Strategic design of antimicrobial hydrogels containing biomimetic crosslinkers for enhanced matrix responsiveness

Supramolecular nanocomposite materials have emerged as a leading interdisciplinary research area that exploits synergistic relationships at the nanoscale to enhance properties (mechanical and chemical) of next-generation biopolymeric materials. Hydrogels synthesized from natural biopolymers are commonly utilized due to their intrinsic properties such as non-cytotoxicity and biodegradability as well as their well-defined three-dimensional, non-covalent network that is ideal for modification and functionalization. Therefore, it is critical to develop a mechanistic understanding tailored to the interactions of the biopolymer scaffold with the functional additives present in these complex matrices. This work will discuss the strategic design of hydrogels placing emphasis on the selection of the biopolymer network and the critical role that the incorporation of additives, such as biomimetic crosslinking agents (lactones/amino acids) and antimicrobial nanoparticles (NPs), have on the resultant properties of the nanocomposite. Results have shown that the hydrogen bonding capacity of the biomimetic additives and antimicrobial agents (i.e. AgNPs) impacts the packing density of the hydrogel network and therefore modulates the resultant swellability. Furthermore, the addition of Ag-coated TiO₂ nanoparticles (Ag/TiO₂ NPs) and biomimetic additives provided contact-based antimicrobial activity along with enhanced closure rates of simulated wounds in adult human dermal fibroblasts (HDFa).