,Weiheng Wang,Jiangming Yu,Mintao Xue,Jiankun Wen,Hailong He

doi:10.1155/2019/1058410

Abstract

Low-density lipoprotein receptor-related protein 5 (LRP5) plays a vital role in bone formation and regeneration. In this study, we developed an injectable and sustained-release composite loading LRP5 which could gelatinize in situ. The sustained release of the composite and its efficacy in bone regeneration were evaluated. Sodium alginate, collagen, hydroxyapatite, and LRP5 formed the composite LRP5-Alg/Col/HA. It was found that the initial setting time and final setting time of LRP5-Alg/Col/HA containing 4% alginate were suitable for surgical operation. When the composite was loaded with 40 μg/mL LRP5, LRP5-Alg/Col/HA did not exhibit a burst-release behavior and could sustainably release LRP5 up to 21 days. Up to 18 days, LRP5 released from LRP5-Alg/Col/HA still present the binding activity with DKK1 (Wnt signaling pathway antagonist) and could increase the downstream β-catenin mRNA in bone marrow mesenchymal stem cells. Moreover, LRP5-Alg/Col/HA was found to significantly increase bone mineral density in the defect area after 6 weeks’ implantation of LRP5-Alg/Col/HA into the rats’ calvarial defect area. H&E staining detection demonstrated that LRP5-Alg/Col/HA could mediate the formation of a new bone tissue. Therefore, we concluded that Alg/Col/HA was a suitable sustained-release carrier for LRP5 and LRP5-Alg/Col/HA had a significant effect on repairing bone defects and could be a good bone regeneration material.

Highlights

With the development of society and the consequent industrial accidents, traffic accidents, and natural disasters, the number of patients with orthopedic trauma has increased
The injectable bone repair material can be implanted into the body by injection with insignificant trauma, eliminating many complications associated with traditional bone transplantation surgery
The biological activity of lipoprotein receptor-related protein 5 (LRP5) in the conditioned mediums collected at different times was indirectly evaluated by the expression level of the downstream gene β-catenin of the rat bone marrow-derived stem cells (MSCs)

Summary

Introduction

With the development of society and the consequent industrial accidents, traffic accidents, and natural disasters, the number of patients with orthopedic trauma has increased. The injectable bone repair material can be implanted into the body by injection with insignificant trauma, eliminating many complications associated with traditional bone transplantation surgery It has good plasticity, which can fill bone defects of any shape or size, and can be gelatinized by physical or chemical action-mediated sol-gel phase transformation, forming a scaffold material with porous microstructure and exerting bone conduction [4, 5]. According to Tan’s report [16], a gel-like composite containing alginate, collagen, and hydroxyapatite (HA) is prepared with sustained-release and injectable properties. Alginate hydrogel can be combined with collagen and hydroxyapatite to prepare a gel composite suitable for bone tissue repair. A peptide derived from an LRP5 gene enhances stem cell aggregation and chondrogenic differentiation [24] This effect is mainly through the Wnt signaling pathway. After loading with LRP5, the sustained-release capability, biocompatibility, and repair of bone defects in vivo were studied

Method

Results and Discussion

Conclusion