Osseous Healing with BMP-2

Objectives:  Autogenous bone grafting has been considered ideal for treating craniofacial defects due to its osteoconductive and osteoinductive properties.  Various allograft and xenograft materials are available, but their role is primarily osteoconductive.  Recently, there has been substantial interest in using osteoinductive growth factors as an alternative to traditional grafting.  The powerfully osteoinductive Bone Morphogenic Protein-2(BMP-2) has been shown to successfully stimulate bone formation and has FDA approval for certain oral and maxillofacial bone augmentation procedures using an absorbable collagen sponge (ACS) delivery system.  Regardless of methods employed, it is important to evaluate both the quantity and quality of bone regeneration.  The aim of this study was to evaluate osseous healing in critical-sized rat calvarial defects over a 2-12wk healing period.         

Methods:  Critical-sized defects were made in rat calvaria and filled with either (1) an ACS alone or (2)BMP-2 adsorbed onto an ACS in doses of either 1000ng or 2000ng.  To evaluate healing, rats were euthanized at 2, 4, 8, and 12wks.  Calvariae were evaluated by histology and microCT analysis. 

Results:  The defects treated with BMP-2 at both doses demonstrated increased osseous regeneration over control from 2-12wks.  By 4wks, new bone bridged those defects treated with the 2000ng dose, while defects treated with the 1000ng dose demonstrated significant, but less complete healing.  The presence of woven bone was confirmed by histology at 2wks for each dose, and maturation to lamellar bone was noted by 4wks.  Bone density continued to increase through later time points, with the 1000ng dose approaching similar density to the 2000ng dose by 8wks. 

Conclusions:  The results demonstrate the ability of BMP-2 to quickly induce osseous regeneration in critical-sized defects, with new bone evident by 2wks that matured after 4wks and continued to increase in density over later time points.