Conventionally, autogenous bone transplantation is performed for synostosis of bone fracture part, and reconstruction of bone defective part after excision of benign osteoncus and the like, by harvesting bone from own healthy part and transplanting the bone in the bone defective part. However, due to the invasion on a healthy part, complications are developed in a high rate of about 30%, such as infection of and residual pain in the bone donor site, nerve damage near the bone donor site and the like. In a case where the area of synostosis and bone defect are large, a mass of autogenous bone is necessary, the defective autogenous bone donor site may sometimes cause a clinical problem.
To avoid autogenous bone transplantation and compensate for the shortage of autogenous bone amount, an artificial bone using calcium phosphate and β-tricalcium phosphate (β-TCP) has been used. However, since artificial bone itself does not have an osteoinductive capacity, its applicable site is limited to a comparatively small bone defect under good bone formation environment, and since ossification potential is inferior as compared to autogenous bone, it takes some time to obtain dynamic strength, thus problematically requiring load restriction and rest for a long time after operation. With such background, bone formation techniques with osteoinductive capacity applicable to extensive synostosis and bone defect have been widely studied.
In recent years, a technique for culturing own bone marrow mesenchymal stem cells and transplanting the cells into a bone defective part in combination with an artificial bone has been developed and clinical application has been reported (non-patent document 1). However, it lacks broad utility, since various problems are accumulated in that specialized facilities such as clean room where cell culture can be performed (cell processing center) are necessary, which makes it practically difficult for municipal hospitals to employ the technique, mesenchymal cell with multilineage potential has a risk of canceration, differentiation induction is not necessarily perfect and the like.
Moreover, as a bone formation treatment using a growth factor, bone morphogenetic protein-2 (BMP-2) produced by genetic recombination was approved for use in vertebral body fusion by Food and Drug Administration in Europe and the United States in 1997, and is clinically applied in US. In recent years, however, its effectiveness and safety are questioned. For example, a report has documented that, in lumbar interbody fusion using BMP-2, bone resorption of fixed vertebral body and transplanted bone occurred at high frequency to drastically decrease the synostosis rate. In addition, there are reports on inflammatory reaction in lumbar vertebral peripheral tissues by MRI useful for the evaluation of soft tissues, and severe complications such as difficult breathing due to pharyngeal edema, dysphagia and abnormal swelling of cervical part observed in a case of cervical fixing (non-patent documents 2 and 3). The cause thereof is considered to be edematous change in the soft tissue and vital organs resulting from an antigen-antibody reaction induced by administration of a large amount of artificially-produced growth factor which diffused from the administration site to the peripheral tissues. In addition, since BMP-2 is expensive, it adds several hundreds of thousands of yen to the operation cost, producing a financial burden on patients.
Platelet-rich plasma (also referred to as PRP) is a concentrated platelet plasma obtained by removing red blood cell from peripheral blood by centrifugal separation at a low speed. PRP contains a large amount of growth factors such as platelet-derived growth factor (PDGF) contained in platelet, transforming growth factor β (TGF-β), fibroblast growth factor (FGF), insulin-like growth factor (IGF) and the like, and is known to show effects such as angiogenesis, osteogenesis, promotion of wound healing and the like by a synergistic action of these. It has also been confirmed that a combined use of PRP and an appropriate drug delivery system material such as gelatin hydrogel and the like exhibits osteogenetic activity in long bone and skull bone defect models (patent document 1, non-patent documents 4 and 5).
However, the effect of PRP alone is not sufficient to afford sufficient ossification in large bone defect, anatomically unfused bones, and spinal fusion to joint together spinal bones, and a scaffold having a three-dimensional structure that promotes differentiation and induction of osteoblasts is absolutely necessary.