Extracellular Matrix-Surrogate Advanced Functional Composite Biomaterials for Tissue Repair and Regeneration.

Native tissues, comprising multiple cell types and extracellular matrix components, are inherently composites. Mimicking the intricate structure, functionality, and dynamic properties of native composite tissues represents a significant frontier in biomaterials science and tissue engineering research. Biomimetic composite biomaterials combine the benefits of different components, such as polymers, ceramics, metals, and biomolecules, to create tissue-template materials that closely simulate the structure and functionality of native tissues. While the design of composite biomaterials and their in vitro testing are frequently reviewed, there is a considerable gap in whole animal studies that provides insight into the progress toward clinical translation. Herein, we provide an insightful critical review of advanced composite biomaterials applicable in several tissues. The incorporation of bioactive cues and signaling molecules into composite biomaterials to mimic the native microenvironment is discussed. Strategies for the spatiotemporal release of growth factors, cytokines, and extracellular matrix proteins are elucidated, highlighting their role in guiding cellular behavior, promoting tissue regeneration, and modulating immune responses. Advanced composite biomaterials design challenges, such as achieving optimal mechanical properties, improving long-term stability, and integrating multifunctionality into composite biomaterials and future directions, are discussed. We believe that this manuscript provides the reader with a timely perspective on composite biomaterials.