Acceleration of bone formation using in situ-formed hyaluronan-hydrogel containing bone morphogenetic protein-2 in a mouse critical size bone defect model

Article type: Research Article

Authors: Shoji, Shintaro^a | Uchida, Kentaro^{a; b;} | Tazawa, Ryo^a | Saito, Wataru^a | Kuroda, Akiyoshi^a | Sekiguchi, Hiroyuki^{a; b} | Ishii, Daisuke^a | Inoue, Sho^a | Inoue, Gen^a | Takaso, Masashi^a

Affiliations: [a] Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan | [b] Shonan University of Medical Sciences Research Institute, Chigasaki, Kanagawa, Japan

Correspondence: [*] Corresponding author: Kentaro Uchida, Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa 252-0374, Japan; and Shonan University of Medical Sciences Research Institute, Nishikubo 500, Chigasaki City, Kanagawa 253-0083, Japan. Tel.: +81 42 778 9217; Fax: +81 42 778 9217; E-mail: kuchida@med.kitasato-u.ac.jp

Abstract: BACKGROUND:An enzymatic crosslinking strategy using hydrogen peroxide and horseradish peroxidase is receiving increasing attention for application with in situ-formed hydrogels (IFHGs). IFHGs may also be ideal carrier materials for bone repair, although their ability to carry bone morphogenetic protein-2 (BMP2) has yet to be examined. OBJECTIVE:We examined the effectiveness of an IFHG made of hyaluronan (IFHG-HA) containing BMP2 for promoting bone formation in a mouse critical size bone defect model. METHODS:C57/BL6J mice received a 2-mm femoral critical-sized bone defect before being randomly assigned to one of the following treatment groups (n = 6): control (no treatment), IFHG-HA only, PBS with BMP2, and IFHG-HA with BMP2. X-ray radiographs were utilized to track new bone formation, and micro-computed tomography and histological examination were performed on new bone formed at the bone defect site two weeks after surgery. RESULTS:Mice treated with PBS with BMP2 and IFHG-HA with BMP2 had greater bone volume (BV) and bone mineral content (BMC) than those receiving control, and successfully achieved consolidation. Mice treated with IFHG-HA with BMP2 had significantly higher BV and BMC than those treated with PBS with BMP2. CONCLUSIONS:IFHG-HA may be an effective carrier for BMP2 to enable delivery for bone defect repair.

Keywords: In situ-formed hydrogels, bone defect, carrier, bone morphogenetic protein-2

DOI: 10.3233/BME-201172

Journal: Bio-Medical Materials and Engineering, vol. 32, no. 4, pp. 207-215, 2021