Acceleration of bone union by in situ-formed hydrogel containing bone morphogenetic protein-2 in a mouse refractory fracture model

Abstract

Background An 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. Methods Immediately 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). Results Fracture 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). Conclusion IFH-HA/BMP-2 may contribute to the treatment of refractory fractures.

Effect of Bone Morphogenetic Protein-2 (BMP-2)/Hydroxyapatite/In Situ-Formed Hyaluronan Hydrogel Composites on Bone Formation in a Murine Model of Posterolateral Lumbar Fusion

“…In a previous study, an IFH-HA material that was capable of continually releasing platelet-derived growth factors over 14 days enhanced the proliferation of MPCs in vitro [ 25 ]. Likewise, in our previous study, IFH-HA was able to continually release BMP2 for 14 days in vitro [ 18 ]. Together, the present study and previous studies suggest that BMP2/HAP/IFH-HA composites may exhibit high bone induction potential owing to their ability to continually release BMP-2.…”

“…We generated the hyaluronan-tyramine (HA-TA) conjugate based on details described elsewhere [ 18 ]. To synthesize IFH-HA, the HA-TA polymer was crosslinked in the presence of the catalyzing enzyme HRP (FUJIFILM Wako Pure Chemical Corporation, Richmond, VA) and H 2 O 2 in 10 mM phosphate-buffered saline (PBS; pH 7.4).…”

“…IFHs cure via an oxidative coupling reaction between hydrogen peroxide (H 2 O 2 ) and horseradish peroxidase (HRP) in an aqueous solution. In our previous studies, we reported that IFH constructed from HA (IFH-HA) enabled a sustained release of BMP-2 at a fracture and bone defect site [ 18 , 19 ]. However, the effect of combining BMP-2 with CaP remains unclear.…”

BMP‐2/TGF‐β1 gene insertion into ligament‐derived stem cells sheet promotes tendon–bone healing in a mouse

“…BMP‐2, a potent osteoinductive cytokine, can induce osteogenic and chondrogenic formation. [ 10 ] BMP‐2 promotes early bone growth around tunnels, allowing the tendon–bone to heal more quickly. [ 5,11 ] Dong et al.…”

Investigation of the medium-term effect of osteoprotegerin/bone morphogenetic protein 2 combining with collagen sponges on tendon-bone healing in a rabbit

“…11 Additionally, the osteoinductive cytokine BMP-2 induces the formation of bones and cartilage. 15 Therefore, incorporating BMP-2 binding peptides into the materials used for ACLR enhances bone formation in the femoral tunnels, thereby improving graft quality. 16 A collagen sponge (CS) is a biomaterial that can deliver intrinsic signals within the structure to enhance tissue formation and be degraded by the body when new tissue is formed.…”