Micropillar patterns were fabricated and used to study cell adhesion, morphology, and function. Micropillars were produced in poly(2-hydroxyethyl methacrylate (HEMA)/N,N-(dimethylaminoethyl)methacrylate (DMAEMA)/tetraethylene glycol dimethacrylate (TEGDMA)) hydrogels using soft lithography, had dimensions of 1 μm diameter, and were either 2.05 or 4.91 μm tall. The patterned hydrogel substrates increased adhesion and induced the formation of cellular aggregates. Digital micrographs were used to quantify aggregate size and number. Differentiation of hMSCs toward adipocytes and chondrocytes was performed using the respective complete culture and differentiation medium for 2 weeks. Cells were stained for Oil red O, Alcian blue, and Type II collagen. Hydrogel substrates supported the differentiation of hMSCs to adipocytes and chondrocytes. The taller micropillar patterns supported the attachment and growth of larger aggregates and were more amenable to aid chondrogenic differentiation.
Tissue engineering strategies for regenerating damaged cartilage using hydrogels have garnered significant attention due to the limited self-healing capacity of damaged cartilage tissue and the restrictions of current medical treatment methods. In particular, using human mesenchymal stem cells (hMSCs) as the cell source has shown the potential to differentiate along a chondrogenic lineage. Hydrogels, whether made of synthetic polymers, natural polymers, or combinations, are widely explored as scaffolding materials mimicking the natural cartilage environment. Based on the understanding of the importance of surface nanotopographies and mechanical stiffness, hydrogels have been presented in various forms and tested for the differentiation of hMSCs. The primary focus of this review is to provide a summary of recent advances in physically and chemically modified hydrogels promoting the chondrogenesis of hMSCs. Advances in micromachining have helped in forming surfaces with the required roughness or an array of micropillars of defined architecture. Hydrogels have been combined with various stimulants such as small peptides, growth factors, and many modified matrix elements. Creating anisotropic hydrogels mimicking the extracellular matrix of cartilage has also been reported. These studies show promising results and identify a niche for in-vitro differentiation of chondrocytes from hMSCs.
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