Induction of mesenchymal stem cell chondrogenesis by polyacrylate substrates

Abstract

Mesenchymal stem cells (MSCs) can generate chondrocytes in vitro, but typically need to be cultured as aggregates in the presence of transforming growth factor beta (TGF-β), which makes scale-up difficult. Here we investigated if polyacrylate substrates modelled on the functional group composition and distribution of the Arg-Gly-Asp (RGD) integrin-binding site could induce MSCs to undergo chondrogenesis in the absence of exogenous TGF-β. Within a few days of culture on the biomimetic polyacrylates, both mouse and human MSCs, and a mesenchymal-like mouse-kidney-derived stem cell line, began to form multi-layered aggregates and started to express the chondrocyte-specific markers, Sox9, collagen II and aggrecan. Moreover, collagen II tended to be expressed in the centre of the aggregates, similarly to developing limb buds in vivo. Surface analysis of the substrates indicated that those with the highest surface amine content were most effective at promoting MSC chondrogenesis. These results highlight the importance of surface group functionality and the distribution of those groups in the design of substrates to induce MSC chondrogenesis.

A comparative evaluation of the effect of polymer chemistry and fiber orientation on mesenchymal stem cell differentiation

“…Furthermore close cell‐cell contact is essential for successful induction of chondrogenesis of MSCs and the low cell viability on day 1 of MSCs cultured on PLGA suggests reduced cell attachment and thus limited propensity for chondrogenic induction . In addition, it has been suggested that stiffness of the scaffold material may affect differentiation of MSCs by influencing mechanical tension of the cytoskeleton . In particular softer matrices have been found to preferentially induce chondrogenesis of MSCs.…”

Controlled chondrogenesis from adipose-derived stem cells by recombinant transforming growth factor-β3 fusion protein in peptide scaffolds

“…As cell-free implants, peptide scaffolds can be structurally and mechanically similar to cartilage and allow efficient load transfer [35]. In addition, hydrogels may be used to maintain differentiated cells in a given area, or to encourage proliferation of chondrocytes as a technique for regeneration enhancement by encouraging cell migration [36].…”

Polymers, scaffolds and bioactive molecules with therapeutic properties in osteochondral pathologies: what’s new?

“…Moreover, scaffolds can incorporate additional functions such as specific nanotopographies, protein coatings or chemical conjugation of specific signaling molecules. Some examples are the use of polyacrylate substrates that induce chondrogenesis of MSCs by itself, in the absence of any chondrogenic inductor, by the action and distribution of integrin-binding Arg-Gly-Asp (RGD) motif in the surface [91] or the controlled release of TGF-β factors encapsulated, immobilized or merged in the scaffolds that have proved to induce chondrogenic differentiation of MSCs [76,92,93].…”