Understanding the (dis)-assembly of in situ forming hydrogel coatings in a 2D model system

Injectable hydrogels are important in situ forming implants for tissue regeneration at damaged sites. Understanding the behavior of these systems in a complex in vivo environment remains a challenge. Ultrathin films as 2D model systems are expected to provide fundamental insights into formation and (bio)degradation at material-liquid interfaces, and are also applicable as bioresponsive coatings.Hydrogel ultrathin films are prepared by covalently cross-linking four-arm PEG macromers with maleimide end-groups (PEG4MAL) at alkaline pH using two different types of dithiol-bearing cross-linkers - thio-depsipeptide (TDP) or 3,6-Dioxa-1,8-octanedithiol (DODT). This thiol-Michael addition "click" reaction is carried out at the air-water interface using the Langmuir technique. Morphological observation in real time is carried out by Brewster angle microscopy (BAM) and in coatings using atomic force microscopy (AFM). Stability against enzymatic and oxidative degradation is evaluated in the same setup.Non-cross-linked PEG or PEG incubated with cross-linkers at slightly acidic pH desorbs from the interface over time. Cross-linking of PEG at alkaline pH renders 2D hydrogel networks (thickness <1 nm) that are stable against desorption. They are easily transferrable onto solid mica surfaces, forming homogenous coatings as revealed by AFM. The type of dithiol cross-linker used to form the branching centers influences the degradability of these 2D hydrogel networks in the presence of lipase, peroxides, or bases. For example, enzymatic degradation of the 2D hydrogel networks can be switched "on" or "off" depending on the cleavable sites in the cross-linkers.