Complete regeneration of large bone defects in rats with commercially available fibrin loaded with BMP-2
1 Department of Orthopaedics, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands
2 Department of Oral and Maxillofacial Surgery and Special Dental Care, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands
3 Regenerative Medicine Centre Utrecht, Utrecht, the Netherlands
4 Department of Orthopaedics, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands
5 Department of Orthopaedics, Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands
6 Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, the Netherlands
Abstract
This study aimed at investigatingin vitroandin vivothe efficiency of commercially available fibrin as a carrier for controlled and sustained bone morphogenetic protein-2 (BMP-2) release to induce bone formation and reduce the side effects of its use.In vitrorelease and activity of low-dose recombinant human BMP-2 (rhBMP-2) (37.5 µg/mL) embedded in commercially available fibrin were evaluated and, subsequently, critical-size femur defects in rats were grafted to study bone regeneration and vascularisation by micro-computed tomography (µCT) and histology.In vitroexperiments showed a sustained BMP-2 release with a high BMP activity remaining after 28 d.In vivo, fibrin loaded with BMP-2 showed an extremely fast bone healing, with a large amount of new bone formation throughout the entire defect in the first 4 weeks and complete cortical repair and fusion after 8 weeks, with no ectopic bone formation. In contrast, the control fibrin group did not fuse after 12 weeks. Vascularisation was similar in both groups at 4 and 12 weeks after implantation. In conclusion, commercially available fibrin is a very efficient carrier for rhBMP-2 to graft critical-size cortical bone defects and might be a more optimal delivery vehicle for BMP-2-induced bone regeneration than currently available collagen sponges.
Graphical Abstract

Keywords
- Preclinical studies
- non-union
- bone morphogenetic proteins
- bioengineering
- implants
- injury/fracture healing
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