Bioenergetic Materials for Tissue Regeneration: Modulating Metabolism to Promote Cellular Anabolism.

Tissue regeneration is an energy-demanding process that requires adequate ATP production to support cellular proliferation, biosynthesis, and tissue remodeling. Under pathological and age-related conditions, bioenergetic deficits impair intrinsic regenerative capacity by disrupting mitochondrial function, redox homeostasis, and anabolic signaling. Although conventional scaffold- and cell-based bioengineering strategies have advanced regenerative medicine, they generally do not directly address the metabolic dysfunction that limits tissue repair. Recently, bioenergetic materials (BEMs) have emerged as a novel class of biomaterials engineered to modulate cellular metabolism in situ. By supplying tricarboxylic acid (TCA) cycle intermediates, delivering metabolic enzymes, or incorporating oxygen-releasing and energy-harvesting components, BEMs replenish cellular ATP, restore redox balance, and activate anabolic signaling pathways that support tissue regeneration. In this review, we classify BEMs according to their principal mechanisms of action and summarize recent advances in their application to bone, cartilage, skin, and neural tissue repair. We further discuss the major challenges to clinical translation and highlight future opportunities for integrating metabolic modulation with advanced fabrication techniques and smart, feedback-regulated biomaterial systems. By reshaping the local metabolic microenvironments, BEMs represent a promising strategy to enhance tissue regeneration in pathological settings characterized by mitochondrial dysfunction, redox imbalance, inflammation, and insufficient energy supply.