Artikel
GDF-5-augmented fibrin glue stimulates a calcified cartilage connecting zone enhancing integration of cartilage scaffolds with bone tissue
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Autoren
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Solvig Diederichs
- Othopädische Universitätsklinik Heidelberg, Forschungszentrum für Experimentelle Orthopädie, Heidelberg, Germany
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Yvonne Renz
- Othopädische Universitätsklinik Heidelberg, Forschungszentrum für Experimentelle Orthopädie, Heidelberg, Germany
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Wiltrud Richter
- Othopädische Universitätsklinik Heidelberg, Forschungszentrum für Experimentelle Orthopädie, Heidelberg, Germany
| Veröffentlicht: | 23. Oktober 2017 |
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Gliederung
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Objectives: Long-term regeneration of cartilage defects often fails because of insufficient integration of cartilage implants into the host tissue. We here investigated whether growth and differentiation factor-5 (GDF-5)-augmented fibrin glue is promising to induce a calcified cartilage-layer enhancing bonding of cartilage-relevant carriers to bone tissue.
Methods: Expanded human bone marrow stromal cells (BMSCs) were embedded in fibrin glue and subjected to in vitro chondrogenesis with TGF-β with or without 150 ng/mL GDF-5 before constructs were implanted subcutaneously into SCID mice. Bonding of cartilage scaffolds to bone was tested in vivo with hydrogel and collagen constructs that were glued onto bone disks with fibrin glue augmented with 900 ng GDF-5.
Results and Conclusion: GDF-5 significantly enhanced ALP activity during in vitro chondrogenesis of BMSCs while ACAN and COL2A1 gene expression and proteoglycan-, collagen-type II- and collagen-type X-deposition remained similar to controls. Pellets pre-treated with GDF-5 mineralized faster in vivo and formed more ectopic bone. In a novel ectopic integration model, GDF-5 strongly supported formation of a calcified cartilage layer increasing bonding of cartilage-relevant carriers with bone tissue (Figure 1 [Fig. 1]).
In conclusion, the pro-chondrogenic and pro-hypertrophic activity makes GDF-5-augmented fibrin an attractive bioactive glue with high potential to increase bonding of cartilage implants to subchondral bone.
