2010   Volume No 19 – pages 72-85

Title: Long-term dynamic loading improves the mechanical properties of chondrogenic mesenchymal stem cell-laden hydrogel

Author: AH Huang, MJ Farrell, M Kim, RL Mauck

Address: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, 36th Street and Hamilton Walk, Philadelphia, PA 19104, USA

E-mail: lemauck@mail.med.upenn.edu

Key Words: Cartilage, tissue engineering, mesenchymal stem cells, chondrogenesis, mechanical stimulation.

Publication date: February 26th 2010

Abstract: Mesenchymal stem cells (MSCs) are an attractive cell source for cartilage tissue engineering given their ability to undergo chondrogenesis in 3D culture systems. Mechanical forces play an important role in regulating both cartilage development and MSC chondrogenic gene expression, however, mechanical stimulation has yet to enhance the mechanical properties of engineered constructs. In this study, we applied long-term dynamic compression to MSC-seeded constructs and assessed whether varying pre-culture duration, loading regimens and inclusion of TGF-beta3 during loading would influence functional outcomes and these phenotypic transitions. Loading initiated before chondrogenesis decreased functional maturation, although chondrogenic gene expression increased. In contrast, loading initiated after chondrogenesis and matrix elaboration further improved the mechanical properties of MSC-based constructs, but only when TGF-beta3 levels were maintained and under specific loading parameters. Although matrix quantity was not affected by dynamic compression, matrix distribution, assessed histologically and by FT-IRIS analysis, was significantly improved on the micro- (pericellular) and macro- (construct expanse) scales. Further, whole genome expression profiling revealed marked shifts in the molecular topography with dynamic loading. These results demonstrate, for the first time, that dynamic compressive loading initiated after a sufficient period of chondro-induction and with sustained TGF-beta exposure enhances matrix distribution and the mechanical properties of MSC-seeded constructs.

Article download: Pages 72-85 (PDF file)
Supplementary file: Table 1 (PDF file)
Supplementary file: Table 2 (PDF file)