The effect of SDF-1 on low dose BMP-2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model

The treatment of critical size bone defects represents a challenge. The growth factor bone morphogenetic protein 2 (BMP-2) is clinically established but has potentially adverse effects when used at high doses. The aim of this study was to evaluate if stromal derived factor-1 alpha (SDF-1) and BMP-2 released from heparinized mineralized collagen type I matrix (MCM) scaffolds have a cumulative effect on bone regeneration. MCM scaffolds were functionalized with heparin, loaded with BMP-2 and/or SDF-1 and implanted into a murine critical size femoral bone defect (control group, low dose BMP-2 group, low dose BMP-2+SDF-1 group, and high dose BMP-2 group). After 6 weeks, both the low dose BMP-2+SDF-1 group (5.8 +/- 0.6 mm(3), p=0.0479) and the high dose BMP-2 group (6.5 +/- 0.7 mm(3), p=0.008) had a significantly increased regenerated bone volume compared to the control group (4.2 +/- 0.5 mm(3)). There was a higher healing score in the low dose BMP-2+SDF-1 group (median grade 8; Q1-Q3 7-9; p=0.0357) than in the low dose BMP-2 group (7; Q1-Q3 5-9) histologically. This study showed that release of BMP-2 and SDF-1 from heparinized MCM scaffolds allows for the reduction of the applied BMP-2 concentration since SDF-1 seems to enhance the osteoinductive potential of BMP-2. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2126-2134, 2016.