Data-driven volumetric printing of biomimetic hydrogels enables control of interstitial flow and shear stress

Bone mesoscale architecture governs interstitial fluid dynamics, which regulate cell mechanotransduction and subsequent bone remodelling. However, how trabecular mesoscale features influence fluid flow and wall shear stress (WSS) conducive to osteogenesis remains poorly understood, particularly in osteoporotic bone. This study aims to clarify how osteoporosis-driven architectural deterioration alters fluid-induced mechanical cues and how these cues can be transferred into biomimetic models that enable in vitro investigation of cellular mechanobiological responses. Synchrotron radiation micro-computed tomography (SRμCT) datasets of human trabecular bone were used to extract key morphometric descriptors. Osteoporosis led to reduced bone volume fraction, increased trabecular spacing and higher anisotropy. These parameters informed a Voronoi-based design strategy to generate porous architectures with controlled mesoscale features. Scaffolds were fabricated via Xolography: a dual-colour volumetric printing process. Among four hydrogel formulations varying in ratios of polytheylene glycol diacrylate (PEGDA) and polyethylene glycol dimethacrylate (PEGDMA) which were functionalised with arginine-glycine-aspartic acid (RGD) peptides post-printing, the 30% w/w PEGDA and 10% w/w PEGDMA blend provided the best balance between processability and biological performance measured by metabolic activity. Computational fluid dynamics simulations under perfusion conditions demonstrated that architectural parameters directly govern permeability WSS, enabling access to osteogenic-relevant regimes at inlet velocities of 0.15–0.25 mm/s. The resulting scaffolds exhibited permeability values (3.54 × 10⁻⁸–19.0 × 10⁻⁸ m²) comparable to native bone, while distinct architectural configurations produced systematic variations in surface WSS. In particular, structures derived from osteoporotic morphologies displayed higher permeability but reduced WSS, highlighting the strong coupling between geometry and flow-mediated mechanical stimuli. These trends were consistent with simulations performed on native bone volumes, confirming the ability of the approach to preserve condition-specific flow signatures. Herein, this research establishes a data-driven design-to-fabrication strategy for volumetrically printed hydrogels, enabling programmable control of transport properties and shear stress.