Physical strategies to engineer supramolecular composite hydrogels for advanced biomedical applications

Co-assembly is a key phenomenon in life, playing a significant role in various biological processes. In particular, supramolecular composite hydrogels (SMCHs) form through the incorporation of diverse functionalities, such as small molecules, polymers, peptides, proteins, nanoparticles, metal ions, and carbon nanomaterials via a co-assembly approach. This approach imparts tunable properties to the resulting hydrogels, including mechanical strength, elasticity, porosity, and responsiveness to external stimuli, thereby enhancing their overall performance compared to their individual constituents. The versatile advantages of SMCHs extend their applications to fields such as targeted drug delivery, tissue engineering, and regenerative medicine. This review offers a comprehensive overview of the key design principles and the physical strategies used to transform supramolecular hydrogels (SMHs) into SMCHs. Furthermore, it highlights recent advances in their biomedical applications, including 3D cell culture, antibacterial properties, anti-inflammatory effects, wound healing, cancer therapy, treatment of ocular infections, dental tissue repair, gastric tissue repair, cardiac tissue regeneration, bone regeneration, and disk repair, is systematically highlighted. We aim to provide innovative perspectives and critical insights into the design and development of SMCHs while addressing their current limitations and challenges, with the goal of advancing their practical applications