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

Abstract

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.

<p>Biodegradable Nanopolymers in Cardiac Tissue Engineering: From Concept Towards Nanomedicine</p>

“…[53][54][55][56][57][58] Collagen is one of most preferred biodegradable polymers in diverse tissue engineering applications (especially in cardiac tissue engineering) because of its high biocompatibility, biodegradability, hyposensitivity and low toxicity. 32,59 Collagen scaffolds, especially nanofibrous scaffolds, have been investigated for cardiac tissue engineering. In one study, one of the most facile recent techniques for generating nanofibrous scaffolds out of collagen uses an electric field between a grounded collector and polymer solution by Punnoose et al Fluoroalcohols (such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)) were used to produce nanofibrous scaffolds out of collagen type 1, which has been the main choice for the production of collagen-based biomaterials.…”

“…Moreover, mesenchymal stem cells, in these stiffness-controlled collagen scaffolds, were able to proliferate and differentiate into cardiac progenitor cells in the absence or presence of TGF-β2. 32 Another way to improve the mechanical strength of collagen scaffolds is blending collagen with other materials, such as inorganic materials and natural synthetic polymers. 31 In some studies, carbon nanotubes (CNTs), because of their excellent mechanical strength, electrical conductivity, and high aspect ratios were blended with collagen to improve electrical and mechanical strength.…”

Mapping current research and identifying hotspots on mesenchymal stem cells in cardiovascular disease

“…Reviews ranked second, as there were 755 reviews, accounting for 22.900% of the total. The other 8 document types were meeting abstracts (98), editorial materials (55), book chapters (35), proceedings papers (32), early access (20), letters (5), corrections (3), and news items (1).…”

“…It studied elastic polyurethane nanofiber [29], copolymerization material [30], nano cellulose patch [31], and 3D biomaterial [32] to promote integration of MSCs and myocardial tissue. Scaffolds explored nanofiber scaffold [33,34], collagen scaffold [35], alginate scaffold [36], biomatrix scaffolds [36,37], and porous polysaccharidebased scaffold [38]. Extracellular matrix discussed decellularized bovine myocardial extracellular matrix-based films(dMEbF) [39], synthetic extracellular matrix mimic hydrogel [40], cardiac fibroblast-derived 3D extracellular matrix [41], and porcine small intestinal submucosal extracellular matrix [42] enhanced functions of MSC.…”

Mesenchymal Stem Cells as a Promising Cell Source for Integration in Novel In Vitro Models

“…Other scaffolds have been developed to enhance cardiac differentiation of MSCs, such as PCL [ 98 , 99 , 100 ] and collagen [ 101 , 102 ]; these approaches demonstrated relatively higher yield compared with the methods based on biological factors alone.…”