Inhibition of miR-92a enhances fracture healing via promoting angiogenesis in a model of stabilized fracture in young mice.

MicroRNAs (miRNAs) are endogenous small noncoding RNAs regulating the activities of target mRNAs and cellular processes. Although no miRNA has been reported to play an important role in the regulation of fracture healing, several miRNAs control key elements in tissue repair processes such as inflammation, hypoxia response, angiogenesis, stem cell differentiation, osteogenesis, and chondrogenesis. We compared the plasma concentrations of 134 miRNAs in 4 patients with trochanteric fractures and 4 healthy controls (HCs), and the levels of six miRNAs were dysregulated. Among these miRNAs, miR-92a levels were significantly decreased 24 hours after fracture, compared to HCs. In patients with a trochanteric fracture or a lumbar compression fracture, the plasma concentrations of miR-92a were lower on days 7 and 14, but had recovered on day 21 after the surgery or injury. To determine whether systemic downregulation of miR-92a can modulate fracture healing, we administered antimir-92a, designed using locked nucleic acid technology to inhibit miR-92a, to mice with a femoral fracture. Systemic administration of antimir-92a twice a week increased the callus volume and enhanced fracture healing. Enhancement of fracture healing was also observed after local administration of antimir-92a. Neovascularization was increased in mice treated with antimir-92a. These results suggest that plasma miR-92a plays a crucial role in bone fracture healing in human and that inhibition of miR-92a enhances fracture healing through angiogenesis and has therapeutic potential for bone repair.

Effect of titania-based surface modification of polyethylene terephthalate on bone-implant bonding and peri-implant tissue reaction.

Organic polymers can be uniformly surface-modified with bioactive TiO(2) by using a sol-gel method. Titania-based surface-modified polyethylene terephthalate (TiPET) plates and fabric have shown apatite-forming ability in simulated body fluid. Here, we first investigated the bone-bonding ability and mechanical bonding strength between the surface-modified layer and the base material (PET) of TiPET plates in vivo. For clinical applicability, we also examined the bone-bonding ability of TiPET fabric and the effect of titania-based surface modification on peri-implant tissue reactions (e.g. connective tissue capsule formation) in bone in vivo. Solid PET plates and PET fabric were prepared. Test plates and fabric were surface-modified with titania solution by using a sol-gel method. Histological examinations of the plates implanted into rabbit tibiae revealed direct contact between the TiPET plate and the bone. After the detaching test, a considerable amount of bone residue was observed on the surface of the TiPET plate. This result suggests that the mechanical bond strength between surface-modified layer and the base material is stronger than that between newly generated bone and tibia, and indirectly ensures the mechanical stability of the surface-modified layer. Pulling tests and histological examinations of the TiPET fabric revealed its excellent bone-bonding ability and micro-computed tomographic images showed excellent osteoconductive ability of TiPET fabric. The connective tissue capsule was much thinner, with less inflammatory tissue around the TiPET implants than around the control samples. These results indicate that TiPET fabric possesses a mechanically stable surface-modified layer, excellent bone-bonding ability, osteoconductive ability, and biocompatibility in bone.