## 4 Conclusions  
Changing the inlet flow velocity of a bioreactor is an effective method for regulating WSS in bone tissue repair scaffolds. By adjusting the flow velocity, scaffolds of different structures can achieve proportional scaling (up or down) of the WSS distribution, thereby promoting cell differentiation along different orientations. However, flow velocity regulation cannot alter the pattern of the WSS distribution. During cell perfusion culture, altering the flow orientation enables cells to differentiate along the same direction. Heating can improve the heterogeneity of flow distribution within bone tissue repair scaffolds and enhance their mass transfer efficiency. Due to decreased viscosity of the liquid, heating results in a slight reduction of WSS within the scaffolds.  
Comparative assessment of several scaffold architectures reveals that cylindrical unit cell structures exhibit the highest permeability and superior internal flow uniformity, eliminating WSS concentration. When designing scaffolds, curvilinear geometries should be prioritized to generate multidirectional flow paths, thereby enhancing intra-scaffold flow homogeneity. Crucially, linear collinear pore channels must be avoided, as they create centralized high-velocity flow cores, causing heterogeneous WSS distribution, which may induce cell detachment or death. Among structural parameters, pore diameter (>0.4 mm) represents a primary determinant of permeability, while porosity should exceed 60%. Strategic architectural modification serves as an effective approach for optimizing scaffold-wide WSS distribution.  
This study conducts a comprehensive investigation into the optimization of bone tissue repair scaffolds, analyzing the regulatory mechanisms of unit cell-based scaffolds and proposing a multi-parameter control methodology integrating flow velocity, temperature, and structural design to achieve scaffold optimization. The approach significantly enhances design efficiency while reducing experimental costs, demonstrating substantial practical and economic value. However, the research relies on static cellular response assumptions, whereas actual bone regeneration involves dynamic macrophage-osteoblast-endothelial cell interactions, neglecting impacts of cellular proliferation and mineralization on scaffold structural evolution, which introduces limitations. Future studies should refine computational models by incorporating dynamic cellular feedback mechanisms to improve accuracy  
Figure 26: WSS frequency distribution of S-0.7 scaffold under different temperature control.  
and explore combinatorial arrangements of heterogeneous scaffold architectures beyond the current homogeneous designs to identify novel optimization pathways.  
Conceptualization, Y.Z. and Y.G.; data curation, Y.X.; formal analysis, Y.X.; funding acquisition, Y.G.; investigation, Y.X.; methodology, Y.G.; project administration, Y.Z.; resources, Y.G.; software, Y.X.; supervision, Y.X.; validation, Y.X. and Y.Z.; visualization, Y.X.; writing--original draft, Y.Z.; writing--review and editing, Y.X. All authors have read and agreed to the published version of the manuscript.  
This work was supported by the National Natural Science Foundation of China (grant No. 51606116 and No. 52476212), and the Project of Shanghai Municipal Science and Technology Commission (grant No. 19195810800).  
Not applicable.  
The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.  
The authors declare no conflicts of interest.