A Quantitative Evaluation of the Efficacy of Endochondral Ossification-Based Grafts in Bone Defect Regeneration: An Analysis of Animal Studies

The regeneration of bone defects through bone grafts primarily depends on two strategies: intramembrane ossification (IO) and endochondral ossification (EO). Traditional bone tissue engineering has focused on mimicking the IO process to stimulate the formation of a bone-like matrix. However, repair strategies based on IO often result in excessive deposition of the matrix on the graft surface, hindering bone tissue regeneration. In recent years, researchers have increasingly focused on investigating the reparative potential of EO-based grafts for bone defects, such as microspheres, pellets, and hydrogel. However, the effectiveness of EO-based grafts on bone defects has not yet been quantitatively evaluated. Therefore, this study conducted a systematic review and meta-analysis of previous studies to quantitatively assess the bone regenerative potential of EO-based grafts. The results revealed that EO-based grafts showed favorable ability for bone regeneration. However, there was no significant difference in bone regeneration between EO-based grafts that utilized chondrogenic differentiation or hypertrophic differentiation. Additionally, the results demonstrated low quality in the experimental methods and the reporting of animal studies as well as a low quality of evidence provided by the included studies. Based on this, we propose three suggestions to enhance the quality of experimental methods and reporting in animal experiments. Furthermore, it is essential to conduct more evidence-based research to establish reliable evidence for the clinical application of EO-based grafts.