Thiol-functionalized polylysine as macro antibacterial thiol-norbornene crosslinker for constructing 3D-bioprinted wound healing scaffolds

A new strategy to synthesize norbornene-modified gelatin (GelNB) was introduced by utilizing norbornene-2-carboxylic anhydride. The synthesized GelNB showed great compatibility with positively charged thiolate ε- Polylysine (PLSH). • Compared with the GelMA or GelNB/DTT, the developed GelNB/PLSH exhibited superior photo-crosslinking reactivity, bioactivity, and printability. • Both GelNB/PLSH solution and hydrogel exhibited broad-spectrum antibacterial ability without the addition of any antibacterial additives. • The rat adipose-derived stem cells (ADSCs)-laden GelNB/PLSH scaffolds enhanced the wound healing outcomes of full-thickness skin defects. Photo-crosslinking-based 3D bioprinting is a promising approach to fabricate bioactive cell-laden scaffolds for wound healing. While thiol-ene-based bioink has been developed to fabricate 3D devices with improved gelation and bioactivity, the bacterial contamination remains a threat to further application. To address this problem, we have introduced a strategy to modify ε-Polylysine (ε-PL) with thiol groups (PLSH) and combine it with norbornene-modified gelatin (GelNB). The GelNB/PLSH bioink not only holds robust photo-crosslinking reactivity but also exhibits superior antibacterial capacity. The GelNB/PLSH hydrogel showed rapid photo-crosslinking rate, tunable physicochemical properties, improved bioactivity, favorable biocompatibility, and good printability. The GelNB/PLSH antibacterial bioink, along with rat adipose-derived stem cells (rADSCs), can be used to construct 3D scaffolds that promote full-thickness skin defects healing in rats. Overall, this study preliminarily prove the potential of GelNB/PLSH as an antibacterial bioink for wound healing and tissue engineering.