Mesenchymal stem cell-mediated endochondral ossification utilising micropellets and brief chondrogenic priming
1 Department of Oral and Maxillofacial Surgery, Special Dental Care and Orthodontics, Erasmus MC, University Medical Centre, 3000 DR Rotterdam, The Netherlands
2 Department of Genetics, Cancer Genomics Centre, Erasmus MC, 3000 DR Rotterdam, The Netherlands
Abstract
With limited autologous and donor bone graft availability, there is an increasing need for alternative graft substitutes. We have previously shown that chondrogenically priming mesenchymal stem cell (MSC) pellets for 28 din vitrowill reproducibly result in endochondral bone formation afterin vivoimplantation. However, pellet priming time for clinical applications is quite extensive. A micropellet (μpellet)-fibrin construct was developed and coupled, with a shorter priming period, determined by anin vitrotime course experiment.In vitrodata showed expression of chondrogenic genes and matrix production after 7 d of chondrogenic priming, indicating that briefer priming could possibly be used to induce bone formationin vivo. 7 and 28 d primed pellet, pellet-fibrin and μpellet-fibrin constructs were cultured forin vitroanalysis and implanted subcutaneously for 8 weeks into nude mice. μpellet-fibrin constructs, culturedin vitrofor 7 or 28 d, produced comparable bone to standard pelletsin vivo. MSC-mediated bone formation was achieved following only 7 d ofin vitropriming. Bone formationin vivoappeared to be influenced by overall matrix production pre-implantation. Given this short priming time and the injectable nature of the μpellet-fibrin constructs, this approach might be further developed as an injectable bone substitute, leading to a minimally-invasive treatment option, which would allow for tailored filling of bone defects.
Keywords
- Bone tissue engineering
- endochondral ossification
- fibrin
- mesenchymal stem cells
- hydrogel
- bone
- micropellet
- chondrogenesis
- marrow
- injectable
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