Development of an Antimicrobial Peptide SAAP-148-Functionalized Supramolecular Coating on Titanium to Prevent Biomaterial-Associated Infections

Titanium implants are widely used in medicine but have a risk of biomaterial-associated infection (BAI), of which traditional antibiotic-based treatment is affected by resistance. Antimicrobial peptides (AMPs) are used to successfully kill antibiotic-resistant bacteria. Herein, a supramolecular coating for titanium implants is developed which presents the synthetic antimicrobial and antibiofilm peptide SAAP-148 via supramolecular interactions using ureido-pyrimidinone supramolecular units (UPy-SAAP-148GG). Material characterization of dropcast coatings shows the presence of UPy-SAAP-148GG at the surface. The supramolecular immobilized peptide remains antimicrobially active in dropcast polymer films and can successfully kill (antibiotic-resistant) Staphylococcus aureus, Acinetobacter baumannii, and Escherichia coli. Minor toxicity for human dermal fibroblasts is observed, with a reduced cell attachment after 24 h. Subsequently, a dipcoat coating on titanium implants is developed and tested in vivo in a subcutaneous implant infection mouse model with S. aureus administered locally on the implant before implantation to mimic contamination during surgery. The supramolecular coating containing 5 mol% of UPy-SAAP-148GG significantly prevents colonization of the implant surface as well as of the surrounding tissue, with no signs of toxicity. This shows that supramolecular AMP coatings on titanium are eminently suitable to prevent BAI.