Abstract
A recent study reported that heat stress stimulates osteogenesis in an in vivo rat model using alginate gel and magnetite cationic liposomes. However, for clinical use, the efficacy for promoting osteogenesis needs to be investigated using clinically approved materials, and preferably with animals larger than rats. The aim of this study was to evaluate multiple heat stimuli-triggered osteogenesis in rat tibial defect models using already clinically applicable materials (Resovist® and REGENOS®) and determine the efficacy also in the rabbit. Fifty-eight rats and 10 rabbits were divided into two groups, respectively, with or without hyperthermia treatment at 45°C for 15 min. (hyperthermia; 20 rats once a week, 8 rats three times a week, 5 rabbits once a week, control; 30 rats and 5 rabbits). Micro-CT assessment at 4 weeks revealed that a significantly stimulated osteogenesis was observed in the once a week group of both rats and rabbits as compared to the control group (p = 0.018 and 0.036, respectively). In contrast, the three times a week group did not show enhanced osteogenesis. Histological examination and image analysis showed consistent results in which the area of mineralized bone formation in the once a week hyperthermia group was significantly increased compared with that in the control group at four weeks (rat; p = 0.026, rabbit; p = 0.031). Newly formed bone was observed in the grafted materials from the periphery toward the center, and more osteoclasts were found in the once a week group. Heat stress also induced enhanced alkaline phosphatase expression in cultured osteoblastic cells, MC3T3, in vitro (p = 0.03). On the other hand, heat stress had no obvious effects on chondrogenic differentiation using ATDC5 cells. Our study demonstrates that heat-stimuli with clinically applicable novel heating materials can promote significant osteogenesis, and may thus be a promising treatment option for diseases associated with bone defects.
Highlights
Patients with bone defects after resection of bone tumors, complicated fractures, and chronic infections should be adequately treated by specialist physicians
We examined the effect of hyperthermia in two cell lines, osteoblast-like MC3T3 cells and ATDC5, the latter of which shows chondrogenic to osteogenic differentiation
Resovist1 is a hydrophilic colloid of the superparamagnetic iron oxide nanoparticles used for contrast media of Magnetic resonance imaging (MRI) and it can be heated by alternating magnetic fields (AMF) [30]
Summary
Patients with bone defects after resection of bone tumors, complicated fractures, and chronic infections should be adequately treated by specialist physicians. The collection of sufficient autologous bone is occasionally difficult, in children and the elderly. Allograft bone has similar properties to those of autologous bone and is widely used, in western countries, this does not remove risks such as infection, and since there exists no system for organizing the provision of allogenic bone in eastern countries mainly due to religious issues, it is not currently a realistic option. A variety of bone substitutes such as tricalcium phosphate and hydroxyapatite (HA), have been introduced to overcome and/or minimize these disadvantages [3,4], but they have the disadvantage of no or insufficient capacity of osteoinductive ability compared with autologous bone grafts. There is demand for the development of more effective methods for the promotion of osteogenesis
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