Stiffness modification of photopolymerizable gelatin-methacrylate hydrogels influences endothelial differentiation of human mesenchymal stem cells

Abstract

For stem cell differentiation, the microenvironment can play an important role, and hydrogels can provide a three-dimensional microenvironment to allow native cell growth in vitro. A challenge is that the stem cell's differentiation can be influenced by the matrix stiffness. We demonstrate a low-toxicity method to create different stiffness matrices, by using a photopolymerizable gelatin methacrylate (GelMA) hydrogel cross-linked by blue light (440 nm). The stiffness and porosity of GelMA hydrogel is easily modified by altering its concentration. We used human bone marrow mesenchymal stem cells (MSCs) as a cell source and cultured the GelMA-encapsulated cells with EGM-2 medium to induce endothelial differentiation. In our GelMA blue light hydrogel system, we found that MSCs can be differentiated into both endothelial-like and osteogenic-like cells. The mRNA expressions of endothelial cell markers CD31, von Willebrand factor, vascular endothelial growth factor receptor-2, and CD34 were significantly increased in softer GelMA hydrogels (7.5% and 10%) compared with stiffer matrices (15% GelMA). On the other hand, the enhancements of osteogenic markers mRNA expressions (Alkaline phosphatase (ALP), Runx2, osteocalcin, and osteopontin) were highest in 10% GelMA. We also found that 10% GelMA hydrogel offered optimal conditions for MSCs to form capillary-like structures. These results suggest that the mechanical properties of the GelMA hydrogel can influence both endothelial and osteogenic differentiation of MSCs and sequent capillary-like formation.

The Influence of Astaxanthin on the Proliferation of Adipose-derived Mesenchymal Stem Cells in Gelatin-Methacryloyl (GelMA) Hydrogels

“…Also in other studies, it has been demonstrated that major carotenoids including astaxanthin, carotene, lutein, zeaxanthin and lycopene stimulate gap junctional intercellular communication, changing the phosphorylation pattern of connexin [35,36]. This could be attributed to the presence of astaxanthin in a three-dimensional hydrogel which induces improved cell-cell communication, thus exhibiting a desirable trait in three-dimensional scaffolds that mimics in vivo environments [18,19].…”

“…Promising results have been observed, in particular, with stem cell proliferation, cellular migration and viability, as it mimics the natural extracellular matrix (ECM) by providing a suitable niche and microenvironment. Many studies in tissue engineering and regenerative medicine have shown that stem cells encapsulated in three-dimensional GelMA scaffolds can be used for the treatment of various diseases and have exhibited positive impacts [17,18,19,20]. Among the various stem cell types, adipose-derived mesenchymal stem cells (ADMSCs) display superior properties over other stem cells, namely: Easy isolation, minimal invasiveness, great safety, no immune rejection with autologous cells and a self-renewal capacity [21,22].…”

Live reporting for hypoxia: Hypoxia sensor–modified mesenchymal stem cells as in vitro reporters

“…Stiffness, pore size, and crosslinking method are significant factors when choosing the most appropriate hydrogel for a specific experiment. GelMA hydrogels are a popular 3D cultivation platform since they show great tunability, allow for cell adhesion via the presence of RGD motifs, and can be modulated by the cells over time (Lin, Su, Lee, & Lin, 2018; Visser et al, 2015; Xiao et al, 2019). In our experiments, we chose a hydrogel concentration of 5% GelMA (w/v), as it has been shown before that MSCs maintain high viability and display spreading at this concentration (Nichol et al, 2010).…”

New-generation osteoplastic materials based on biological and synthetic matrices

“…и персульфат-иона позволяет ковалентно сшивать богатые тирозином белки (резин, желатин, фибриноген) за счет образования дитирозиновых связей и получать биополимерные материалы обладающие варьируемыми биомеханическими и тканеадгезионными свойствами, задаваемыми на этапе создания материала [109,110]. Склонность тирозинбогатых белков к самоорганизации полимерных волокон и взаимодействию с белками внеклеточного матрикса, позволяет использовать биополимеры, сшитые таким способом, в качестве хирургических герметиков или систем доставки лекарственных форм [111,112]. Получаемый таким образом фотополимеризуемый желатиновый гидрогель (РН), обладает пористостью, подходящей для его нагрузки наночастицами модифицированного хитозана (NPCS) [103,113].…”