Gene expression of upregulated/hypomethylated identified in integrative methylome and transcriptome analysis (Turner et al., 2019b). (a) Heatmap representation of the temporal change in gene expression in bioengineered SkM at 0.5, 3, and 24 h post‐loading. Fold‐change was determined via relativizing gene expression in loaded to non‐loaded muscle for each separate timepoint (0.5, 3, or 24 h, as indicated on the x‐axis). The color intensity represents the level of fold‐change in gene expression (as indicated on the right y‐axis). Upregulated/hypomethylated genes are in order (from top to bottom) of the largest (MSN) to smallest (ADCY3) increase in gene expression at 3 h post‐loading. (b) Gene expression of upregulated/hypomethylated genes identified in Turner et al., (2019b) were compared between loaded bioengineered SkM at 3 h only (clear circles), when all timepoints (0.5, 3, and 24 h) were pooled (diamonds) and after acute RE in humans (clear triangles) and programmed RT in rodents (bold triangles). Bold circles with errors represent mean ± SEM when all models/timepoints of exercise/loading were pooled. *Indicates a significant difference between loaded bioengineered SKM at 3 h and human acute RE. &Indicates significant difference between mean expression of pooled timepoints (0.5, 3, and 24 h) in loaded bioengineered SkM and human acute RE. #Indicates significant difference between loaded bioengineered SKM and RT in rodents. Temporal gene expression profile (0.5, 3, and 24 h) in loaded versus non‐loaded bioengineered SkM alone for genes associated with (c) actin/ECM structure and remodeling (d) mechano‐transduction, muscle protein synthesis (MPS) and TGF‐β/calcium/IL‐6/retinoic acid signaling, and (e) tumor suppression, histone methylation, coagulation and angiogenesis identified in Turner et al., (2019b). *Depicts significant change in gene expression after loading relative to non‐loaded bioengineered muscle at the same timepoint. n = 5 replicate cultures/constructs per condition (loaded/non‐loaded) and timepoint (0.5, 3, and 24 h). All data is presented as mean ± SEM. IL, interleukin; RE, resistance exercise; RT, resistance training; SkM, skeletal muscle; TGF, tumor growth factor