Material‐Driven Fibronectin Assembly Promotes Maintenance of Mesenchymal Stem Cell Phenotypes

Abstract

6563wileyonlinelibrary.com in order to maintain multipotency. When using MSCs for regenerative medicine, it is important to obtain a suffi cient number of cells that maintain pluripotency without compromising MSC senescence. [ 3,4 ] Material systems that mimic the natural niche environment of MSCs may offer an alternative to the use of complex cocktails of soluble factors used in the culture media. Previous studies show that the cell/material interface plays an essential role on MSC function and differentiation, encompassing promising approaches to manipulate differentiation of stem cells ranging from chemistry, [5][6][7] surface modifi cations, [ 8,9 ] topography, [10][11][12] stiffness, [ 13,14 ] and even dynamic material properties such as stress relaxation. [ 15 ] While we are starting to identify the range of materials properties that can be used to drive stem cell differentiation, there is much left to discover and understand. In addition, cells do not feel the surface of materials directly, but through an intermediate layer of adsorbed proteins. The conformation and distribution of this protein layer will determine integrin binding and the organization of focal adhesions, which in turn will infl uence cell signaling and hence fate. [16][17][18][19][20] Acrylates are common biomaterials with tunable physical properties. [ 21 ] In this work we used substrates that slightly differ in surface chemistry, varying only one methyl group in the side chain-poly(ethyl acrylate) (PEA) and poly(methyl acrylate) (PMA). Using this material system, we have previously demonstrated that this subtle variation in surface chemistry modulates the conformation of adsorbed fi bronectin (FN). Typically, FN adsorbs to synthetic materials in a globular morphology, as it does on PMA. However, on PEA, the FN molecules spontaneously organize into nanonetworks, a process that we have termed material-driven fi bronectin fi brillogenesis. [22][23][24] We hypothesize that these FN nanonetworks assembled on PEA infl uence the behavior of MSCs. In this new report, we have investigated the role of FN nanonetworks on MSC adhesion, differentiation (osteogenic, adipogenic), and growth, by culturing cells in absence of differentiation factors. ResultsWe have used C3H10T1/2 cells, an established murine multipotent mesenchymal stem (mMSC) cell line from 14-to 17-d-old

Engineered microenvironments for synergistic VEGF – Integrin signalling during vascularization

“…FN nanonetworks on PEA promoted cell adhesion and maintenance of stem cell phenotypes in the absence of GFs [20], [39], [40], [41]. PEA driven FN nanonetworks allow efficient GF presentation and we have shown that PEA+FN+BMP-2 increased osteogenic differentiation in MSCs compared with soluble BMP-2 along with bone regeneration in a critical size defect, [22].…”

Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture

“…It has been shown that the adhesion of FN on poly (ethyl acrylate) (PEA) can lead to a spontaneous organization of FN into protein networks. It has also been shown that cell-free material-induced FN fibrillogenesis influences the maintenance and differentiation of stem cells [3,92]. Furthermore, it was described that the FN network has an increased ability to store growth factors [93].…”

Surfaces Mimicking Glycosaminoglycans Trigger Different Response of Stem Cells via Distinct Fibronectin Adsorption and Reorganization

“…8,9,27,29,30 The most studied surface property influencing Fn conformation is the wettability: hydrohpobic surfaces induce material-driven Fn fibrillogenesis, whereas globular conformation is typical for the protein adsorbed on hydrophilic surfaces. 9,10,27,30,31 Our results are in good agreement with these previous reports. All surfaces studied by us are hydrophilic (Table S1) and the AFM analysis indeed revealed the expected formation of aggregates of different sizes on all − OH containing surfaces ( Figure 1D1− 3).…”