Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional (3D) encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular-traction, independent of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that either permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). In addition, switching the permissive hydrogel to a restrictive state via delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Also, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.

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Biological processes are dynamic in nature, and growing evidence suggests that matrix stiffening is particularly decisive during development, wound healing and disease; yet, nearly all in vitro models are static. Here we introduce a step-wise approach, addition then lightmediated crosslinking, to fabricate hydrogels that stiffen (for example, ~3-30 kPa) in the presence of cells, and investigated the short-term (minutes-to-hours) and long-term (daysto-weeks) cell response to dynamic stiffening. When substrates are stiffened, adhered human mesenchymal stem cells increase their area from ~500 to 3,000 µm 2 and exhibit greater traction from ~1 to 10 kPa over a timescale of hours. For longer cultures up to 14 days, human mesenchymal stem cells selectively differentiate based on the period of culture, before or after stiffening, such that adipogenic differentiation is favoured for later stiffening, whereas osteogenic differentiation is favoured for earlier stiffening.

Three-dimensional (3D) printing is becoming an increasingly common technique to fabricate scaffolds and devices for tissue engineering applications. This is due to the potential of 3D printing to provide patient-specific designs, high structural complexity, rapid on-demand fabrication at a low-cost. One of the major bottlenecks that limits the widespread acceptance of 3D printing in biomanufacturing is the lack of diversity in “biomaterial inks”. Printability of a biomaterial is determined by the printing technique. Although a wide range of biomaterial inks including polymers, ceramics, hydrogels and composites have been developed, the field is still struggling with processing of these materials into self-supporting devices with tunable mechanics, degradation, and bioactivity. This review aims to highlight the past and recent advances in biomaterial ink development and design considerations moving forward. A brief overview of 3D printing technologies focusing on ink design parameters is also included.

Hydrogels with controlled surface patterns are useful for a range of applications, including in microdevices, sensors, coatings, and adhesives. In this work, a simple and robust method to generate a wide range of osmotically driven surface patterns, including random, lamellar, peanut, and hexagonal structures is developed. This method does not require the use of organic solvents for swelling, pre‐patterning of the film surface, or coating of a second layer on the gel. The patterns are fabricated by exposing a photocurable formulation to light while open to air and then swelling, using oxygen inhibition of the radical polymerization at the surface to create a gradient of crosslinking with depth, which was confirmed by measuring the double bond conversion at the surface, surface mechanics, and molecule diffusion into the network. The modulus gradient, and hence osmotic pressure, is controlled by the crosslinker concentration, and the characteristic size of the patterns is determined by the initial film thickness. The patterns are stable in both swollen and dry states, creating a versatile approach that is useful for diverse polymers to create complex patterns with long‐range order.