Biomaterial-Derived Multimodal Cell-Regulatory Signals for Tissue Regeneration

In tissue engineering and regenerative medicine, biomaterials have transitioned from passive structural supports to dynamic platforms capable of actively modulating regenerative microenvironments. Their tunable physical and chemical properties, combined with the capacity for controlled release of bioactive signals or extrinsic stimuli, allow precise regulation of stem, immune, and tissue-specific cell behaviors. However, single-modality of signal remains insufficient to recapitulate the multifactorial and spatiotemporally coordinated processes underlying complex tissue regeneration. From a biomaterial perspective, we proposed biomaterial-based multimodal tissue engineering strategy, focusing on the synergy of multimodal cell-regulatory signals for enhanced tissue regeneration. These multifunctional biomaterials serve as advanced artificial regenerative niches, capable of delivering coordinated multimodal signals to precisely guide cellular behavior and tissue formation. Inspired by bionic design principles, decoding the compositional, structural, mechanical, and biological parameters of the native extracellular matrix-and elucidating their regulatory effects and molecular mechanisms on cellular activities-has informed the development of multifunctional biomaterials for tissue regeneration. Key material properties-spanning mechanical, topological, biochemical, and dynamic characteristics-can be strategically engineered to function as distinct yet complementary regulatory signals in this multimodal approach.