Lysozyme Amyloid Fibril-Integrated PEG Injectable Hydrogel Adhesive with Improved Antiswelling and Antibacterial Capabilities

Hydrogels with inherent antibacterial activities have been attracting increasing attention, particularly for biomedical applications. Biology provides a range of materials and mechanisms to meet diverse requirements for bacterial combating. Lysozyme after fibrillation (LZMF) has a much superior antibacterial ability than globular native lysozyme due to its decreased positive charges and increased hydrophobic beta-sheet component. Here, we propose to design a poly(ethylene glycol) (PEG) cross-linked LZMF composite antibacterial hydrogel by utilizing the nucleophilic substitution reaction between LZMF and N-hydroxysuccinimide end groups on four-arm PEG-NHS. The generated PEG-LZMF hydrogel is bacteria-resistant both in vitro and in vivo as expected and has good biocompatibility. Moreover, the volume expansion of PEG can be significantly inhibited due to the presence of hydrophobic lysozyme amyloid fibrils. In addition, the relatively fast cross-linking reaction can make PEG-LZMF both injectable and shape-compatible. The simultaneous reaction with tissue-exposed -NH2 or -SH also confers a tissue-adhesive ability. We envision that this hydrophobic lysozyme amyloid fibril-integrated PEG composite hydrogel can effectively adhere/protect open wounds and internal incisions and suppress pathogen infection through a biomimetic antibacterial mechanism. Considering the simple fabrication process, this multifunctional PEG-LZMF antibacterial hydrogel is promising for clinical transformation.