From Amino Acids to Proteins: Biomolecular Nanostructures as Closed-Loop Platforms for Tissue Engineering and Drug Delivery

Amino acid-based nanostructures represent an emerging class of biomolecular building blocks for next-generation biomaterials. Unlike native amino acids that lack structural complexity and mechanical integrity, their nanostructured forms, such as nanoparticles, nanofibers, nanotubes, hydrogels, peptides, and protein-based self-assemblies, offer a multifunctional scaffold design that actively participates in autonomous tissue repair. This perspective delves into the polar and nonpolar amino acid nanostructures and their roles in autonomous tissue repair through dynamic interactions with the cellular microenvironment, therapeutic delivery, and stimuli-responsiveness. The potential of advanced amino acid nanostructures, such as hydrogels and protein assemblies, is also discussed, as hydrogels provide hydrated, bioactive networks that mimic extracellular matrix functions, while protein nanostructures bring structural precision and inherent bioactivity to regenerative systems. Importantly, in our perspective, we highlight that amino acid nanostructures represent a dual closed-loop framework comprising a functional loop where these materials demonstrate adaptive response by sensing microenvironmental cues as well as a life cycle loop wherein green fabrication methods and biodegradation support sustainability. We believe that this dual functionality positions amino acid nanostructures as state-of-the-art regenerative platforms that integrate biological intelligence with sustainability, hence bridging the gap between material design and clinically translatable therapeutics.