eCM (Eur Cell Mater / e Cells & Materials) Not-for-profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2017   Volume No 34 – pages 142-161

Title: Mesenchymal stem cell-mediated endochondral ossification utilising micropellets and brief chondrogenic priming

Authors: CA Knuth, J Witte-Bouma, Y Ridwan, EB Wolvius, E Farrell

Address:   Department of Oral and Maxillofacial Surgery, Special Dental Care and Orthodontics, Erasmus MC, University Medical Centre, 3000 DR Rotterdam, The Netherlands.

E-mail: e.farrell at

Key Words: Bone tissue engineering, endochondral ossification, fibrin, mesenchymal stem cells, hydrogel, bone, micropellet, chondrogenesis, marrow, injectable.

Publication date: September 22nd 2017

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 d in vitro will reproducibly result in endochondral bone formation after in vivo implantation. 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 an in vitro time course experiment. In vitro data 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 formation in vivo. 7 and 28 d primed pellet, pellet-fibrin and μpellet-fibrin constructs were cultured for in vitro analysis and implanted subcutaneously for 8 weeks into nude mice. μpellet-fibrin constructs, cultured in vitro for 7 or 28 d, produced comparable bone to standard pellets in vivo. MSC-mediated bone formation was achieved following only 7 d of in vitro priming. Bone formation in vivo appeared 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.

Article download: Pages 142-161 (PDF file)