Handheld bioprinter-enabled in situ application of lignin-mediated green-synthesized AgNP-doped antibacterial GelMA-silk fibroin tissue adhesives: In vitro and ex vivo characterizations.

Tissue adhesives offer a rapid, suture-sparing strategy for achieving conformal sealing on irregular and wet tissue surfaces; however, their controlled in situ application and simultaneous antibacterial functionality remain important challenges. Handheld bioprinters (biopens) address the need for easy application of tissue adhesives that can be applied quickly and in situ to irregular wound surfaces, cure rapidly with light, and simultaneously reduce the risk of infection. In this study, biopen-compatible, photocurable, and multifunctional tissue adhesives were developed by integrating lignin-mediated, green-synthesized silver nanoparticles (L-AgNPs) into a gelatin methacryloyl-silk fibroin (GSF) matrix. The resulting formulations were readily extruded through the biopen and applied in situ onto porcine skin defects, where light curing formed a tissue-adherent barrier that provided effective sealing. Ex vivo adhesion tests on porcine skin demonstrated high adhesive performance and mechanical integrity, with the optimal formulation exhibiting a burst pressure of 1019.06 ± 126.90 mmHg for dry and 986.77 ± 45.55 mmHg for wet conditions, a lap-shear adhesive force of 12.59 ± 2.16 N, and a wound closure adhesive strength of 1.26 ± 0.17 MPa. In vitro evaluations using human dermal fibroblasts (HDFs) confirmed the biocompatibility of the adhesives, and the addition of L-AgNPs imparted antibacterial functionality to the adhesive. Overall, these findings indicate that this biopen-based, in situ applicable GSF/L-AgNP adhesive represents a promising fast-curing and multifunctional platform for tissue sealing applications. Nevertheless, further validation using in vivo wound healing and long-term degradation models is required to fully assess the translational potential.