Stimulation of a calcified cartilage connecting zone by GDF‐5‐augmented fibrin hydrogel in a novel layered ectopic in vivo model. Issue 6 (25th October 2017)

• Record Type: Journal Article
• Authors: Diederichs, Solvig; Renz, Yvonne; Hagmann, Sébastien; Lotz, Benedict; Seebach, Elisabeth; Richter, Wiltrud
• Is Part Of: Journal of biomedical materials research. Volume 106:Issue 6(2018)
• Page Start: 2214
• Page End: 2224
• Publication Date: 2017-10-25
• Subjects: GDF‐5 -- mesenchymal stromal cells -- chondrogenesis -- calcified cartilage -- fibrin hydrogel; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/jbm.b.34027
• Languages: English
• ISSNs: 1552-4973

Abstract

Abstract: Tissue engineering approaches for reconstructing full‐depth cartilage defects need to comprise a zone of calcified cartilage to tightly anchor cartilage constructs into the subchondral bone. Here, we investigated whether growth and differentiation factor‐5‐(GDF‐5)‐augmented fibrin hydrogel can induce a calcified cartilage‐layer in vitro that seamlessly connects cartilage‐relevant biomaterials with bone tissue. Human bone marrow stromal cells (BMSCs) were embedded in fibrin hydrogel and subjected to chondrogenesis with TGF‐β with or without GDF‐5 before constructs were implanted subcutaneously into SCID mice. A novel layered ectopic in vivo model was developed and GDF‐5‐augmented fibrin with BMSCs was used to glue hydrogel and collagen constructs onto bone disks to investigate formation of a calcified cartilage connecting zone. GDF‐5 significantly enhanced ALP activity during in vitro chondrogenesis while ACAN and COL2A1 mRNA, proteoglycan‐, collagen‐type‐II‐ and collagen‐type‐X‐deposition remained similar to controls. Pellets pretreated with GDF‐5 mineralized faster in vivo and formed more ectopic bone. In the novel layered ectopic model, GDF‐5 strongly supported calcified cartilage formation that seamlessly connected with the bone. Pro‐chondrogenic and pro‐hypertrophic activity makes GDF‐5‐augmented fibrin an attractive bioactive hydrogel with high potential to stimulate a calcified cartilage connecting zone in situ that might promote integration of cartilage scaffolds with bone. Thus, GDF‐5‐augmented fibrin hydrogel promises to overcome poor fixation of biomaterials in cartilage defects facilitating their long‐term regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2214–2224, 2018.