Complete regeneration of large bone defects in rats with commercially available fibrin loaded with BMP-2
Open accessAbstract
This study aimed at investigating in vitro and in vivo the 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 vitro release 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 vitro experiments 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.
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Natural polymer carriers may be advantageous if they contain cell binding motifs that promote osteoconductivity.
“Natural polymer carriers may be advantageous if they contain cell binding motifs that promote osteoconductivity. [9–12]”
From Keratin Scaffold Formulation Impacts rhBMP-2 Biodistribution and Bone Regeneration in a Rat Femur Defect Model (2025) · cites this paper as [12]
The Introduction (page unavailable) describes fibrin as a carrier that mimics the natural bone-regeneration environment and provides a favourable setting for cellular attachment and proliferation. It does not identify cell-binding motifs or say that those motifs promote osteoconductivity; the Discussion (page unavailable) instead describes the osteoinductive effect of BMP-containing fibrin. (LLM, conf=0.82)
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References 40 · Cited by 24
- Authors
- Department of Orthopaedics, U. U., Koolen, M., Longoni, A., van der Stok, J., Van der Jagt, O., Gawlitta, D., & Weinans, H.
- Affiliations
- Utrecht University (NL)
- Corresponding author
- Koolen, M
- Venue
- European Cells and Materials
- Publisher
- Forum Multimedia Publishing LLC
- Published
- 2019-09-17
- Volume
- 38
- Pages
- 94-105
- ISSN
- 1473-2262 (ISSN-L)
- OpenAlex
- W2974286856
- Cited by
- 24
- References
- 40
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 5
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- European Cells and Materials (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Health Sciences › Medicine › Epidemiology › Bone fractures and treatments
- Keywords
- BMP-2, fibrin, BMP-2 delivery, sustained drug release, bone regeneration, critical-size bone defect, cortical bone defect, vascularization, ectopic bone formation, collagen sponge, bone grafting
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Femoral Fractures, Femur, Humans, Fibrin Tissue Adhesive, Fracture Healing, Rats, Wistar, Bone Substitutes, Neovascularization, Physiologic, Hydrogels, Mice, Rats, Bone Morphogenetic Protein 2, Drug Liberation
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