Abstract
Gelatin hydrogels can mimic the microenvironments of natural tissues and encapsulate cells homogeneously, which makes them attractive for cartilage tissue engineering. Both the mechanical and biochemical properties of hydrogels can affect the phenotype of chondrocytes. However, the influence of each property on chondrocyte phenotype is unclear due to the difficulty in separating the roles of these properties. In this study, we aimed to study the influence of hydrogel stiffness on chondrocyte phenotype while excluding the role of biochemical factors, such as adhesion site density in the hydrogels. By altering the degree of methacryloyl functionalization, gelatin hydrogels with different stiffnesses of 3.8, 17.1, and 29.9 kPa Young’s modulus were prepared from the same concentration of gelatin methacryloyl (GelMA) macromers. Bovine articular chondrocytes were encapsulated in the hydrogels and cultured for 14 days. The influence of hydrogel stiffness on the cell behaviors including cell viability, cell morphology, and maintenance of chondrogenic phenotype was evaluated. GelMA hydrogels with high stiffness (29.9 kPa) showed the best results on maintaining chondrogenic phenotype. These results will be useful for the design and preparation of scaffolds for cartilage tissue engineering.
Highlights
Cartilage defects are common diseases in our daily life, while the self-healing capacity of cartilage is very limited due to the lack of vasculature for nutrition supply
gelatin methacryloyl (GelMA) hydrogels with higher stiffness were degraded more slowly when compared to those with lower stiffness. These results suggested that the enzymatic degradability of GelMA hydrogels could be controlled by the degree of cross-linking and and remodel the extracellular matrix for cell spreading and migration [42]
All of our results suggested the GelMA hydrogels with high stiffness had the best function for the maintenance of chondrocyte phenotype
Summary
Cartilage defects are common diseases in our daily life, while the self-healing capacity of cartilage is very limited due to the lack of vasculature for nutrition supply. Scaffolds, cells, and growth factors are generally needed for tissue engineering. The interaction between cells and scaffolds plays an important role in controlling cell functions. Many factors can affect the cell-scaffold interaction, such as biological cues and physical cues [2,3]. Biological cues are generally transmitted through the receptors on cell membrane (e.g., integrin) and bioactive molecules in the extracellular matrices, which have been well studied [4,5]. As one of the physical cues, matrix stiffness has been reported to affect cell behaviors, such as cell spreading, migration, proliferation, and differentiation [10,11,12,13]. The matrix stiffness needs to be optimized for different cell types and the cellular response to matrix stiffness should be well studied. The fates of some types of cells, such as fibroblasts [15], neutrophils [16], and mesenchymal stem cells (MSCs) [17], have been
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