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.

Intestinal anastomotic leaking, which involves the discharge of chemically aggressive, non‐sterile fluids into the abdomen, remains one of the most dreaded postoperative complications of abdominal surgery. Depending on the site and the patient condition, incidence ranging between 4% and 21% and mortality rates up to 27% are reported. Currently available surgical sealants only poorly address the issue, especially since most commonly used fibrin glues fail due to insufficient adhesion and chemical instability. Here, a chemically highly resistive, leak‐tight, and mucoadhesive hydrogel sealant, which is grafted on the surface of the intestinal wall using a mutually interpenetrating network that traverses hydrogel and tissue is presented. In contrast to clinically used fibrin‐based sealants (including Tachosil), the developed adhesive poly(acrylamide‐methyl acrylate‐acrylic acid) patch does not degrade and exhibits strong tissue adhesion even when exposed to intestinal fluid. The biocompatible hydrogel patch effectively seals anastomotic leaks in ex vivo intestinal models, greatly surpassing commercial sealants (time to patch‐failure >24 h compared to 5 min for commonly used Tachosil). Importantly, the developed adhesive patch paves the way for the application of both mechanically and chemically robust sealants suitable for the treatment and prevention of intestinal leaks.

Wound care and soft tissue repair have been a major human concern for millennia. Despite considerable advancements in standards of living and medical abilities, difficult-to-heal wounds remain a major burden for patients, clinicians and the healthcare system alike. Due to an aging population, the rise in chronic diseases such as vascular disease and diabetes, and the increased incidence of antibiotic resistance, the problem is set to worsen. The global wound care market is constantly evolving and expanding, and has yielded a plethora of potential solutions to treat poorly healing wounds. In ancient times, before such a market existed, metals and their ions were frequently used in wound care. In combination with plant extracts, they were used to accelerate the healing of burns, cuts and combat wounds. With the rise of organic chemistry and small molecule drugs and ointments, researchers lost their interest in inorganic materials. Only recently, the advent of nano-engineering has given us a toolbox to develop inorganic materials on a length-scale that is relevant to wound healing processes. The robustness of synthesis, as well as the stability and versatility of inorganic nanotherapeutics gives them potential advantages over small molecule drugs. Both bottom-up and top-down approaches have yielded functional inorganic nanomaterials, some of which unite the wound healing properties of two or more materials. Furthermore, these nanomaterials do not only serve as the active agent, but also as the delivery vehicle, and sometimes as a scaffold. This review article provides an overview of inorganic hybrid nanotherapeutics with promising properties for the wound care field. These therapeutics include combinations of different metals, metal oxides and metal ions. Their production, mechanism of action and applicability will be discussed in comparison to conventional wound healing products.