Stiffness-controlled three-dimensional collagen scaffolds for differentiation of human Wharton's jelly mesenchymal stem cells into cardiac progenitor cells

Stem cell‐based regenerative therapy has emerged as a promising treatment for myocardial infarction. The aim of this study is to develop stiffness‐controlled collagen scaffolds to allow proliferation and differentiation of mesenchymal stem cell (MSCs) into cardiac progenitor cells. In this study transforming growth factor β2 (TGF‐β2), was used to induce stem cell differentiation into cardiac lineage cells. Collagen scaffolds were cross‐linked with cross‐linkers, 1‐Ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC), and N‐Hydroxysuccinimide (NHS). The results showed that collagen scaffolds cross‐linked with 25/50 and 50/50 of EDC mM/NHS mM cross‐linkers exhibited little difference in shape and size, the scaffold cross‐linked with 50/50 of cross‐linkers demonstrated better interconnectivity and higher Young's modulus (31.8 kPa) than the other (15.4 kPa). SEM observation showed that MSCs could grow inside the scaffolds and interact with collagen scaffolds. Furthermore, greater viability and cardiac lineage differentiation were achieved in MSCs cultured on stiffer scaffolds. The results suggest that three‐dimensional type I collagen scaffolds with suitable cross‐linking to adjust for stiffness can affect MSC fate and direct the differentiation of MSCs into cardiac progenitor cells with/without TGF‐β2. These stiffness‐controlled collagen scaffolds hold great potential as carriers for delivering MSCs differentiated cardiac progenitor cells into infracted hearts. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2234–2242, 2016.