Overall, the use of specific biomaterials/biologicals was more effective than OFD in improving attachment levels in intraosseous defects. Difference in CAL gain varied greatly with respect to different biomaterial/biological agent. Due to a significant heterogeneity in results between studies in most treatment groups, general conclusions about the expected clinical benefit of graft biomaterials/biologicals need to be interpreted with caution. Further research should focus on understanding this variability.