Poly(POG)n loaded with recombinant human bone morphogenetic protein-2 accelerates new bone formation in a critical-sized bone defect mouse model

Ryo Tazawa,Kentaro Uchida,Terumasa Matsuura,Masashi Takaso,Tadashi Kawamura,Gen Inoue,Kyoko Muneshige,Hiroaki Minehara,Sho Inoue,Hiroyuki Sekiguchi

doi:10.1186/s13018-020-01977-z

Abstract

BackgroundDelivery of bone morphogenetic protein-2 (BMP-2) via animal-derived absorbable collagen materials is used for the treatment of large bone defects. However, the administration of bovine proteins to humans is associated with the risk of zoonotic complications. We therefore examined the effect of combining BMP-2 with collagen-like peptides, poly(POG)n, in a critical-sized bone defect mouse model.MethodsA 2-mm critical-sized bone defect was created in the femur of 9-week-old male C57/BL6J mice. Mice were randomly allocated into one of four treatment groups (n = 6 each): control (no treatment), poly(POG)n only, 0.2 μg, or 2.0 μg BMP-2 with poly(POG)n. New bone formation was monitored using soft X-ray radiographs, and bone formation at the bone defect site was examined using micro-computed tomography and histological examination at 4 weeks after surgery.ResultsAdministration of 2.0 μg of BMP-2 with poly(POG)n promoted new bone formation and resulted in greater bone volume and bone mineral content than that observed in the control group and successfully achieved consolidation. In contrast, bone formation in all other groups was scarce.ConclusionsOur findings suggest the potential of BMP-2 with poly(POG)n as a material, free from animal-derived collagen, for the treatment of large bone defects.

Highlights

Delivery of bone morphogenetic protein-2 (BMP-2) via animal-derived absorbable collagen materials is used for the treatment of large bone defects
We investigated the efficacy of Recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with a gel formed by poly(POG)n, which is free from animal-derived collagen, in a critical-sized bone defect mouse model
In group BMP(2.0), a weak shadow of new bone was observed at the bone defect site at 2 weeks after surgery, and marked new bone formation was confirmed at 4 weeks after surgery (Fig. 1k, l)

Summary

Introduction

Delivery of bone morphogenetic protein-2 (BMP-2) via animal-derived absorbable collagen materials is used for the treatment of large bone defects. We examined the effect of combining BMP-2 with collagen-like peptides, poly(POG)n, in a critical-sized bone defect mouse model. Recombinant human (rh) bone morphogenetic protein (BMP)-2 has Absorbable collagen sponge (ACS), derived from bovine collagen type I, has been developed to increase the retention of rhBMP-2, and a ACS/rhBMP-2 composite has been shown to accelerate bone healing in bone defects in several animal models [7,8,9,10]. There is no risk of zoonotic complications with non-animal-derived collagen-like peptides. These characteristics indicate that poly(POG)n may be a suitable alternative to ACS as a carrier for BMP-2, the efficacy of poly(POG)n gels as a carrier for rhBMP-2 in the treatment of bone defects remains to be determined

Methods

Results

Discussion

Conclusion