Triply Periodic Minimal Surfaces (TPMS) can mimic the complex architecture of trabecular bone while facilitating controlled fluid transport and cellular colonisation. This study integrates computational fluid dynamics (CFD), laser powder bed fusion (L-PBF), and in vitro cell assays to evaluate the structure-function relationship of four Ti6Al4V TPMS scaffolds informed by Schwartz Primitive (SSC), Lidinoid (LSC), Gyroid (GSC), and Diamond (DSC) featuring 60% porosity. CFD simulations at inlet velocities ranging from 0.001-0.01 m/s revealed architecture-specific permeability ranging from 1.89 × 10 -9 m 2 (DSC) to 4.29 × 10 -9 m 2 (SSC) at low flow rates, with a consistent inverse relationship between flow velocity and permeability (R 2 > 0.99). Mid-plane velocity fields highlighted scaffold-specific vortex formations and nutrient mixing dynamics, with SSC exhibiting pronounced swirling zones, promoting fluid homogenisation. In vitro cytocompatibility assessed via MTT assay on U-2OS osteosarcoma cells showed >85% viability across all geometries after 24 h and >88% after 7 days, with the LSC scaffold exhibiting the most consistent viability (101.8 ± 7.7%) and SSC showing significant improvement over time (87.2 ± 3.3% to 121.4 ± 6.2%, p < 0.015). Immunofluorescence imaging confirmed cell attachment across all architectures, with GSC and DSC supporting uniform cytoskeletal spreading and enhanced cell-pore integration. Degradation studies in PBS at 37°C showed that DSC scaffolds underwent the highest mass loss (4.42% at day 7), correlating with their larger surface area, while pH monitoring suggested early ion release followed by buffering over time. These results demonstrate that scaffold topology significantly impacts permeability, degradation, and biological performance with SSC and GSC emerging as promising 3D printed microenvironments. • Topology-driven TPMS scaffolds fabricated via L-PBF of Ti6Al4V. • SSC scaffold showed highest permeability of 4.29 × 10 -9 m 2 at 0.001 m/s. • <1% scaffold mass loss over 14 days indicates high degradation stability. • >85% cell viability across all geometries; SSC and GSC supported strong attachment. • Integrated CFD, degradation, and cytocompatibility inform rational scaffold design.

The mechanical microenvironment profoundly influences cell behavior, tissue organization, and disease progression. Recent advances in biomechanical imaging and single-cell multi-omics technologies have enabled the exploration of tissue heterogeneity from both physical and molecular perspectives. This review summarizes key biomechanical imaging methods and evaluates their capabilities and limitations. We further discuss computational strategies for predicting mechanical properties and highlight integrative approaches that link these predictions with single-cell/spatial omics data. These integrative strategies will pave the way for mechanobiology-informed precision medicine.