Because
of the size of bone substitute material particles, large
animal bone defect models are usually required for the assessment
of these materials. However, these models have several disadvantages
including high cost, complicated operation procedures, ethical issues,
and difficulties in sample analysis. In addition, for mimicking the
bone environment, conventional subcutaneous models require the addition
of osteogenic factors and stem cells, resulting in an expensive model
with a complex experimental procedure. To avoid these issues, in this
study, we proposed a convenient and effective blood prefabrication
subcutaneous small animal model that could be applied to assess bone
substitute materials. Our results demonstrated that blood prefabrication
could be an economical, convenient, and useful “adhesive”
for handling bone substitute particles. This process provided porcine
hydroxyapatite (PHA) with a microenvironment enriched with mesenchymal
stem cells and growth factors. Using this strategy, a bonelike structure
could form in a rat subcutaneous pocket. Furthermore, the optimized
subcutaneous model was used to evaluate the PHA’s osteoinductivity,
producing results similar to those of the calvarial bone defect in
terms of osteogenesis, osteoclastogenesis, and blood vessel formation.
These results collectively imply that the blood prefabrication subcutaneous
small animal model is convenient and effective for the assessment
of osteoinductivity of bone substitute materials.