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

2014   Volume No 28 – pages 82-97

Title: Induction of mesenchymal stem cell differentiation and cartilage formation by cross-linker-free collagen microspheres

Author: M Mathieu, S Vigier, M-N Labour, C Jorgensen, E Belamie, D Noël

Address: Inserm U 844, Hôpital Saint-Eloi, INM, 80 Avenue Augustin Fliche, F-34091 Montpellier cedex 5, France

E-mail: marc.mathieu at

Key Words: Biomaterial, cartilage engineering, chondrogenesis, collagen, injectable, mesenchymal stem cell, microspheres, safety, self-assembly, transforming growth factor-β.

Publication date: September 2nd 2014

Abstract: Because of poor self-healing ability, joint cartilage can undergo irreversible degradation in the course of various diseases or after injury. A promising approach for cartilage engineering consists of using of mesenchymal stem cells (MSC) and a differentiation factor combined with an injectable carrier biomaterial. We describe here a novel synthesis route for native collagen microspheres that does not involve the use of potentially toxic crosslinking agents. An emulsion was formed between a type I collagen solution and perfluorinated oil, stabilised by a biocompatible triblock perfluorinated copolymer surfactant. Spherical microparticles of fibrillar collagen were formed through a sol-gel transition induced by ammonia vapours. Electron microscopy observations showed that these self-cross-linked microspheres were constituted by a gel of striated collagen fibrils. Microspheres that were loaded with transforming growth factor beta (TGF-β)3 progressively released this differentiation factor over a four weeks period. Human MSC rapidly adhered to TGF-β3-loaded microspheres and, after 21 d of culture, exhibited typical chondrocyte morphology and produced an uncalcified matrix made of the predominant cartilage components, aggrecan and type II collagen, but devoid of the hypertrophic marker type X collagen. Subcutaneous co-injection of MSC and TGF-β3-loaded microspheres in mice consistently led to the formation of a cartilage-like tissue, which was however hypertrophic, calcified and vascularised. In conclusion, we developed cross-linker free collagen microspheres that allowed chondrogenic differentiation of MSC in vitro and in vivo.

Article download: Pages 82-97 (PDF file)
DOI: 10.22203/eCM.v028a07