Functional Peptides: Comparing Synthetic and Sequence-Engineered Antibiofilm Pharmaceutics

Biofilm formation is a complex phenomenon employed by microbes to counteract antimicrobials. Biofilm-associated infections are a challenging threat to modern medicine. Antimicrobial peptides (AMPs) are recognized as some of the most promising therapeutics to tackle biofilm-producing and multidrug-resistant (MDR) pathogens. However, stability, toxicity, and potency are key issues in the case of naturally occurring AMPs. Next-generation antibiofilm tools, such as synthetic or engineered AMPs, have emerged as a potent therapeutic choice. Synthetic peptides offer structural simplicity, versatility for chemical modification, and increased stability, which makes them capable of effectively disrupting both the biofilm matrix and the bacterial membrane. For engineered peptides, rational sequence modification, hybridization, and computational design are used to overcome limitations related to selectivity, biofilm-specific targeting and regulatory pathway modulation. This review provides a critical evaluation of synthetic and engineered AMPs from various perspectives, such as design strategies, antibiofilm action mechanisms, therapeutic performance, and translational potential. This study sheds light on current advances and emerging technologies, including AI-guided peptide optimization and multifunctional peptide platforms, and thereby sets the stage for the rational development of peptide-based therapeutics aimed at overcoming biofilm-mediated antimicrobial resistance (AMR).