In situ-formed hyaluronan gel/BMP-2/hydroxyapatite composite promotes bone union in refractory fracture model mice

Article type: Research Article

Authors: Saito, Hiroki^a | Shoji, Shintaro^a | Kuroda, Akiyoshi^a | Inoue, Gen^a | Tazawa, Ryo^a | Sekiguchi, Hiroyuki^b | Fukushima, Kensuke^a | Miyagi, Masayuki^a | Takaso, Masashi^a | Uchida, Kentaro^{a; b;}

Affiliations: [a] Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Japan | [b] Shonan University of Medical Sciences Research Institute, Chigasaki City, 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 8111, Fax: +81 42 778 8111; E-mail: kuchida@med.kitasato-u.ac.jp

Abstract: BACKGROUND:A combination of synthetic porous materials and BMP-2 has been used to promote fracture healing. For bone healing to be successful, it is important to use growth factor delivery systems that enable continuous release of BMP-2 at the fracture site. We previously reported that in situ-formed gels (IFGs) consisting of hyaluronan (HyA)-tyramine (TA), horseradish peroxidase and hydrogen peroxide enhance the bone formation ability of hydroxyapatite (Hap)/BMP-2 composites in a posterior lumbar fusion model. OBJECTIVE:We examined the effectiveness of IFGs-HyA/Hap/BMP-2 composites for facilitating osteogenesis in refractory fracture model mice. METHODS:After establishing the refractory fracture model, animals were either treated at the site of fracture with Hap harboring BMP-2 (Hap/BMP-2) or IFGs-HyA with Hap harboring BMP-2 (IFGs-HyA/Hap/BMP-2) (n = 10 each). Animals that underwent the fracture surgery but did not receive any treatment were considered the control group (n = 10). We determined the extent of bone formation at the fracture site according to findings on micro-computed tomography and histological studies four weeks following treatment. RESULTS:Animals treated with IFGs-HyA/Hap/BMP-2 demonstrated significantly greater bone volume, bone mineral content and bone union than those treated with vehicle or IFG-HyA/Hap alone. CONCLUSIONS:IFGs-HyA/Hap/BMP-2 could be an effective treatment option for refractory fractures.

Keywords: In situ-formed gels, hydroxyapatites, hyaluronic acid, bone morphogenetic protein, refractory fracture

DOI: 10.3233/BME-230021

Journal: Bio-Medical Materials and Engineering, vol. 34, no. 6, pp. 537-544, 2023