Abstract
BackgroundAn enzymatic crosslinking strategy using hydrogen peroxide and horseradish peroxidase is receiving increasing attention for application with in situ-formed hydrogels (IFHs). Several studies have reported the application of IFHs in cell delivery and tissue engineering. IFHs may also be ideal carrier materials for bone repair, although their potential as a carrier for bone morphogenetic protein (BMP)-2 has yet to be examined. Here, we examined the effect of an IFH made of hyaluronic acid (IFH-HA) containing BMP-2 in promoting osteogenesis in a mouse refractory fracture model.MethodsImmediately following a fracture procedure, animals either received no treatment (control) or an injection of IFH-HA/PBS or IFH-HA containing 2 μg BMP-2 (IFH-HA/BMP-2) into the fracture site (n = 16, each treatment).ResultsFracture sites injected with IFH-HA/BMP-2 showed significantly greater bone volume, bone mineral content, and bone union compared with sites receiving no treatment or treated with IFH-HA/PBS alone (each n = 10). Gene expression levels of osteogenic markers, Alpl, Bglap, and Osx, were significantly raised in the IFH-HA/BMP-2 group compared to the IFH-HA/PBS and control groups (each n = 6).ConclusionIFH-HA/BMP-2 may contribute to the treatment of refractory fractures.
Highlights
An enzymatic crosslinking strategy using hydrogen peroxide and horseradish peroxidase is receiving increasing attention for application with in situ-formed hydrogels (IFHs)
Compared to sites that received no treatment or treated with IFH-hyaluronic acid (HA) alone, fracture sites injected with IFH made of hyaluronic acid (IFH-HA)/Bone morphogenetic protein-2 (BMP-2) showed significantly greater bone volume and bone mineral content (P < 0.05)
Expression of Alkaline phosphatase (Alpl), Bglap, and Osx Gene expression levels of osteogenic makers, Alpl, Bglap, and Osx, were significantly raised in the IFHHA/bone morphogenetic protein (BMP)-2 group compared to the IFH-HA and control groups (Fig. 5a, b, c; P < 0.05)
Summary
An enzymatic crosslinking strategy using hydrogen peroxide and horseradish peroxidase is receiving increasing attention for application with in situ-formed hydrogels (IFHs). We examined the effect of an IFH made of hyaluronic acid (IFH-HA) containing BMP-2 in promoting osteogenesis in a mouse refractory fracture model. 5 to 10% of fractures show poor healing because of delayed or non-union at the fracture site [1, 2]. When this arises, functional disabilities can result due to complications including pseudoarthrosis and skeletal deformities [3]. One method used to increase the speed of fracture healing involves local application of growth factors [4,5,6]. Growth factor delivery systems that sustain the release of BMP-2 at fracture sites are
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