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

  • PDF / 3,207,791 Bytes
  • 7 Pages / 595.276 x 790.866 pts Page_size
  • 52 Downloads / 179 Views

DOWNLOAD

REPORT


(2020) 15:471

RESEARCH ARTICLE

Open Access

Poly(POG)n loaded with recombinant human bone morphogenetic protein-2 accelerates new bone formation in a critical-sized bone defect mouse model Ryo Tazawa1, Kentaro Uchida1,2* , Hiroaki Minehara1, Terumasa Matsuura1, Tadashi Kawamura1, Hiroyuki Sekiguchi2, Kyoko Muneshige1, Sho Inoue1, Gen Inoue1 and Masashi Takaso1

Abstract Background: Delivery 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. Methods: A 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. Results: Administration 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. Conclusions: Our 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. Keywords: Collagen-like peptides, Poly(POG)n, Bone defect, New bone formation, Bone morphogenetic protein-2

Background There are significant clinical limitations to the rebuilding of large bone segments following extensive bone loss as result of pathological events including trauma, inflammation, and surgical treatment of tumors. Recombinant human (rh) bone morphogenetic protein (BMP)-2 has * Correspondence: [email protected] 1 Department of Orthopaedic Surgery, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara City, Kanagawa 252-0374, Japan 2 Shonan University of Medical Sciences Research Institute, Nishikubo 500, Chigasaki City, Kanagawa 253-0083, Japan

immense potential in clinical applications. However, it has a short half-life, is expensive, and is associated with the risk of heterotopic ossification [1–6]. Therefore, the development of a carrier is needed for the retention of rhBMP-2 to enhance bone formation and reduce side effects in clinical settings. 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 [7–10]. ACS/rhBMP-2 is

© The Author(s). 2020 Open Access This article is licensed under a Creative Commons At