To develop hydrogels with high mechanical strength for cell encapsulation and three-dimensional culture is a critical challenge for cartilage tissue engineering. In this study, novel double network (DN) hydrogels were fabricated and phosphate buffer solution (PBS) was used as the solvent to facilitate cell encapsulation. The tough DN hydrogels were prepared through a two-step photopolymerization using neutral oligo(2,2-dimethyltrimethylene carbonate)–poly(ethylene glycol)–oligo(2,2-dimethyltrimethylene carbonate)–diacrylate (DPD–DA) chains for the first network and methacrylated hyaluronic acid (HA–GMA) chains for the second network. The fracture stress values of the optimized and cell-laden DN hydrogels were 8.38 ± 0.67 MPa and 6.28 ± 1.26 MPa, respectively, which showed comparable mechanical strength with natural articular cartilage tissue. The live/dead cell viability assay of cell-laden DN hydrogels demonstrated the tough DN hydrogels have comparable cytocompatibility with PEG hydrogels. After long-term culture, cartilage-specific extra cellular matrix accumulated in these DN hydrogels. The results indicated the potential of the novel DN hydrogels as cartilage tissue engineering scaffolds.

Various cues from the microenvironment in which cells live can regulate cellular functions. In addition to biochemical cues, increasing evidence has demonstrated that mechanical cues (namely, substrate/matrix stiffness in this review) presented by the cell microenvironment are also critically important in regulating cellular functions. However, most studies on stiffness-regulated cellular functions mainly focus on 2D conditions, which might not be able to recapitulate the 3D microenvironment encountered by the cells in vivo. In contrast to the observations in 2D microenvironments, studies have already shown that cells respond differently to mechanical cues under 3D microenvironments. In this review, the mechanisms of cellular mechanosensing and mechanotransduction are briefly presented, followed by the introduction of the most studied 2D/3D platforms. The effects of substrate/matrix stiffness on cellular functions, including cell migration, spreading, proliferation, phenotype, and differentiation, under different dimensionalities are summarized and discussed. Finally, the persisting questions and future outlook are also proposed.

Here, light and ferric ion (Fe³⁺) responsive fluorochromic hydrogels with high strength and self-healing ability were designed and synthesized.