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A number of biomaterials have been developed, some of which already enjoy widespread clinic use.
We have devised a new honeycomb tricalcium phosphate (TCP) containing through-and-through
holes of various diameters to control cartilage and bone formation. However, the way in which the
geometric structure of the honeycomb TCP controls cartilage and bone tissue formation separately
remains unknown. In addition, an association has been reported between bone formation and
angiogenesis. Therefore, in the present study, we investigated the relationship between angiogenesis
and various hole diameters in our honeycomb TCP over time in a rat ectopic hard tissue formation
model. Honeycomb TCPs with hole diameters of 75, 300, and 500 µm were implanted into rat
femoral muscle. Next, ectopic hard tissue formation in the holes of the honeycomb TCP was
assessed histologically at postoperative weeks 1, 2, and 3, and CD34 immunostaining was performed
to evaluate angiogenesis. The results showed that cartilage formation accompanied by thin and poor
blood vessel formation, bone marrow-like tissue with a branching network of vessels, and vigorous
bone formation with thick linear blood vessels occurred in the TCPs with 75-µm, 300-µm, and
500-µm hole diameters, respectively. These results indicated that the geometrical structure of the
honeycomb TCP affected cartilage and bone tissue formation separately owing to the induced
angiogenesis and altered oxygen partial pressure within the holes.