Effect of Single Injection of Recombinant Human Bone Morphogenetic Protein-2-Loaded Artificial Collagen-Like Peptide in a Mouse Segmental Bone Transport Model.

Ryo Tazawa,Terumasa Matsuura,Hiroaki Minehara,Wataru Saito,Gen Inoue,Kentaro Uchida,Masashi Takaso,Tadashi Kawamura

doi:10.1155/2019/1014594

Ryo Tazawa, Terumasa Matsuura + Show 6 more

Open Access

https://doi.org/10.1155/2019/1014594

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Journal: BioMed research international	Publication Date: Dec 23, 2019
Citations: 2	License type: CC BY 4.0

Affiliation: Kitasato University

Abstract

This study aimed to investigate whether a single injection of recombinant human bone morphogenetic protein-2-loaded artificial collagen-like peptide gel (rhBMP-2/ACG) accelerates consolidation at the bone defect site and bone union at the docking site in a mouse segmental bone transport (SBT) model. A critical sized bone defect (2 mm) was created in the femur of mice and subsequently reconstructed using SBT with an external fixator. Mice were divided into four treatment groups: Group CONT (immobile control), Group 0.2 (bone segments moved 0.2 mm/day for 10 days), Group 1.0 (bone segments moved 1.0 mm/day for 2 days), and Group 1.0/BMP-2 (rhBMP-2/ACG injected into the bone defect and segments moved 1.0 mm/day for 2 days). Consolidation at the bone defect site and bone union at the docking site was evaluated radiologically and histologically across eight weeks. Bone volume and bone mineral content were significantly higher in Group 0.2 than in Group 1.0. Group 0.2 showed evidence of rebuilding of the medullary canal eight weeks after surgery at the bone defect site. However, in Group 1.0, maturation of regenerative bone at the bone defect site was poor, with the central area between the proximal and distal bone composed mainly of masses of fibrous and adipose tissue. Group 1.0/BMP-2 had higher bone volume and bone mineral content compared to Group 1.0, and all mice achieved bone union at the bone defect and docking sites. Single injection of rhBMP-2/ACG combined with SBT may be effective for enhancing bone healing in large bone defects.

Highlights

Surgical treatment of large bone defects has long been a challenge for orthopaedic surgeons
We investigated whether a single injection of rhBMP-2-loaded artificial collagen-like peptide gel accelerates consolidation at the bone defect site and bone union at the docking site in a mouse Segmental bone transport (SBT) model
Our preliminary study showed that 2.0 μg of rhBMP-2 without poly(POG)n failed to promote bone formation in a mice bone defect model. erefore, to administer and retain rhBMP-2 at the bone defect site, we dissolved 2.0 μg of rhBMP-2 in 22.5 μL of the collagen-like polypeptide poly(POG)n gel, which was purchased from JNC Corporation (Tokyo, Japan)

Summary

Introduction

Surgical treatment of large bone defects has long been a challenge for orthopaedic surgeons. Segmental bone transport (SBT) using an external fixator is a standard treatment for large-diameter bone defects at the donor site with low morbidity [1]. Erefore, strategies that reduce the treatment time and improve new bone formation using SBT without the need for secondary surgery are necessary for the treatment of large bone defects. Successful SBT treatment depends on both bone regeneration at the bone defect site, called the “regenerate,” and bone union at the meeting point between the transported and distal segments at the completion of bone transport, called the “docking site.”. Studies aimed at improving the bone healing process in SBT have revealed that regeneration at the defect site is improved by the optimization of transport speed [3, 4]. Nonunion at the docking site often occurs [5,6,7], even when consolidation is successfully achieved using an optimized transport speed

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