Addressing multidrug-resistant microbial infections linked to implantable biomedical devices is an urgent need. In recent years, there has been an active exploration of different surface coatings to prevent and combat drug-resistant microbes. In this research, we present a facile chemical modification of thermoplastic polyurethane (TPU) surfaces with poly(ethylene glycol)-based recombinant human α-defensin 5 (HD5) protein with antimicrobial activity. TPU is one of the most relevant materials used for medical devices with good mechanical properties but also good chemical resistance, which makes it difficult to modify. The chemical modification of TPU surfaces is achieved via a three-step procedure based on (i) TPU activation using hexamethylene diisocyanate (HDI); (ii) interfacial reaction with poly(ethylene glycol) (PEG) derivatives; and finally, (iii) a facile click reaction between the PEG-maleimide terminated assembled monolayers on the TPU and the cysteine (-thiol) termination of the recently designed recombinant human α-defensin 5 (HD5) protein.

The obtained PEG based HD5 assembled monolayers on TPU were characterized using a surface science multitechnique approach including scanning electron microscopy, atomic force microscopy, contact angle, and X-ray photoelectron spectroscopy. The modified TPU surfaces with the HD5 protein derivative exhibit broad-spectrum antibacterial properties reducing biofilm formation against Pseudomonas aeruginosa (Gram-negative), methicillin-resistant Staphylococcus aureus (MRSA) (Gram-positive) and methicillin-resistant Staphylococcus epidermidis (MRSE) (Gram-positive). These findings underscore the substantial potential of protein-modified TPU surfaces for applications in combating bacterial infections associated with implantable materials and devices.