Differentiation of mesenchymal stem cells for cartilage tissue engineering: Individual and synergetic effects of three-dimensional environment and mechanical loading

Abstract

Chondrogenesis of dedifferentiated chondrocytes and mesenchymal stem cells is influenced not only by soluble molecules like growth factors, but also by the cell environment itself, through mechanical cues – which act as stimulation factor and influences nutrient transport - and through adhesion to extracellular matrix cues – which determine cell shape. Although the effects of each separate effect are known, few observation and conclusions about the interaction between both of them have been developed. In this work, it is reviewed the state of the art on the single effects between mechanical and biochemical cues, and on the combination between them. Furthermore, a discussion is provided on the existent lack of techniques currently used to determine the mechanical properties of materials and tissues generated in vitro, and the new trends to solve that.This work is funded by European Regional Development Fund through the "Programa Operacional Fatores de Competitividade – COMPETE" and by portuguese national funds arranged by FCT (Fundation for the Science and Technology), project reference PEST- C/FIS/UI607/2014. This work was funded also by the Spanish Ministry of Economy and Copetitiveness (MINECO) through the project MAT2013-46467-C4-1-R (including the FEDER financial support). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors also thank funding from Matepro – “Optimizing Materials and Processes”, ref. NORTE-07-0124-FEDER-000037”, co-funded by the “Programa Operacional Regional do Norte” (ON.2 – O Novo Norte), under the “Quadro de Referência Estratégico Nacional” (QREN), through the FEDER. The authors also thank support from the COST Action MP1206 “Electrospun Nano-fibres for bio inspired composite materials and innovative industrial applications” and MP1301 “New Generation Biomimetic and Customized Implants for Bone Engineering”. Juan Alberto Panadero thanks the FCT for the SFRH/BD/64586/2009 fellowship grant