Self-Assembly of Short Peptides and DNA-Based Materials in Precision Biomedical Applications

The spontaneous assembly of molecular components into highly organised and functional nanostructures through non-covalent interactions constitutes a defining aspect of advanced biomaterials design. This thorough study covers current breakthroughs in self-assembling short peptides and DNA-based materials, which represent a transformative frontier in precise medicinal applications. We investigate the fundamental principles governing their self-assembly mechanisms, including hydrogen bonding, van der Waals interactions, electrostatic forces, π-π aromatic stacking, and metal coordination, which collectively enable the formation of responsive and programmable biomaterial platforms. Self-assembled peptide hydrogels display extraordinary adaptability across different biomedical fields. In drug delivery systems, these materials allow controlled, prolonged, and targeted therapeutic release through stimuli-responsive processes activated by pH, temperature, light, redox conditions, and enzyme activity. For anticancer therapy, peptide hydrogels provide specific tumor microenvironment targeting, addressing complex temperature heterogeneity and acidic conditions while supporting combination chemotherapy and immunotherapy techniques. In wound healing applications, these biomaterials accelerate chronic wound repair by replicating the extracellular matrix, enabling sustained growth factor supply, and exhibiting antimicrobial characteristics that prevent infection while encouraging re-epithelialization. Regenerative medicine applications showcase the potential of these materials in bone regeneration, where peptide hydrogels stimulate osteogenic differentiation and hydroxyapatite binding, and in neural regeneration, where they support axonal growth and functional recovery in spinal cord and peripheral nerve injuries. These hydrogels excel as 3D cell culture platforms and stem cell niches, permitting regulated differentiation and transplantation success while retaining cell viability and proliferation. DNA hydrogels give exceptional programmability and molecular recognition capabilities, enabling advanced biosensing applications and multi-modal therapeutic administration. However, problems including nuclease degradation under physiological settings are addressed by creative stabilising solutions including chemical changes, protective coatings, and hybrid system integration. This review highlights the paradigm shift from passive biomaterials to intelligent, adaptive systems that actively participate in therapeutic processes, positioning self-assembled peptide and DNA hydrogels as foundational technologies for next-generation precision medicine, tissue engineering, and regenerative therapeutics.