Hydrogel dimensionality directs mechanics-dependent nascent matrix deposition by tendon fibroblasts

Hydrogel dimensionality reverses how tendon fibroblasts deposit nascent matrix: in 2D, raising elastic modulus from 10 to 25 kPa increases deposition, while in 3D stiffer (~50 kPa) gels reduce it versus 5 and 10 kPa.

• Why it matters: It is unclear how the dimensionality of a mechanical microenvironment regulates deposition of newly synthesized ECM, despite known mechanosensitive remodeling by tendon fibroblasts in vivo and in vitro.
• What they did: Primary mouse tail tendon fibroblasts were cultured on 2D or encapsulated in 3D norbornene-modified hyaluronic acid hydrogels with tunable mechanics, and nascent glycoproteins were quantified using GalNAz metabolic labeling.
• The result: In 2D, increased modulus enhanced cell spreading and YAP nuclear localization, whereas in 3D matrix deposition progressed over time but was lower in ~50 kPa; softer 3D hydrogels showed higher YAP nuclear localization and increased tendon matrisome genes, including tenascin C and collagen type I.