2024-06-13
Natural proteins/peptides possess important biological functions and are widely studied for biomedical and tissue engineering applications. However, their drawbacks such as intolerance to enzymatic degradation, expensiveness and difficulty for large-scale synthesis limit the practical application. We hypothesize that synthetic polymers can mimic the sequence defined natural peptides to obtain important biological functions. We establish water-tolerant, fast and controllable polymerization method for convenient and scalable synthesis of amino acid polymers. By introducing unnatural amino acids, the resulting polymers resist proteolysis and have stable biological functions. Our recent studies demonstrate that our polymeric strategy is valid to mimic different types of natural peptides. By mimicking extra cellular matrix peptides, we discover amino acid polymers that promote osteoblast adhesion comparable to the gold standard RGD peptide, and show excellent in vivo bone repair function. By mimicking host defense peptide (HDP), we find polymers that have potent activity against drug-resistant bacteria and drug-resistant fungi, as well as low hemolysis and low cytotoxicity. The optimal antimicrobial polymers are comparable to, or even superior to, the performance of current antimicrobial drugs both in vitro and in vivo. Notably, these HDP-mimicking polymers don’t cause resistance in bacteria and fungi after continuous use. These studies indicate that peptide-mimicking polymers can have a wide range of applications as the next generation bioactive materials.
