Martin T. Matter, Fabian Starsich, Marco Galli, Markus Hilber, Andrea A. Schlegel, Sergio Bertazzo, Sotiris E. Pratsinis, Inge K. Herrmann

Despite decades of research, wound complications remain a major cause of postoperative mortality, especially in the face of multiple comorbidities. Addressing the issue of anastomotic leakages and impaired wound healing from a new angle is of great interest with the prospect of having direct impact on patient outcome. Recently, aqueous suspensions of silica and iron oxide nanoparticles have been employed to connect biological tissue by serving as an adhesive layer eventually leading to macroscopic gluing of tissue. In this work, we explore the prospects of this effect by introducing bioactive tissue adhesives composed of nanoparticles produced via scalable and sterile flame spray pyrolysis. We investigate six different metal oxides on cytocompatibility, hemostatic activity and adhesive properties in a small intestine lap joint model. While bioglass nanoparticles show exceptionally strong procoagulant and adhesive properties, the cell membrane integrity is impaired at high particle concentrations. Interestingly, when bioglass is combined with ceria, a material that has well-documented cytoprotective effects, the resulting hybrid particles exhibit the same beneficiary effects as bioglass while featuring superior cytocompatibility. Taken together, we demonstrate highly modular synthesis of nanoparticles expressing adhesive properties in conjunction with tailored bioactivity. Such bioactive nanoparticles as adhesion nuclei in wound healing have a wide range of potential applications in surgical wound care and regenerative medicine.